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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. 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.

  3. 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.

  4. 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

  5. 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…

  6. 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.

  7. 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.

  8. 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.…

  9. 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.

  10. 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

  11. 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

  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. 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

  15. 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.

  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. 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

  18. 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.

  19. 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

  20. Magnetic resonance imaging of cardiac sarcoidosis: an evaluation of the cardiac segments and layers that exhibit late gadolinium enhancement

    PubMed Central

    Komada, Tomohiro; Suzuki, Kojiro; Ishiguchi, Hiroaki; Kawai, Hisashi; Okumura, Takahiro; Hirashiki, Akihiro; Naganawa, Shinji

    2016-01-01

    ABSTRACT Cardiac sarcoidosis (CS) can cause sudden death, which is the leading cause of mortality in patients with sarcoidosis in Japan. However, it is difficult to diagnose CS because of the lack of a sensitive diagnostic method for the condition. Late gadolinium-enhanced cardiac magnetic resonance (MR) imaging demonstrates improved sensitivity for diagnosing CS. Therefore, it is important to know the late gadolinium-enhancement (LGE) characteristics of CS on cardiac MR images in order to diagnose CS accurately. In this study, we investigated the most common sites of LGE on cardiac MR images in CS. Late gadolinium-enhanced MR images of 9 consecutive patients with CS (obtained between August 2009 and July 2015) were reviewed by two radiologists. The distribution of LGE was evaluated using the American Heart Association 17-segment model of the left ventricle. The LGE in each segment was also classified into 4 patterns according to the myocardial layer in which it occurred (the subepicardial, subendocardial, intramural, and transmural layer patterns). All 9 patients exhibited LGE in their left ventricle, and 70 of 153 (46%) myocardial segments were enhanced. All of the patients displayed LGE in the basal septal wall. The patients' LGE layer patterns were as follows: subepicardial: 40% (28/70), intramural: 30% (21/70), subendocardial: 16% (11/70), and transmural: 14% (10/70). The basal septum wall and subepicardial layer often exhibit LGE on cardiac MR images in CS patients. LGE can be observed in other segments and layers in some cases. PMID:28008199

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  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. 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.

  8. 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.

  9. 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

  10. 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...

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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."

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  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. 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.

  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. 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.

  18. 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.

  19. 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.

  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. 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.

  2. 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.

  3. [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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Cardiac catheterization

    MedlinePlus

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

  9. 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

  10. 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).

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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…

  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. 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…

  4. 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

  5. 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.

  6. 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.

  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. 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.

  10. 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

  11. 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.

  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. 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

  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. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. [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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  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. 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

  6. 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

  7. 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.

  8. 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.

  9. 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 ...

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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....

  15. 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... Eligibility Requirements for Existing Projects Commitment Applications § 200.46 Commitment issuance....

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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).

  7. 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.

  8. 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

  9. 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

  10. [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°.

  11. 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

  12. 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.

  13. 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)

  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. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Arbitrarily Long Relativistic Bit Commitment

    NASA Astrophysics Data System (ADS)

    Chakraborty, Kaushik; Chailloux, André; Leverrier, Anthony

    2015-12-01

    We consider the recent relativistic bit commitment protocol introduced by Lunghi et al. [Phys. Rev. Lett. 115, 030502 (2015)] and present a new security analysis against classical attacks. In particular, while the initial complexity of the protocol scales double exponentially with the commitment time, our analysis shows that the correct dependence is only linear. This has dramatic implications in terms of implementation: in particular, the commitment time can easily be made arbitrarily long, by only requiring both parties to communicate classically and perform efficient classical computation.

  3. 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)

  4. 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.

  5. 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)

  6. 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

  7. 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

  8. 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)

  9. 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.

  10. 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.

  11. 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

  12. 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).

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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…

  6. 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…

  7. 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):…

  8. 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.

  9. 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…

  10. 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:…

  11. 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…

  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. 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…

  14. 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…

  15. 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,…

  16. 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…

  17. 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.

  18. 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…

  19. 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.

  20. 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.

  1. 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 ...

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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...

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 40 CFR 63.75 - Enforceable commitments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... made, and any other emission reduction measures to be used; and (6) A statement of commitment, signed... approval of commitments that have not been approved by December 1, 1993. (g) The control measure... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Enforceable commitments. 63.75...

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  20. 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... 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...

  1. 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...

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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 ...

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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...

  17. 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.

  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. 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

  20. Employee Commitment to Organizations: A Conceptual Review.

    DTIC Science & Technology

    1981-08-01

    7 A A03 357 OREGON UNIV EUGENE GRADUATE SCHOOLSOF MANAGEMENT AND--ETC F/ 5/1 EMPLOYEE COMMITMENT TO ORGANIZATIONS: A CONC PTUAL REVIEW.CU...Management University of Oregon Eugene, Oregon 97403 \\ . ’k. Employee Commitment to Organizations: A Conceptual Review Richard M. Steers, University of...Review. 5 TYPE OF REPORT 8 PERIO’ COVERED .’ Employee Commitment to Organizations: A Concep- ’ tual Review. 6 PERFORMING ORG. REPORT NUMBER 7. AUTHOR(*) 8

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Behcet Disease Presenting With Cardiac and Pulmonary Masses.

    PubMed

    Ng, Ming-Yen; Boutet, Alexandre; Carette, Simon; de Perrot, Marc; Cusimano, Robert James; Nguyen, Elsie Thao

    2015-09-01

    Computed tomography and magnetic resonance imaging features of inflammatory intracardiac and pulmonary masses secondary to Behcet disease have not been well described in the literature. We present a case of Behcet disease, presenting with enhancing cardiac and pulmonary inflammatory masses that mimicked the imaging appearance of metastatic cardiac angiosarcoma. Subsequent magnetic resonance imaging examination showed the mass reduced in size with immunosuppressive therapy. This case highlights the importance of considering Behcet disease in the differential diagnosis for an enhancing cardiac mass.

  6. 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.

  7. Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis.

    PubMed

    Crouser, Elliott D; Ruden, Emily; Julian, Mark W; Raman, Subha V

    2016-08-01

    Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown to enhance cardiac sarcoidosis detection and correlates with increased cardiac arrhythmia risk. This study was conducted to determine if CMR T2 abnormalities and related arrhythmias are reversible following immune suppression therapy. A retrospective study of subjects with cardiac sarcoidosis with abnormal T2 signal on baseline CMR and a follow-up CMR study at least 4 months later was conducted at The Ohio State University from 2011 to 2015. Immune suppression treated participants had a significant reduction in peak myocardial T2 value (70.0±5.5 vs 59.2±6.1 ms, pretreatment vs post-treatment; p=0.017), and 83% of immune suppression treated subjects had objective improvement in cardiac arrhythmias. Two subjects who had received inadequate immune suppression treatment experienced progression of cardiac sarcoidosis. This report indicates that abnormal CMR T2 signal represents an acute inflammatory manifestation of cardiac sarcoidosis that is potentially reversible with adequate immune suppression therapy.

  8. Inhibition of autophagy inhibits the conversion of cardiac fibroblasts to cardiac myofibroblasts

    PubMed Central

    Gupta, Shivika S.; Zeglinski, Matthew R.; Rattan, Sunil G.; Landry, Natalie M.; Ghavami, Saeid; Wigle, Jeffrey T.; Klonisch, Thomas; Halayko, Andrew J.; Dixon, Ian M.C.

    2016-01-01

    The incidence of heart failure with concomitant cardiac fibrosis is very high in developed countries. Fibroblast activation in heart is causal to cardiac fibrosis as they convert to hypersynthetic cardiac myofibroblasts. There is no known treatment for cardiac fibrosis. Myofibroblasts contribute to the inappropriate remodeling of the myocardial interstitium, which leads to reduced cardiac function and ultimately heart failure. Elevated levels of autophagy have been linked to stress-induced ventricular remodeling and other cardiac diseases. Previously, we had shown that TGF-β1 treatment of human atrial fibroblasts both induced autophagy and enhanced the fibrogenic response supporting a linkage between the myofibroblast phenotype and autophagy. We now demonstrate that with in vitro culture of primary rat cardiac fibroblasts, inhibition of autophagy represses fibroblast to myofibroblast phenoconversion. Culturing unpassaged cardiac fibroblasts for 72 hours on plastic tissue culture plates is associated with elevated α-smooth muscle actin (α-SMA) expression. This activation parallels increased microtubule-associated protein 1A/1B-light chain 3 (LC-3β II) protein expression. Inhibition of autophagy with bafilomycin-A1 (Baf-A1) and chloroquine (CQ) in cardiac fibroblasts significantly reduces α-SMA and extracellular domain A fibronectin (ED-A FN) protein vs untreated controls. Myofibroblast cell migration and contractility were significantly reduced following inhibition of autophagy. These data support the possibility of a causal link between cardiac fibroblast-to-myofibroblast phenoconversion and autophagy. PMID:27705938

  9. 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

  10. 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.

  11. 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…

  12. 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…

  13. 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…

  14. 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).…

  15. 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…

  16. 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.

  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. 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…

  19. 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 J; 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.

  20. Cardiac tamponade, constrictive pericarditis, and restrictive cardiomyopathy.

    PubMed

    Goldstein, James A

    2004-09-01

    The pericardium envelopes the cardiac chambers and under physiological conditions exerts subtle functions, including mechanical effects that enhance normal ventricular interactions that contribute to balancing left and right cardiac outputs. Because the pericardium is non-compliant, conditions that cause intrapericardial crowding elevate intrapericardial pressure, which may be the mediator of adverse cardiac compressive effects. Elevated intrapericardial pressure may result from primary disease of the pericardium itself (tamponade or constriction) or from abrupt chamber dilatation (eg, right ventricular infarction). Regardless of the mechanism leading to increased intrapericardial pressure, the resultant pericardial constraint exerts adverse effects on cardiac filling and output. Constriction and restrictive cardiomyopathy share common pathophysiological and clinical features; their differentiation can be quite challenging. This review will consider the physiology of the normal pericardium and its dynamic interactions with the heart and review in detail the pathophysiology and clinical manifestations of cardiac tamponade, constrictive pericarditis, and restrictive cardiomyopathy.

  1. Cardiac xenotransplantation.

    PubMed

    DiSesa, V J

    1997-12-01

    Heart failure is an important medical and public health problem. Although medical therapy is effective for many people, the only definitive therapy is heart transplantation, which is limited severely by the number of donors. Mechanical devices presently are used as "bridges" to transplantation. Their widespread use may solve the donor shortage problem, but at present, mechanical devices are limited by problems related to blood clotting, power supply, and foreign body infection. Cardiac xenotransplantation using animal donors is a potential biologic solution to the donor organ shortage. The immune response, consisting of hyperacute rejection, acute vascular rejection, and cellular rejection, currently prevents clinical xenotransplantation. Advances in the solution of these problems have been made using conventional immunosuppressive drugs and newer agents whose use is based on an understanding of important steps in xenoimmunity. The most exciting approaches use tools of molecular biology to create genetically engineered donors and to induce states of donor and recipient bone marrow chimerism and tolerance in xenogeneic organ recipients. The successful future strategy may use a combination of a genetically engineered donor and a chimeric recipient with or without nonspecific immunosuppressive drugs.

  2. 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…

  3. Amide hydrogens reveal a temperature-dependent structural transition that enhances site-II Ca(2+)-binding affinity in a C-domain mutant of cardiac troponin C.

    PubMed

    Veltri, Tiago; de Oliveira, Guilherme A P; Bienkiewicz, Ewa A; Palhano, Fernando L; Marques, Mayra de A; Moraes, Adolfo H; Silva, Jerson L; Sorenson, Martha M; Pinto, Jose R

    2017-04-06

    The hypertrophic cardiomyopathy-associated mutant D145E, in cardiac troponin C (cTnC) C-domain, causes generalised instability at multiple sites in the isolated protein. As a result, structure and function of the mutant are more susceptible to higher temperatures. Above 25 °C there are large, progressive increases in N-domain Ca(2+)-binding affinity for D145E but only small changes for the wild-type protein. NMR-derived backbone amide temperature coefficients for many residues show a sharp transition above 30-40 °C, indicating a temperature-dependent conformational change that is most prominent around the mutated EF-hand IV, as well as throughout the C-domain. Smaller, isolated changes occur in the N-domain. Cardiac skinned fibres reconstituted with D145E are more sensitive to Ca(2+) than fibres reconstituted with wild-type, and this defect is amplified near body-temperature. We speculate that the D145E mutation destabilises the native conformation of EF-hand IV, leading to a transient unfolding and dissociation of helix H that becomes more prominent at higher temperatures. This creates exposed hydrophobic surfaces that may be capable of binding unnaturally to a variety of targets, possibly including the N-domain of cTnC when it is in its open Ca(2+)-saturated state. This would constitute a potential route for propagating signals from one end of TnC to the other.

  4. Matrix identity and tractional forces influence indirect cardiac reprogramming

    NASA Astrophysics Data System (ADS)

    Kong, Yen P.; Carrion, Bita; Singh, Rahul K.; Putnam, Andrew J.

    2013-12-01

    Heart regeneration through in vivo cardiac reprogramming has been demonstrated as a possible regenerative strategy. While it has been reported that cardiac reprogramming in vivo is more efficient than in vitro, the influence of the extracellular microenvironment on cardiac reprogramming remains incompletely understood. This understanding is necessary to improve the efficiency of cardiac reprogramming in order to implement this strategy successfully. Here we have identified matrix identity and cell-generated tractional forces as key determinants of the dedifferentiation and differentiation stages during reprogramming. Cell proliferation, matrix mechanics, and matrix microstructure are also important, but play lesser roles. Our results suggest that the extracellular microenvironment can be optimized to enhance cardiac reprogramming.

  5. 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

  6. Cardiac amyloidosis imaged by dual-source computed tomography.

    PubMed

    Marwan, Mohamed; Pflederer, Tobias; Ropers, Dieter; Schmid, Michael; Wasmeier, Gerald; Söder, Stephan; Daniel, Werner G; Achenbach, Stephan

    2008-11-01

    The ability of contrast-enhanced CT to detect "late enhancement" in a fashion similar to magnetic resonance imaging has been reported previously. Typical myocardial distribution patterns of "late enhancement" have been described for MRI. The same patterns can be observed in CT imaging, albeit at a lower signal to noise ratio. We report a case of cardiac amyloidosis with a typical pattern of subendocardial, circumferential late enhancement in all four cardiac chambers.

  7. 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.

  8. 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...

  9. 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....

  10. 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....

  11. 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....

  12. Development of Models for Regional Cardiac Surgery Centers

    PubMed Central

    Park, Choon Seon; Park, Nam Hee; Sim, Sung Bo; Yun, Sang Cheol; Ahn, Hye Mi; Kim, Myunghwa; Choi, Ji Suk; Kim, Myo Jeong; Kim, Hyunsu; Chee, Hyun Keun; Oh, Sanggi; Kang, Shinkwang; Lee, Sok-Goo; Shin, Jun Ho; Kim, Keonyeop; Lee, Kun Sei

    2016-01-01

    Background This study aimed to develop the models for regional cardiac surgery centers, which take regional characteristics into consideration, as a policy measure that could alleviate the concentration of cardiac surgery in the metropolitan area and enhance the accessibility for patients who reside in the regions. Methods To develop the models and set standards for the necessary personnel and facilities for the initial management plan, we held workshops, debates, and conference meetings with various experts. Results After partitioning the plan into two parts (the operational autonomy and the functional comprehensiveness), three models were developed: the ‘independent regional cardiac surgery center’ model, the ‘satellite cardiac surgery center within hospitals’ model, and the ‘extended cardiac surgery department within hospitals’ model. Proposals on personnel and facility management for each of the models were also presented. A regional cardiac surgery center model that could be applied to each treatment area was proposed, which was developed based on the anticipated demand for cardiac surgery. The independent model or the satellite model was proposed for Chungcheong, Jeolla, North Gyeongsang, and South Gyeongsang area, where more than 500 cardiac surgeries are performed annually. The extended model was proposed as most effective for the Gangwon and Jeju area, where more than 200 cardiac surgeries are performed annually. Conclusion The operation of regional cardiac surgery centers with high caliber professionals and quality resources such as optimal equipment and facility size, should enhance regional healthcare accessibility and the quality of cardiac surgery in South Korea. PMID:28035295

  13. MiR-1 Overexpression Enhances Ca2+ release and Promotes Cardiac Arrhythmogenesis by Targeting PP2A Regulatory Subunit B56α and Causing CaMKII-Dependent Hyperphosphorylation of RyR2

    PubMed Central

    Terentyev, Dmitry; Belevych, Andriy E.; Terentyeva, Radmila; Martin, Mickey M.; Malana, Geraldine E.; Kuhn, Donald E.; Abdellatif, Maha; Feldman, David S; Elton, Terry S.; Gyorke, Sandor

    2015-01-01

    MicroRNAs are small endogenous noncoding RNAs that regulate protein expression by hybridization to imprecise complementary sequences of target mRNAs. Changes in abundance of muscle-specific microRNA, miR-1, have been implicated in cardiac disease, including arrhythmia and heart failure. However, the specific molecular targets and cellular mechanisms involved in the action of miR-1 in the heart are only beginning to emerge. In this study we investigated the effects of increased expression of miR-1 on excitation-contraction coupling and Ca2+ cycling in rat ventricular myocytes using methods of electrophysiology, Ca2+ imaging and quantitative immunoblotting. Adenoviral-mediated overexpression of miR-1 in myocytes resulted in a marked increase in the amplitude of the inward Ca2+ current, flattening of Ca2+ transients voltage dependency and enhanced frequency of spontaneous Ca2+ sparks while reducing the sarcoplasmic reticulum Ca2+ content as compared with control. In the presence of isoproterenol, rhythmically paced, miR-1-overexpressing myocytes exhibited spontaneous arrhythmogenic oscillations of intracellular Ca2+, events that occurred rarely in control myocytes under the same conditions. The effects of miR-1 were completely reversed by the CaMKII inhibitor KN93. Although phosphorylation of phospholamban was not altered, miR-1 overexpression increased phosphorylation of the ryanodine receptor (RyR2) at S2814 (CaMKII) but not at S2808 (PKA). Overexpression of miR-1 was accompanied by a selective decrease in expression of the protein phosphatase PP2A regulatory subunit B56α involved in PP2A targeting to specialized subcellular domains. We conclude that miR-1 enhances cardiac excitation-contraction coupling by selectively increasing phosphorylation of the L-type and RyR2 channels via disrupting localization of PP2A activity to these channels. PMID:19131648

  14. 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

  15. Multipotent Stem Cells in Cardiac Regeneration

    PubMed Central

    Karra, Ravi; Wu, Sean M.

    2008-01-01

    Summary The potential for stem cells to ameliorate or cure heart diseases has galvanized a cadre of cardiovascular translational and clinical scientists to take a “first-in-man” approach using autologous stem cells from a variety of tissues. However, recent clinical trial data show that when these cells are given by intracoronary infusion or direct myocardial injection, limited improvement in heart function occurs with no evidence of cardiomyogenesis. These studies illustrate the great need to understand the logic of cell-lineage commitment and the principles of cardiac differentiation. Recent identification of stem/progenitor cells of embryological origin with intrinsic competence to differentiate into multiple lineages within the heart offers new possibilities for cardiac regeneration. When combined with developments in nuclear reprogramming and provided that tumor risks and other challenges of embryonic cell transplantation can be overcome, the prospect of achieving autologous, cardiomyogenic, stem cell-based therapy may be within reach. PMID:18307403

  16. Cardiac tamponade (image)

    MedlinePlus

    Cardiac tamponade is a condition involving compression of the heart caused by blood or fluid accumulation in the space ... they cannot adequately fill or pump blood. Cardiac tamponade is an emergency condition that requires hospitalization.

  17. Cardiac conduction system

    MedlinePlus Videos and Cool Tools

    ... cardiac muscle cells in the walls of the heart that send signals to the heart muscle causing it to contract. The main components ... the cardiac conduction system's electrical activity in the heart.

  18. Sudden Cardiac Arrest

    MedlinePlus

    ... from American Heart Association Aneurysms and Dissections Angina Arrhythmia Bundle Branch Block Cardiomyopathy Carotid Artery Disease Chronic ... terms: SCA, sudden cardiac death (SCD), sudden death, arrhythmias, ... ventricular fibrillation, defibrillator, automatic cardiac defibrillator ( ...

  19. What Is Cardiac Rehabilitation?

    MedlinePlus

    ANSWERS by heart Treatments + Tests What Is Cardiac Rehabilitation? A cardiac rehabilitation (rehab) program takes place in a hospital or ... special help in making lifestyle changes. During your rehabilitation program you’ll… • Have a medical evaluation to ...

  20. Depletion of cardiac catecholamine stores impairs cardiac norepinephrine re-uptake by downregulation of the norepinephrine transporter

    PubMed Central

    Kreusser, Michael M.; Lehmann, Lorenz H.; Haass, Markus; Buss, Sebastian J.; Katus, Hugo A.; Lossnitzer, Dirk

    2017-01-01

    In heart failure (HF), a disturbed cardiac norepinephrine (NE) homeostasis is characterized by depleted cardiac NE stores, impairment of the cardiac NE re-uptake by the neuronal norepinephrine transporter (NET) and enhanced cardiac NE net release. Reduced cardiac NE content appears to be caused by enhanced cardiac NE net release from sympathetic neurons in HF, triggered by neurohumoral activation. However, it remains unclear whether reduced NE itself has an impact on cardiac NE re-uptake, independent of neurohumoral activation. Here, we evaluated whether depletion of cardiac NE stores alone can regulate cardiac NE re-uptake. Treatment of Wistar rats with reserpine (5 mg/kg/d) for one (1d) or five days (5d) resulted in markedly reduced cardiac NE content, comparable to NE stores in experimental HF due to pressure overload. In order to assess cardiac NE re-uptake, the specific cardiac [3H]-NE uptake via the NET in a Langendorff preparation was measured. Reserpine treatment led to decreased NE re-uptake at 1d and 5d compared to saline treatment. Expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of the NE synthesis, was elevated in left stellate ganglia after reserpine. Mechanistically, measurement of NET mRNA expression in left stellate ganglia and myocardial NET density revealed a post-transcriptional downregulation of the NET by reserpine. In summary, present data demonstrate that depletion of cardiac NE stores alone is sufficient to impair cardiac NE re-uptake via downregulation of the NET, independent of systemic neurohumoral activation. Knowledge about the regulation of the cardiac NE homeostasis may offer novel therapeutic strategies in HF. PMID:28282374

  1. The impact of psychological empowerment and organizational commitment on Chines nurses' job satisfaction.

    PubMed

    Zhou, Wen-Bin; Ouyang, Yan-Qiong; Qu, Hui

    2014-11-10

    Abstract Background: Research findings have shown that job satisfaction of Chinese nurses is at a low level. Limited studies have focused on the impact of psychological empowerment and organizational commitment on job satisfaction of Chinese nurses. Aims: The aim of this study is to describe job satisfaction, psychological empowerment and organizational commitment of Chinese nurses and to explore the impact of psychological empowerment and organizational commitment on the nurses' job satisfaction. Methods: A total of 726 nurses were recruited in a convenience sample from 10 tertiary hospitals. Data were collected using four questionnaires including Job Satisfaction Survey, Psychological Empowerment Scale, Organizational Commitment Scale and Demographic Questionnaire. Descriptive analysis, correlation and stepwise multiple regression were used for data analysis. Results: Nurses' job satisfaction, psychological empowerment, and organizational commitment were identified at moderate levels. Nurses' job satisfaction and psychological empowerment were significantly different in terms of age and length of service; nurse job satisfaction varied with respect to marital status. Findings further indicated that nurse job satisfaction was positively correlated with psychological empowerment and organizational commitment. Psychological empowerment, organizational commitment, and marital status were significant predicting factors of nurse job satisfaction. Conclusions: This study provides evidence to help nursing managers and health policy-makers to develop intervention programs aimed at enhancing nurse job satisfaction and retaining nurses.

  2. A practical quantum bit commitment protocol

    NASA Astrophysics Data System (ADS)

    Arash Sheikholeslam, S.; Aaron Gulliver, T.

    2012-01-01

    In this paper, we introduce a new quantum bit commitment protocol which is secure against entanglement attacks. A general cheating strategy is examined and shown to be practically ineffective against the proposed approach.

  3. Green Supplier Network Manufacturer Commitment Form

    EPA Pesticide Factsheets

    Online form expressing interest in committing to be a Green Supplier; this form expresses your intent to participate in a confidential Green Suppliers Network assessment, implement recommended environmental improvements and complete a NIST MEP follow-up.

  4. 24 CFR 241.510 - Commitments.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Purchase and Installation of Energy Conserving Improvements, Solar Energy Systems, and Individual Utility... insured. (b) Types of firm commitment. (1) Where the amount of the loan is $250,000 or more, the...

  5. 24 CFR 241.510 - Commitments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Purchase and Installation of Energy Conserving Improvements, Solar Energy Systems, and Individual Utility... insured. (b) Types of firm commitment. (1) Where the amount of the loan is $250,000 or more, the...

  6. 24 CFR 241.510 - Commitments.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Purchase and Installation of Energy Conserving Improvements, Solar Energy Systems, and Individual Utility... insured. (b) Types of firm commitment. (1) Where the amount of the loan is $250,000 or more, the...

  7. 24 CFR 241.510 - Commitments.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Purchase and Installation of Energy Conserving Improvements, Solar Energy Systems, and Individual Utility... insured. (b) Types of firm commitment. (1) Where the amount of the loan is $250,000 or more, the...

  8. 24 CFR 241.510 - Commitments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Purchase and Installation of Energy Conserving Improvements, Solar Energy Systems, and Individual Utility... insured. (b) Types of firm commitment. (1) Where the amount of the loan is $250,000 or more, the...

  9. Green Suppliers Network Supply Chain Commitment Form

    EPA Pesticide Factsheets

    Online form to show your company desires to be a Green Suppliers Network supply chain. Expresses an intent to: commit to engage at least five suppliers to complete an assessment process within a 12-month period and more.

  10. Quantum Bit Commitment with a Composite Evidence

    NASA Astrophysics Data System (ADS)

    Srikanth, R.

    2004-01-01

    Entanglement-based attacks, which are subtle and powerful, are usually believed to render quantum bit commitment insecure. We point out that the no-go argument leading to this view implicitly assumes the evidence-of-commitment to be a monolithic quantum system. We argue that more general evidence structures, allowing for a composite, hybrid (classical quantum) evidence, conduce to improved security. In particular, we present and prove the security of the following protocol Bob sends Alice an anonymous state. She inscribes her commitment b by measuring part of it in the + (for b = 0) or × (for b = 1) basis. She then communicates to him the (classical) measurement outcome Rx and the partmeasured anonymous state interpolated into other, randomly prepared qubits as her evidence-of-commitment.

  11. Higher Education's Commitment to Instructional Improvement Programs

    ERIC Educational Resources Information Center

    Popham, W. James

    1974-01-01

    Supports the contention that current attempts to improve the quality of university instruction represent meagre efforts due to insufficient commitment, and a lack of resources, both in finances and in personnel. (AM)

  12. Cutting planes for the multistage stochastic unit commitment problem

    DOE PAGES

    Jiang, Ruiwei; Guan, Yongpei; Watson, Jean -Paul

    2016-04-20

    As renewable energy penetration rates continue to increase in power systems worldwide, new challenges arise for system operators in both regulated and deregulated electricity markets to solve the security-constrained coal-fired unit commitment problem with intermittent generation (due to renewables) and uncertain load, in order to ensure system reliability and maintain cost effectiveness. In this paper, we study a security-constrained coal-fired stochastic unit commitment model, which we use to enhance the reliability unit commitment process for day-ahead power system operations. In our approach, we first develop a deterministic equivalent formulation for the problem, which leads to a large-scale mixed-integer linear program.more » Then, we verify that the turn on/off inequalities provide a convex hull representation of the minimum-up/down time polytope under the stochastic setting. Next, we develop several families of strong valid inequalities mainly through lifting schemes. In particular, by exploring sequence independent lifting and subadditive approximation lifting properties for the lifting schemes, we obtain strong valid inequalities for the ramping and general load balance polytopes. Lastly, branch-and-cut algorithms are developed to employ these valid inequalities as cutting planes to solve the problem. Our computational results verify the effectiveness of the proposed approach.« less

  13. Cutting planes for the multistage stochastic unit commitment problem

    SciTech Connect

    Jiang, Ruiwei; Guan, Yongpei; Watson, Jean -Paul

    2016-04-20

    As renewable energy penetration rates continue to increase in power systems worldwide, new challenges arise for system operators in both regulated and deregulated electricity markets to solve the security-constrained coal-fired unit commitment problem with intermittent generation (due to renewables) and uncertain load, in order to ensure system reliability and maintain cost effectiveness. In this paper, we study a security-constrained coal-fired stochastic unit commitment model, which we use to enhance the reliability unit commitment process for day-ahead power system operations. In our approach, we first develop a deterministic equivalent formulation for the problem, which leads to a large-scale mixed-integer linear program. Then, we verify that the turn on/off inequalities provide a convex hull representation of the minimum-up/down time polytope under the stochastic setting. Next, we develop several families of strong valid inequalities mainly through lifting schemes. In particular, by exploring sequence independent lifting and subadditive approximation lifting properties for the lifting schemes, we obtain strong valid inequalities for the ramping and general load balance polytopes. Lastly, branch-and-cut algorithms are developed to employ these valid inequalities as cutting planes to solve the problem. Our computational results verify the effectiveness of the proposed approach.

  14. Young children's understanding of joint commitments.

    PubMed

    Gräfenhain, Maria; Behne, Tanya; Carpenter, Malinda; Tomasello, Michael

    2009-09-01

    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 activity, 3-year-olds (n = 24) reacted to the break significantly more often (e.g., by trying to re-engage her or waiting for her to restart playing) than when she simply joined the child's individual activity unbidden. Two-year-olds (n = 24) did not differentiate between these 2 situations. In the second study, 3- and 4-year-old children (n = 30 at each age) were enticed away from their activity with an adult. Children acknowledged their leaving (e.g., by looking to the adult or handing her the object they had been playing with) significantly more often when they had made a joint commitment to act together than when they had not. By 3 years of age, children thus recognize both when an adult is committed and when they themselves are committed to a joint activity.

  15. Job satisfaction and career commitment among Alzheimer's care providers: addressing turnover and improving staff empowerment.

    PubMed

    Coogle, Constance L; Parham, Iris A; Rachel, Colleen A

    2011-11-01

    This study investigated the relation between job satisfaction and career commitment among 262 Alzheimer's care staff working in long-term and community-based care settings. It was anticipated that the results would suggest whether career commitment could be enhanced to positively influence job satisfaction, and conversely, if improvements in job satisfaction might contribute to a deepened sense of vocational empowerment. Participants attended dementia-specific training and completed 2 short work-related questionnaires that measured job satisfaction and career commitment. The results of stepwise regression revealed interrelations between the 2 constructs. Congruence appeared to be reciprocal with respect to the overall scale scores and the intrinsic job satisfaction measure. Unexpected relations appeared in analyses of the extrinsic job satisfaction measure and the career planning subscale. Results are indicative of the fundamental distinction between job satisfaction and career commitment. Implications for efforts to reduce turnover and improve staff empowerment are also considered.

  16. Preconditioning Human Cardiac Stem Cells with an HO-1 Inducer Exerts Beneficial Effects After Cell Transplantation in the Infarcted Murine Heart.

    PubMed

    Cai, Chuanxi; Guo, Yiru; Teng, Lei; Nong, Yibing; Tan, Min; Book, Michael J; Zhu, Xiaoping; Wang, Xiao-Liang; Du, Junjie; Wu, Wen-Jian; Xie, Wei; Hong, Kyung U; Li, Qianhong; Bolli, Roberto

    2015-12-01

    The regenerative potential of c-kit(+) cardiac stem cells (CSCs) is severely limited by the poor survival of cells after transplantation in the infarcted heart. We have previously demonstrated that preconditioning human CSCs (hCSCs) with the heme oxygenase-1 inducer, cobalt protoporphyrin (CoPP), has significant cytoprotective effects in vitro. Here, we examined whether preconditioning hCSCs with CoPP enhances CSC survival and improves cardiac function after transplantation in a model of myocardial infarction induced by a 45-minute coronary occlusion and 35-day reperfusion in immunodeficient mice. At 30 minutes of reperfusion, CoPP-preconditioned hCSCs(GFP+), hCSCs(GFP+), or medium were injected into the border zone. Quantitative analysis with real-time qPCR for the expression of the human-specific gene HLA revealed that the number of survived hCSCs was significantly greater in the preconditioned-hCSC group at 24 hours and 7 and 35 days compared with the hCSC group. Coimmunostaining of tissue sections for both green fluorescent protein (GFP) and human nuclear antigen further confirmed greater hCSC numbers at 35 days in the preconditioned-hCSC group. At 35 days, compared with the hCSC group, the preconditioned-hCSC group exhibited increased positive and negative left ventricular (LV) dP/dt, end-systolic elastance, and anterior wall/apical strain rate (although ejection fraction was similar), reduced LV remodeling, and increased proliferation of transplanted cells and of cells apparently committed to cardiac lineage. In conclusion, CoPP-preconditioning of hCSCs enhances their survival and/or proliferation, promotes greater proliferation of cells expressing cardiac markers, and results in greater improvement in LV remodeling and in indices of cardiac function after infarction.

  17. Faculty commitment to teaching in a research environment: A case study

    NASA Astrophysics Data System (ADS)

    Joseph, Jann Luciana

    The purpose of this research is to describe the environment in which research science faculty commit to teaching. The study is also exploratory as it documents factors affecting faculty commitment, and formative as the intervention allowed science faculty to articulate their philosophy of teaching. Graduate students in the Department responded to early drafts by forming a peer group that has the potential to affect faculty commitment to teaching in a research environment. To study the complex phenomenon of faculty commitment to teaching I employed qualitative methods. I conducted interviews, engaged in extensive participant observation over twelve months, and reviewed many departmental documents. I did an inductive thematic analysis to develop the case, and members of the Department read and responded to the early drafts of this dissertation. The department's history and faculty's perceptions of teaching both play an important role in faculty commitment to teaching. In addition to the historical context of the environment, collaboration with their peers and informal relationships also enhance faculty commitment. Support staff contributions, interactions with graduate students, and administrative actions through tenure and merit increases also influence faculty commitment to teaching. The role of Chair is pivotal as he is positioned to optimize the areas that facilitate faculty commitment to teaching and reduce the impact of inhibiting factors. These inhibitors are time constraints, communications about teaching, and graduate student funding. In research departments, most teaching is in the form of mentoring and advising the graduate student, and when these teaching-related activities conflict with research productivity faculty commitment to teaching is jeopardized.

  18. Cardiac ion channels

    PubMed Central

    Priest, Birgit T; McDermott, Jeff S

    2015-01-01

    Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. At the same time, off-target interactions of drugs with cardiac ion channels can be the cause of unwanted side effects. This manuscript aims to review the physiology and pharmacology of key cardiac ion channels. The intent is to highlight recent developments for therapeutic development, as well as elucidate potential mechanisms for drug-induced cardiac side effects, rather than present an in-depth review of each channel subtype. PMID:26556552

  19. Increasing Medical Practice Team Commitment: Twenty-Five Strategies.

    PubMed

    Hills, Laura

    2016-01-01

    Employee commitment is one of the most important principles of practice man- agement. Yet commitment is delicate; it must be carefully earned, and it can easily deteriorate. This article explores practical strategies the medical practice manager can use to assess, foster, and increase employee commitment. It de- fines commitment and how commitment is manifested in employee attitudes and behavior. It provides a 10-question guide medical practice managers can use to assess employee commitment, and a four-part roadmap that will inspire commitment through leadership. This article also offers 25 hands-on strate- gies to increase employee commitment, and more than a dozen questions to guide difficult conversations with employees when their commitment level to the medical practice is low or unclear. Finally, this article suggest four drivers of employee commitment and a five-part strategy medical practice managers can use to model commitment through their own leadership.

  20. Human Cardiac Mesenchymal Stromal Cells with CD105+CD34- Phenotype Enhance the Function of Post-Infarction Heart in Mice

    PubMed Central

    Wiśniewska, Ewa; Jarosz-Biej, Magdalena; Smolarczyk, Ryszard; Cichoń, Tomasz; Głowala-Kosińska, Magdalena; Śliwka, Joanna; Garbacz, Marcin; Szczypior, Mateusz; Jaźwiec, Tomasz; Langrzyk, Agnieszka; Zembala, Michał; Szala, Stanisław

    2016-01-01

    Aims The aim of the present study was to isolate mesenchymal stromal cells (MSC) with CD105+CD34- phenotype from human hearts, and to investigate their therapeutic potential in a mouse model of hindlimb ischemia and myocardial infarction (MI). The study aimed also to investigate the feasibility of xenogeneic MSCs implantation. Methods and Results MSC isolated from human hearts were multipotent cells. Separation of MSC with CD105+CD34- phenotype limited the heterogeneity of the originally isolated cell population. MSC secreted a number of anti-inflammatory and proangiogenic cytokines (mainly IL-6, IL-8, and GRO). Human MSC were transplanted into C57Bl/6NCrl mice. Using the mouse model of hindlimb ischemia it was shown that human MSC treated mice demonstrated a higher capillary density 14 days after injury. It was also presented that MSC administrated into the ischemic muscle facilitated fast wound healing (functional recovery by ischemic limb). MSC transplanted into an infarcted myocardium reduced the post-infarction scar, fibrosis, and increased the number of blood vessels both in the border area, and within the post-infarction scar. The improvement of left ventricular ejection fraction was also observed. Conclusion In two murine models (hindlimb ischemia and MI) we did not observe the xenotransplant rejection. Indeed, we have shown that human cardiac mesenchymal stromal cells with CD105+CD34- phenotype exhibit therapeutic potential. It seems that M2 macrophages are essential for healing and repair of the post-infarcted heart. PMID:27415778

  1. Enhancing the [13C]bicarbonate signal in cardiac hyperpolarized [1-13C]pyruvate MRS studies by infusion of glucose, insulin and potassium.

    PubMed

    Lauritzen, Mette Hauge; Laustsen, Christoffer; Butt, Sadia Asghar; Magnusson, Peter; Søgaard, Lise Vejby; Ardenkjær-Larsen, Jan Henrik; Åkeson, Per

    2013-11-01

    A change in myocardial metabolism is a known effect of several diseases. MRS with hyperpolarized (13)C-labelled pyruvate is a technique capable of detecting changes in myocardial pyruvate metabolism, and has proven to be useful for the evaluation of myocardial ischaemia in vivo. However, during fasting, the myocardial glucose oxidation is low and the fatty acid oxidation (β-oxidation) is high, which complicates the interpretation of pyruvate metabolism with the technique. The aim of this study was to investigate whether the infusion of glucose, insulin and potassium (GIK) could increase the myocardial glucose oxidation in the citric acid cycle, reflected as an increase in the [(13)C]bicarbonate signal in cardiac hyperpolarized [1-(13)C]pyruvate MRS measurements in fasted rats. Two groups of rats were infused with two different doses of GIK and investigated by MRS after injection of hyperpolarized [1-(13)C]pyruvate. No [(13)C]bicarbonate signal could be detected in the fasted state. However, a significant increase in the [(13)C]bicarbonate signal was observed by the infusion of a high dose of GIK. This study demonstrates that a high [(13)C]bicarbonate signal can be achieved by GIK infusion in fasted rats. The increased [(13)C]bicarbonate signal indicates an increased flux of pyruvate through the pyruvate dehydrogenase enzyme complex and an increase in myocardial glucose oxidation through the citric acid cycle.

  2. Controlled Cardiac Computed Tomography

    PubMed Central

    Wang, Chenglin; Liu, Ying; Wang, Ge

    2006-01-01

    Cardiac computed tomography (CT) has been a hot topic for years because of the clinical importance of cardiac diseases and the rapid evolution of CT systems. In this paper, we propose a novel strategy for controlled cardiac CT that may effectively reduce image artifacts due to cardiac and respiratory motions. Our approach is radically different from existing ones and is based on controlling the X-ray source rotation velocity and powering status in reference to the cardiac motion. We theoretically show that by such a control-based intervention the data acquisition process can be optimized for cardiac CT in the cases of periodic and quasiperiodic cardiac motions. Specifically, we formulate the corresponding coordination/control schemes for either exact or approximate matches between the ideal and actual source positions, and report representative simulation results that support our analytic findings. PMID:23165017

  3. Developing competence in cardiac care through the use of blended learning: course members' and mentors' accounts.

    PubMed

    Iley, Karen; McInulty, Lorna; Jones, Ian; Yorke, Janelle; Johnson, Martin

    2011-05-01

    The use of blended learning to develop the clinical knowledge and skills of healthcare professionals is increasing. This paper reports the qualitative findings from an evaluation of a blended learning course designed to equip registered nurses with the knowledge and skills required to practice competently in cardiac nursing. The aims of the study were to explore whether a cardiac care course could be successfully delivered mainly online and it had any impact on the students' clinical practice. The sample consisted of course members and their mentors. Data were obtained through focus groups and interviews and analysed using thematic analysis. All students felt they had benefited from undertaking the course. Mentors identified higher levels of confidence and greater depth of knowledge and skills amongst their students. Areas identified for further development by both groups were firstly, the preparation of mentors for their role in supporting the students undertaking an online course and secondly, the expected level of competence that students needed to display in practice. This study indicates online learning is useful in enhancing student competence but may be wrongly seen as requiring less time commitment for both course members and mentors when compared to taught courses.

  4. Sevoflurane Post-conditioning Enhanced Hippocampal Neuron Resistance to Global Cerebral Ischemia Induced by Cardiac Arrest in Rats through PI3K/Akt Survival Pathway

    PubMed Central

    Wang, Zhihua; Ye, Zhi; Huang, Guoqing; Wang, Na; Wang, E.; Guo, Qulian

    2016-01-01

    The purpose of this current study was to evaluate whether improvement of mitochondrial dysfunction was involved in the therapeutic effect of sevoflurane post-conditioning in global cerebral ischemia after cardiac arrest (CA) via the PI3K/Akt pathway. In the first experiment, animals were randomly divided into three groups: a sham group, a CA group, a CA+sevoflurane post-conditioning group (CA+SE). Sevoflurane post-conditioning was achieved by administration of 2.5% sevoflurane for 30 min after resuscitation. Sevoflurane post-conditioning has a significant neuroprotective effect by increasing survival rates and reducing neuronal apoptosis. Additionally, the gene and protein expression of PGC-1α, NRF-1, and TFAM, the master regulators of mitochondrial biogenesis, were up-regulated in the CA+SE group, when compared to the CA group. Similarly, in contrast to the CA group, mitochondria-specific antioxidant enzymes, including heat-shock protein 60 (HSP60), peroxiredoxin 3 (Prx3), and thioredoxin 2 (Trx2) were also increased in the CA+SE group. Finally, administration of sevoflurane ameliorated mitochondrial reactive oxygen species (ROS) formation and maintained mitochondrial integrity. In the second experiment, we investigated the relationship between the PI3K/Akt pathway and mitochondrial biogenesis and mitochondria-specific antioxidant enzymes in sevoflurane-induced neuroprotection. The selective PI3K inhibitor wortmannin not only eliminated the beneficial biochemical processes of sevoflurane by reducing the level of mitochondrial biogenesis-related proteins and aggravating mitochondrial integrity, but also reversed the elevation of mitochondria-specific antioxidant enzymes induced by sevoflurane. Therefore, our data suggested that sevoflurane post-conditioning provides neuroprotection via improving mitochondrial biogenesis and integrity, as well as increasing mitochondria-specific antioxidant enzymes by a mechanism involving the PI3K/Akt pathway. PMID:27965539

  5. Hypoglycemic Effects of Three Medicinal Plants in Experimental Diabetes: Inhibition of Rat Intestinal α-glucosidase and Enhanced Pancreatic Insulin and Cardiac Glut-4 mRNAs Expression.

    PubMed

    Moradabadi, Leila; Montasser Kouhsari, Shideh; Fehresti Sani, Mohammad

    2013-01-01

    Garlic (Allium sativum L., Alliaceae), Persian shallot (Allium ascalonicum L., Alliaceae ) and Sage (Salvia officinalis L., Lamiaceae) are believed to have hypoglycemic properties and have been used traditionally as antidiabetic herbal medicines in Iran. In this study, diabetes was induced by subcutaneous injection of alloxan monohydrate (100 mg kg(-1)) to male Wistar rats. Antidiabetic effects of methanolic extracts of the above mentioned three plants on alloxan-diabetic rats was investigated in comparison with the effects of antidiabetic drugs such as acarbose, glibenclamide and metformin by measuring postprandial blood glucose (PBG), oral glucose tolerance test (OGTT), inhibition of rat intestinal α-glucosidase enzymes activities and pancreatic Insulin and cardiac Glut-4 mRNAs expression. In short term period, hypoglycemic effects of A. sativum and A. ascalonicum showed significant reduction of PBG similar to glibenclamide (5 mg kg(-1) bw) while S. officinalis significantly reduced PBG similar to acarbose (20 mg kg(-1) bw). After 3 weeks of treatment by methanolic plant extracts, significant chronic decrease in the PBG was observed similar to metformin (100 mg kg(-1) bw). For OGTT, S. officinalis reduced PBG in a similar way as acarbose (20 mg kg(-1) bw). Intestinal sucrase and maltase activities were inhibited significantly by A. sativum, A. ascalonicum and S. officinalis. In addition, we observed increased expression of Insulin and Glut-4 genes in diabetic rats treated with these plants extracts. Up regulation of Insulin and Glut-4 genes expression and inhibition of α-glucosidaseactivities are the two mechanisms that play a considerable role in hypoglycemic action of garlic, shallot and sage.

  6. Sevoflurane Post-conditioning Enhanced Hippocampal Neuron Resistance to Global Cerebral Ischemia Induced by Cardiac Arrest in Rats through PI3K/Akt Survival Pathway.

    PubMed

    Wang, Zhihua; Ye, Zhi; Huang, Guoqing; Wang, Na; Wang, E; Guo, Qulian

    2016-01-01

    The purpose of this current study was to evaluate whether improvement of mitochondrial dysfunction was involved in the therapeutic effect of sevoflurane post-conditioning in global cerebral ischemia after cardiac arrest (CA) via the PI3K/Akt pathway. In the first experiment, animals were randomly divided into three groups: a sham group, a CA group, a CA+sevoflurane post-conditioning group (CA+SE). Sevoflurane post-conditioning was achieved by administration of 2.5% sevoflurane for 30 min after resuscitation. Sevoflurane post-conditioning has a significant neuroprotective effect by increasing survival rates and reducing neuronal apoptosis. Additionally, the gene and protein expression of PGC-1α, NRF-1, and TFAM, the master regulators of mitochondrial biogenesis, were up-regulated in the CA+SE group, when compared to the CA group. Similarly, in contrast to the CA group, mitochondria-specific antioxidant enzymes, including heat-shock protein 60 (HSP60), peroxiredoxin 3 (Prx3), and thioredoxin 2 (Trx2) were also increased in the CA+SE group. Finally, administration of sevoflurane ameliorated mitochondrial reactive oxygen species (ROS) formation and maintained mitochondrial integrity. In the second experiment, we investigated the relationship between the PI3K/Akt pathway and mitochondrial biogenesis and mitochondria-specific antioxidant enzymes in sevoflurane-induced neuroprotection. The selective PI3K inhibitor wortmannin not only eliminated the beneficial biochemical processes of sevoflurane by reducing the level of mitochondrial biogenesis-related proteins and aggravating mitochondrial integrity, but also reversed the elevation of mitochondria-specific antioxidant enzymes induced by sevoflurane. Therefore, our data suggested that sevoflurane post-conditioning provides neuroprotection via improving mitochondrial biogenesis and integrity, as well as increasing mitochondria-specific antioxidant enzymes by a mechanism involving the PI3K/Akt pathway.

  7. Hypoglycemic Effects of Three Medicinal Plants in Experimental Diabetes: Inhibition of Rat Intestinal α-glucosidase and Enhanced Pancreatic Insulin and Cardiac Glut-4 mRNAs Expression

    PubMed Central

    Moradabadi, Leila; Montasser Kouhsari, Shideh; Fehresti Sani, Mohammad

    2013-01-01

    Garlic (Allium sativum L., Alliaceae), Persian shallot (Allium ascalonicum L., Alliaceae ) and Sage (Salvia officinalis L., Lamiaceae) are believed to have hypoglycemic properties and have been used traditionally as antidiabetic herbal medicines in Iran. In this study, diabetes was induced by subcutaneous injection of alloxan monohydrate (100 mg kg−1) to male Wistar rats. Antidiabetic effects of methanolic extracts of the above mentioned three plants on alloxan-diabetic rats was investigated in comparison with the effects of antidiabetic drugs such as acarbose, glibenclamide and metformin by measuring postprandial blood glucose (PBG), oral glucose tolerance test (OGTT), inhibition of rat intestinal α-glucosidase enzymes activities and pancreatic Insulin and cardiac Glut-4 mRNAs expression. In short term period, hypoglycemic effects of A. sativum and A. ascalonicum showed significant reduction of PBG similar to glibenclamide (5 mg kg−1 bw) while S. officinalis significantly reduced PBG similar to acarbose (20 mg kg−1 bw). After 3 weeks of treatment by methanolic plant extracts, significant chronic decrease in the PBG was observed similar to metformin (100 mg kg−1 bw). For OGTT, S. officinalis reduced PBG in a similar way as acarbose (20 mg kg−1 bw). Intestinal sucrase and maltase activities were inhibited significantly by A. sativum, A. ascalonicum and S. officinalis. In addition, we observed increased expression of Insulin and Glut-4 genes in diabetic rats treated with these plants extracts. Up regulation of Insulin and Glut-4 genes expression and inhibition of α-glucosidaseactivities are the two mechanisms that play a considerable role in hypoglycemic action of garlic, shallot and sage. PMID:24250646

  8. The Revised Commitment Inventory: Psychometrics and Use with Unmarried Couples

    ERIC Educational Resources Information Center

    Owen, Jesse; Rhoades, Galena K.; Stanley, Scott M.; Markman, Howard J.

    2011-01-01

    The Commitment Inventory measures interpersonal commitment (dedication) and constraint commitment. Since it was first published, substantial revisions have been made, but there are no published data on the psychometric properties of the new version. Furthermore, little information is available on measuring commitment for unmarried couples. This…

  9. 28 CFR 522.11 - Civil contempt commitments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Civil contempt commitments. 522.11..., CLASSIFICATION, AND TRANSFER ADMISSION TO INSTITUTION Civil Contempt of Court Commitments § 522.11 Civil contempt commitments. Inmates can come into Bureau custody for civil contempt commitments in two ways: (a) The...

  10. Further Exploring the Meaning and Measurement of Career Commitment.

    ERIC Educational Resources Information Center

    Blau, Gary J.

    1988-01-01

    Examined the reliability and validity of a career commitment measure using employees (N=266) of newspaper and insurance companies. Results showed career commitment could be reliably measured and was operationally distinct from job involvement and organizational commitment. Discusses findings in terms of meaning of career commitment. (Author/ABL)

  11. Civil Commitment in the United States

    PubMed Central

    West, Sara G.

    2010-01-01

    This article reviews the academic literature on the psychiatric practice of civil commitment. It provides an overview of the history of involuntary psychiatric hospitalization in the United States—from the creation of the first asylum and the era of institutionalization to the movement of deinstitutionalization. The ethical conflict that the practice of involuntary hospitalization presents for providers, namely the conflict between the ethical duties of beneficence and respect for patient autonomy, is presented. The evolution of the United States commitment standards, from being based on a right to treatment for patients with mental illness to being based on dangerousness, as well as the implications that the changes in commitment criteria has had on patients and society, are discussed. Involuntary hospitalization of patient populations that present unique challenges for psychiatry (e.g., not guilty by reason of insanity acquittees, sex offenders, and individuals with eating disorders, substance use disorders, and personality disorders) is discussed. Finally, an overview of outpatient commitment is provided. By reading this article, one will learn the history of involuntary psychiatric hospitalization in the United States and gain an understanding of the ethical issues that make civil commitment one of the most controversial practices in modern psychiatry. PMID:22778709

  12. Robust Unit Commitment Considering Uncertain Demand Response

    DOE PAGES

    Liu, Guodong; Tomsovic, Kevin

    2014-09-28

    Although price responsive demand response has been widely accepted as playing an important role in the reliable and economic operation of power system, the real response from demand side can be highly uncertain due to limited understanding of consumers' response to pricing signals. To model the behavior of consumers, the price elasticity of demand has been explored and utilized in both research and real practice. However, the price elasticity of demand is not precisely known and may vary greatly with operating conditions and types of customers. To accommodate the uncertainty of demand response, alternative unit commitment methods robust to themore » uncertainty of the demand response require investigation. In this paper, a robust unit commitment model to minimize the generalized social cost is proposed for the optimal unit commitment decision taking into account uncertainty of the price elasticity of demand. By optimizing the worst case under proper robust level, the unit commitment solution of the proposed model is robust against all possible realizations of the modeled uncertain demand response. Numerical simulations on the IEEE Reliability Test System show the e ectiveness of the method. Finally, compared to unit commitment with deterministic price elasticity of demand, the proposed robust model can reduce the average Locational Marginal Prices (LMPs) as well as the price volatility.« less

  13. Robust Unit Commitment Considering Uncertain Demand Response

    SciTech Connect

    Liu, Guodong; Tomsovic, Kevin

    2014-09-28

    Although price responsive demand response has been widely accepted as playing an important role in the reliable and economic operation of power system, the real response from demand side can be highly uncertain due to limited understanding of consumers' response to pricing signals. To model the behavior of consumers, the price elasticity of demand has been explored and utilized in both research and real practice. However, the price elasticity of demand is not precisely known and may vary greatly with operating conditions and types of customers. To accommodate the uncertainty of demand response, alternative unit commitment methods robust to the uncertainty of the demand response require investigation. In this paper, a robust unit commitment model to minimize the generalized social cost is proposed for the optimal unit commitment decision taking into account uncertainty of the price elasticity of demand. By optimizing the worst case under proper robust level, the unit commitment solution of the proposed model is robust against all possible realizations of the modeled uncertain demand response. Numerical simulations on the IEEE Reliability Test System show the e ectiveness of the method. Finally, compared to unit commitment with deterministic price elasticity of demand, the proposed robust model can reduce the average Locational Marginal Prices (LMPs) as well as the price volatility.

  14. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  15. Romantic Relationship Commitment and Its Linkages with Commitment to Parents and Friends during Adolescence

    ERIC Educational Resources Information Center

    De Goede, Irene H. A.; Branje, Susan; van Duin, Jet; VanderValk, Inge E.; Meeus, Wim

    2012-01-01

    This five-wave longitudinal study examines linkages between adolescents' perceptions of romantic relationship commitment and the development of adolescents' perceptions of commitment to parents and friends. A total of 218 early-to-middle adolescents (39.0 percent boys) and 185 middle-to-late adolescents (30.8 percent boys) participated.…

  16. Influence of Teacher Empowerment on Teachers' Organizational Commitment, Professional Commitment and Organizational Citizenship Behavior in Schools

    ERIC Educational Resources Information Center

    Bogler, Ronit; Somech, Anit

    2004-01-01

    The present study focuses on the relationship between teacher empowerment and teachers' organizational commitment, professional commitment (PC) and organizational citizenship behavior (OCB). It examines which subscales of teacher empowerment can best predict these outcomes. The data were collected through a questionnaire returned by a sample of…

  17. Highly Committed Teachers: What Makes Them Tick? A Study of Sustained Commitment

    ERIC Educational Resources Information Center

    Fransson, Göran; Frelin, Anneli

    2016-01-01

    This article focuses on teacher commitment, and particularly on teachers displaying sustained high levels of commitment throughout their teaching careers (over 15 years). Graduates from one Teacher Education programme responded to an open-ended questionnaire conducted on 10 occasions concerning their work as teachers, from graduation in 1993 to…

  18. Landscape Architects and Environmental Concern: An Examination of Attitudes, Verbal Commitment and Actual Commitment.

    ERIC Educational Resources Information Center

    Ruiz, Anita Anne

    Landscape architects have a combination of abilities that have been gained through education and experience that could make their demonstration of environmental concern as citizens very effective. This study assessed the attitudes, verbal commitment, and actual commitment regarding environmental concern held by landscape architects registered and…

  19. Cardiac thrombi mistaken for metastasis in recurrent melanoma.

    PubMed

    Galiuto, Leonarda; Locorotondo, Gabriella; Fedele, Elisa; Danza, Maria L; De Vito, Elena; Masi, Ambra; Favoccia, Carla; Rebuzzi, Antonio G; Crea, Filippo

    2015-01-01

    Intra-cardiac thrombi can be incidentally found in recurrent melanoma and need careful assessment. An 81-year-old woman, with a history of malignant nasopharyngeal melanoma, was evaluated by echocardiography and cardiac magnetic resonance due to the detection of undefined masses localized both in right atrium and ventricle during contrast-enhanced thoraco-abdominal computed tomography.

  20. Organizational identification and commitment: correlates of sense of belonging and affective commitment.

    PubMed

    Dávila, Ma Celeste; Jiménez García, Gemma

    2012-03-01

    The general purpose of this work is to analyze the overlap between organizational identification and commitment. Specifically, our study focuses on the analysis of the differences and similarities between sense of belonging (a dimension of organizational identification) and affective commitment (a dimension of organizational commitment). In order to do this, we analyzed their discriminant validity and raised their relationship with variables that previous research had showed like precedent and subsequent variables of them: value congruence, perceived support, organizational citizenship behavior, and intention to continue in the organization. A total of 292 people at one organization completed surveys measuring the variables previously described. The results showed that sense of belonging and affective commitment are different concepts and they have different relationships with relation to precedent and subsequent variables. Affective commitment seems to be more useful than sense of belonging to predict organizational citizenship behavior aimed at the organization and intention to continue. Some practical implications are described.

  1. 3 CFR - Continuation of the National Emergency With Respect to Persons Who Commit, Threaten to Commit, or...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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..., or support terrorism, pursuant to the International Emergency Economic Powers Act (50 U.S.C....

  2. Contractor and Government: Teamwork and Commitment

    NASA Technical Reports Server (NTRS)

    Griffin, Gerald D.

    1984-01-01

    The assigned topic, "Contractor and Government: Teamwork and Commitment," is a subject about vitally interested. The successes of the U.S. space program were built on such teamwork and commitment. It seems only a short time ago that man's role in space was an unknown quantity. In rapid succession, however, the flights of Shepard, Glenn, and Armstrong demonstrated man's capability to live and travel in space. Consequently, we no longer live with the same awe of space. The success of these joint industry-NASA efforts in achieving our Nation's space goals testifies to the validity of our team's past commitment, management expertise, communications techniques, and teamwork over a period of 25 years. Today, however, We are at the beginning of a new era in space.

  3. Vascular endothelial overexpression of human CYP2J2 (Tie2-CYP2J2 Tr) modulates cardiac oxylipin profiles and enhances coronary reactive hyperemia in mice

    PubMed Central

    Hanif, Ahmad; Edin, Matthew L.; Zeldin, Darryl C.; Morisseau, Christophe; Falck, John R.

    2017-01-01

    Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by cytochrome (CYP) P450 epoxygenases, and to ω-terminal hydroxyeicosatetraenoic acids (HETEs) by ω-hydroxylases. EETs and HETEs often have opposite biologic effects; EETs are vasodilatory and protect against ischemia/reperfusion injury, while ω-terminal HETEs are vasoconstrictive and cause vascular dysfunction. Other oxylipins, such as epoxyoctadecaenoic acids (EpOMEs), hydroxyoctadecadienoic acids (HODEs), and prostanoids also have varied vascular effects. Post-ischemic vasodilation in the heart, known as coronary reactive hyperemia (CRH), protects against potential damage to the heart muscle caused by ischemia. The relationship among CRH response to ischemia, in mice with altered levels of CYP2J epoxygenases has not yet been investigated. Therefore, we evaluated the effect of endothelial overexpression of the human cytochrome P450 epoxygenase CYP2J2 in mice (Tie2-CYP2J2 Tr) on oxylipin profiles and CRH. Additionally, we evaluated the effect of pharmacologic inhibition of CYP-epoxygenases and inhibition of ω-hydroxylases on CRH. We hypothesized that CRH would be enhanced in isolated mouse hearts with vascular endothelial overexpression of human CYP2J2 through modulation of oxylipin profiles. Similarly, we expected that inhibition of CYP-epoxygenases would reduce CRH, whereas inhibition of ω-hydroxylases would enhance CRH. Compared to WT mice, Tie2-CYP2J2 Tr mice had enhanced CRH, including repayment volume, repayment duration, and repayment/debt ratio (P < 0.05). Similarly, inhibition of ω-hydroxylases increased repayment volume and repayment duration, in Tie2-CYP2J2 Tr compared to WT mice (P < 0.05). Endothelial overexpression of CYP2J2 significantly changed oxylipin profiles, including increased EETs (P < 0.05), increased EpOMEs (P < 0.05), and decreased 8-iso-PGF2α (P < 0.05). Inhibition of CYP epoxygenases with MS-PPOH attenuated CRH (P < 0.05). Ischemia caused a decrease in mid

  4. Quantum bit commitment under Gaussian constraints

    NASA Astrophysics Data System (ADS)

    Mandilara, Aikaterini; Cerf, Nicolas J.

    2012-06-01

    Quantum bit commitment has long been known to be impossible. Nevertheless, just as in the classical case, imposing certain constraints on the power of the parties may enable the construction of asymptotically secure protocols. Here, we introduce a quantum bit commitment protocol and prove that it is asymptotically secure if cheating is restricted to Gaussian operations. This protocol exploits continuous-variable quantum optical carriers, for which such a Gaussian constraint is experimentally relevant as the high optical nonlinearity needed to effect deterministic non-Gaussian cheating is inaccessible.

  5. Intelligence, democracy, and international environmental commitment.

    PubMed

    Obydenkova, Anastassia; Salahodjaev, Raufhon

    2016-05-01

    This paper investigates the determinants of nations' commitment to environmental protection at the international level by focusing on the role of national intelligence and the level of democracy. The national intelligence is measured by nation's IQ scores. The findings based on a sample of 152 nations provide strong evidence that intelligence has statistically significant impact on ratification of international environmental agreements, and the countries with IQ 10-points above global average are 23% more likely to sign multilateral environmental agreements than others. The findings also demonstrate that it is the combination of high-level of intelligence of nations and democracy, that likely result in international environmental commitments.

  6. Secure quantum bit commitment against empty promises

    SciTech Connect

    He Guangping

    2006-08-15

    The existence of unconditionally secure quantum bit commitment (QBC) is excluded by the Mayers-Lo-Chau no-go theorem. Here we look for the second-best: a QBC protocol that can defeat certain quantum attacks. By breaking the knowledge symmetry between the participants with quantum algorithm, a QBC protocol is proposed and is proven to be secure against a major kind of coherent attacks - the dummy attack, in which the participant makes an empty promise instead of committing to a specific bit. Therefore it surpasses previous QBC protocols which are secure against individual attacks only.

  7. TNF receptor signaling inhibits cardiomyogenic differentiation of cardiac stem cells and promotes a neuroadrenergic-like fate.

    PubMed

    Hamid, Tariq; Xu, Yuanyuan; Ismahil, Mohamed Ameen; Li, Qianhong; Jones, Steven P; Bhatnagar, Aruni; Bolli, Roberto; Prabhu, Sumanth D

    2016-11-01

    Despite expansion of resident cardiac stem cells (CSCs; c-kit(+)Lin(-)) after myocardial infarction, endogenous repair processes are insufficient to prevent adverse cardiac remodeling and heart failure (HF). This suggests that the microenvironment in post-ischemic and failing hearts compromises CSC regenerative potential. Inflammatory cytokines, such as tumor necrosis factor-α (TNF), are increased after infarction and in HF; whether they modulate CSC function is unknown. As the effects of TNF are specific to its two receptors (TNFRs), we tested the hypothesis that TNF differentially modulates CSC function in a TNFR-specific manner. CSCs were isolated from wild-type (WT), TNFR1-/-, and TNFR2-/- adult mouse hearts, expanded and evaluated for cell competence and differentiation in vitro in the absence and presence of TNF. Our results indicate that TNF signaling in murine CSCs is constitutively related primarily to TNFR1, with TNFR2 inducible after stress. TNFR1 signaling modestly diminished CSC proliferation, but, along with TNFR2, augmented CSC resistance to oxidant stress. Deficiency of either TNFR1 or TNFR2 did not impact CSC telomerase activity. Importantly, TNF, primarily via TNFR1, inhibited cardiomyogenic commitment during CSC differentiation, and instead promoted smooth muscle and endothelial fates. Moreover, TNF, via both TNFR1 and TNFR2, channeled an alternate CSC neuroadrenergic-like fate (capable of catecholamine synthesis) during differentiation. Our results suggest that elevated TNF in the heart restrains cardiomyocyte differentiation of resident CSCs and may enhance adrenergic activation, both effects that would reduce the effectiveness of endogenous cardiac repair and the response to exogenous stem cell therapy, while promoting adverse cardiac remodeling.

  8. Cardiac-specific overexpression of caveolin-3 induces endogenous cardiac protection by mimicking ischemic preconditioning

    PubMed Central

    Tsutsumi, Yasuo M.; Horikawa, Yousuke T.; Jennings, Michelle M.; Kidd, Michael W.; Niesman, Ingrid R.; Yokoyama, Utako; Head, Brian P.; Hagiwara, Yasuko; Ishikawa, Yoshihiro; Miyanohara, Atsushi; Patel, Piyush M.; Insel, Paul A.; Patel, Hemal H.; Roth, David M.

    2009-01-01

    Background Caveolae, lipid-rich microdomains of the sarcolemma, localize and enrich cardiac protective signaling molecules. Caveolin-3 (Cav-3), the dominant isoform in cardiac myocytes, is a determinant of caveolae formation. We hypothesized that cardiac myocyte-specific overexpression of Cav-3 would enhance the formation of caveolae and augment cardiac protection in vivo. Methods and Results Ischemic preconditioning (IPC) in vivo increased formation of caveolae. Adenovirus for Cav-3 increased caveolar formation and phosphorylation of survival kinases in cardiac myocytes. A transgenic (TG) mouse with cardiac myocyte-specific overexpression of Cav-3 (Cav-3 OE) showed enhanced formation of caveolae on the sarcolemma. Cav-3 OE mice subjected to ischemia/reperfusion injury had a significantly reduced infarct size relative to TGneg mice. Endogenous cardiac protection in Cav-3 OE mice was similar to wild-type mice undergoing IPC; no increased protection was observed in preconditioned Cav-3 OE mice. Cav-3 knockout mice did not show endogenous protection and showed no protection in response to IPC. Cav-3 OE mouse hearts had increased basal Akt and GSK3β phosphorylation comparable to wild-type mice exposed to IPC. Wortmannin, a PI3K inhibitor, attenuated basal phosphorylation of Akt and GSK3β and blocked cardiac protection in Cav-3 OE mice. Cav-3 OE mice had improved functional recovery and reduced apoptosis at 24 h of reperfusion. Conclusion Expression of caveolin-3 is both necessary and sufficient for cardiac protection, a conclusion that unites long-standing ultrastructural and molecular observations in the ischemic heart. The current results indicate that increased expression of caveolins, apparently via actions that depend on PI3K, has the potential to protect hearts exposed to ischemia-reperfusion injury. PMID:18936328

  9. Improving hospital efficiency: a process model of organizational change commitments.

    PubMed

    Nigam, Amit; Huising, Ruthanne; Golden, Brian R

    2014-02-01

    Improving hospital efficiency is a critical goal for managers and policy makers. We draw on participant observation of the perioperative coaching program in seven Ontario hospitals to develop knowledge of the process by which the content of change initiatives to increase hospital efficiency is defined. The coaching program was a change initiative involving the use of external facilitators with the goal of increasing perioperative efficiency. Focusing on the role of subjective understandings in shaping initiatives to improve efficiency, we show that physicians, nurses, administrators, and external facilitators all have differing frames of the problems that limit efficiency, and propose different changes that could enhance efficiency. Dynamics of strategic and contested framing ultimately shaped hospital change commitments. We build on work identifying factors that enhance the success of change efforts to improve hospital efficiency, highlighting the importance of subjective understandings and the politics of meaning-making in defining what hospitals change.

  10. Return of Viable Cardiac Function After Sonographic Cardiac Standstill in Pediatric Cardiac Arrest.

    PubMed

    Steffen, Katherine; Thompson, W Reid; Pustavoitau, Aliaksei; Su, Erik

    2017-01-01

    Sonographic cardiac standstill during adult cardiac arrest is associated with failure to get return to spontaneous circulation. This report documents 3 children whose cardiac function returned after standstill with extracorporeal membranous oxygenation. Sonographic cardiac standstill may not predict cardiac death in children.

  11. Beyond Enhancement: The Kennedy Center's Commitment to Education.

    ERIC Educational Resources Information Center

    Gordon, Derek E.; Stoner, Scott D.

    1995-01-01

    Asserts that exposure to high-quality arts performances with accompanying educational experiences enlivens teaching and learning. Maintains that few schools have taken advantage of opportunities provided by arts-presenting institutions. Describes resources from the John F. Kennedy Center for the Performing Arts. (CFR)

  12. Relationships between in-role performance and individual values, commitment, and organizational citizenship behavior among Israeli teachers.

    PubMed

    Cohen, Aaron; Liu, Ying

    2011-08-01

    This study examines the relationship between (1) individual values, (2) organizational and occupational commitment, and (3) organizational citizenship behavior (OCB) and in-role performance in a sample of 192 teachers employed in 10 secular Jewish schools (response rate of 64%). The results showed that individual values were related to all commitment forms examined here, but contrary to expectations, there was no clear distinction between values that represent conservation and self-transcendence and values that represent openness to change and self-enhancement in terms of their relationship either to commitment or to behavioral outcomes. Likewise, there was no clear distinction between the three dimensions of commitment (affective, continuance, and normative) or two commitment foci (organizational and occupational) in terms of their relationships to different values. Unsurprisingly, the findings showed a strong effect of commitment on OCB and in-role performance. The findings show that both individual values and commitment are concepts that can increase our understanding of employees' behavior in the workplace. We conclude by emphasizing the need for further research on the relationship between values, commitment, and performance and by suggesting some directions for such research.

  13. Effect of Enhanced External Counterpulsation and Cardiac Rehabilitation on Quality of Life, Plasma Nitric Oxide, Endothelin 1 and High Sensitive CRP in Patients With Coronary Artery Disease: A Pilot Study

    PubMed Central

    Shakouri, Seyed Kazem; Razavi, Zeynab; Eslamian, Fariba; Sadeghi-Bazargani, Homayoun; Ghaffari, Samad

    2015-01-01

    Objective To investigate the effect of enhanced external counterpulsation (EECP) on plasma nitric oxide (NO), Endothelin 1 (ET1), high sensitive C-reactive protein (HSCRP) and quality of life (QoL) in patients with coronary artery disease (CAD). Methods We conducted a pilot randomized clinical trial in order to evaluate plasma NO, ET1, HSCRP and QoL before and after twenty sessions of EECP (group A) and cardiac rehabilitation (CR, group B) in 42 patients with CAD (21 in each group). Results Forty-two patients (33 male and 9 female) were included in the study. The mean age was 58.2±10 years. The mean HSCRP was 1.52±0.7 in the EECP group and it was reduced to 1.27±0.4 after intervention. The reduction in HSCRP was not statistically significant in EECP and CR groups with p=0.33 and p=0.27, respectively. There was not significant improvement of NO, ET1, and QoL in the EECP and CR groups shortly after therapy (p>0.05). Conclusion Although the short-term EECP treatment in CAD patients improved HSCRP, NO, ET1, and QoL compared with the baseline those improvements are not statistically significant. Further studies are necessary with large study groups and more sessions. PMID:25932415

  14. Factors Predicting Faculty Commitment to the University.

    ERIC Educational Resources Information Center

    Fjortoft, Nancy

    This paper examines the effect of faculty rank, satisfaction with salary, working conditions, institutional reputation, perceived influence on institutional policies, participation in meetings, and perceived governance on organizational commitment (at both the departmental and institutional level) using a representative sample of 4,925 faculty.…

  15. Crime, Commitment and the Responsive Bystander.

    ERIC Educational Resources Information Center

    Moriarty, Thomas

    The paper describes a field experiment conducted at Jones Beach, New York, to determine (1) how responsive are individuals who witness a crime, and (2) under what conditions will bystanders take action to prevent a crime. The major independent variable in this study was the degree of prior commitment to the victim; whether or not the subject had…

  16. 24 CFR 203.7 - Commitment process.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES SINGLE... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Commitment process. 203.7 Section 203.7 Housing and Urban Development Regulations Relating to Housing and Urban Development...

  17. 24 CFR 203.7 - Commitment process.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES SINGLE... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Commitment process. 203.7 Section 203.7 Housing and Urban Development Regulations Relating to Housing and Urban Development...

  18. 24 CFR 203.7 - Commitment process.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES SINGLE... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 false Commitment process. 203.7 Section 203.7 Housing and Urban Development Regulations Relating to Housing and Urban Development...

  19. 24 CFR 203.7 - Commitment process.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES SINGLE... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Commitment process. 203.7 Section 203.7 Housing and Urban Development Regulations Relating to Housing and Urban Development...

  20. 24 CFR 203.7 - Commitment process.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES SINGLE... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Commitment process. 203.7 Section 203.7 Housing and Urban Development Regulations Relating to Housing and Urban Development...

  1. Work Commitment through the Life Cycle.

    ERIC Educational Resources Information Center

    Levitin, Teresa E.; Quinn, Robert P.

    Data obtained from a national, cross-sectional survey of the American work force were used to examine the relationship between age and an interview measure of psychological involvement with work (i.e., paid employment). For men, this relationship was curvilinear. Commitment began at a low level among the 16-20 year old men, rose to its highest…

  2. Organizational Commitment through Organizational Socialization Tactics

    ERIC Educational Resources Information Center

    Filstad, Cathrine

    2011-01-01

    Purpose: The aim of this paper is to investigate how organizational socialization tactics affect newcomers' organizational commitment and learning processes. Design/methodology/approach: A survey was conducted using a measurement tool based on Van Maanen and Schein's theory on organizational socialization tactics and Kuvaas' measurement tools of…

  3. Affective Commitment among Student Affairs Professionals

    ERIC Educational Resources Information Center

    Boehman, Joseph

    2007-01-01

    Student affairs professionals in the United States were surveyed to determine the predictive value of overall job satisfaction, organizational support, organizational politics, and work/nonwork interaction on affective organizational commitment. Results indicate that a supportive work environment leads to increased affective attachment to the…

  4. Resistance, Justice, and Commitment to Change

    ERIC Educational Resources Information Center

    Foster, Rex D.

    2010-01-01

    This research focused on individual responses to organizational change by exploring the relationships among individual resistance, organizational justice, and commitment to change following organizational change implementations in three organizations. To accomplish this, Web-based questionnaires were used to gather individual-level quantitative…

  5. Organizational Justice and Commitment in Interscholastic Sports

    ERIC Educational Resources Information Center

    Whisenant, Warren

    2005-01-01

    The purpose of this study was to determine the effect of three organizational justice dimensions on the commitment of high school student athletes (N = 480) to continue playing a referent sport. The athletes were asked to complete an instrument designed to assess their perceived levels of justice displayed by their coaches in three justice…

  6. Sex, Love, and the Committed Relationship

    ERIC Educational Resources Information Center

    Whitaker, Carl A.; And Others

    1976-01-01

    Six responses are presented to the question of relationship of love, sex, and commitment as revised by Sager in the Spring 1976 issue of this journal. Theoretical and historical perspectives as well as issues of coupling, eroticism, sexual dysfunction and therapy, and psychosexual development are discussed. (HLM)

  7. Committed to the Cause: James Forman Jr.

    ERIC Educational Resources Information Center

    Roach, Ronald

    2005-01-01

    Steeped in the values of the civil rights movement, James Forman Jr. has charted a path into academia that has demonstrated both a keen commitment to social justice as well as impressive legal and academic achievements. Among his most notable accomplishments prior to his Georgetown appointment in 2003, Forman co-founded the nationally acclaimed…

  8. Commitment at Work and Independence from Management.

    ERIC Educational Resources Information Center

    Belanger, Jacques; Edwards, Paul K.; Wright, Martyn

    2003-01-01

    Case study of a Canadian aluminum smelter through 15 interviews, observation, and employee survey (n=214) revealed high commitment, acceptance of change, and worker independence from management. This pattern emerged from a traditionally strong union presence. Comparison with other cases underlines the centrality of collective organization to…

  9. Public Television: Commitment to Children's Programs.

    ERIC Educational Resources Information Center

    Distance Education Report, 2000

    2000-01-01

    Illustrates public television's early commitment to children's programming, discussing the popularity of "Sesame Street" and noting other shows launched under Joan Ganz Cooney, president of CTW from 1970 until 1988. Discusses the erosion of television network ratings by cable television in the mid '80s, and concludes by posing questions…

  10. Organizational Commitment among Public Service Employees.

    ERIC Educational Resources Information Center

    Young, Brian S.; Worchel, Stephen; Woehr, David J.

    1998-01-01

    A study that examined factors associated with organizational commitment among 64 blue-collar workers found that the following were positively and significantly related: promotion satisfaction, job characteristics, communication, leadership satisfaction, job satisfaction, intrinsic and extrinsic exchange, and intrinsic and extrinsic rewards.…

  11. Influencing Organizational Commitment through Office Redesign

    ERIC Educational Resources Information Center

    Morrow, Paula C.; McElroy, James C.; Scheibe, Kevin P.

    2012-01-01

    Prior research on the effects of office redesign on work-related outcomes has been largely a theoretical and yielded mixed and conflicting findings. Expanding on individual reactions to office design changes as specified by social interference theory, we propose that office redesign affects organizational commitment and this relationship is…

  12. Supervising Trainees in Acceptance and Commitment Therapy for Treatment of Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Walser, Robyn D.; Westrup, Darrah

    2006-01-01

    Acceptance and Commitment Therapy (ACT, Hayes, Strosahl, & Wilson, 1999) is a behaviorally based intervention designed to target and reduce experiential avoidance and cognitive fusion (holding the thoughts in one's mind to be literally true) while at the same time helping clients to make powerful life enhancing behavioral changes that are in line…

  13. The Association of School Environment to Student Teachers' Satisfaction and Teaching Commitment

    ERIC Educational Resources Information Center

    Huang, Shwu-yong L.; Waxman, Hersh C.

    2009-01-01

    A supportive school environment is crucial to the enhancement of student teaching experiences. This study assesses student teachers' perceptions of secondary school environments, and then relates the perceptions to their satisfaction with school experiences and teaching commitment. The results show that considerable disparities between student…

  14. Cardiac Imaging System

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Although not available to all patients with narrowed arteries, balloon angioplasty has expanded dramatically since its introduction with an estimated further growth to 562,000 procedures in the U.S. alone by 1992. Growth has fueled demand for higher quality imaging systems that allow the cardiologist to be more accurate and increase the chances of a successful procedure. A major advance is the Digital Cardiac Imaging (DCI) System designed by Philips Medical Systems International, Best, The Netherlands and marketed in the U.S. by Philips Medical Systems North America Company. The key benefit is significantly improved real-time imaging and the ability to employ image enhancement techniques to bring out added details. Using a cordless control unit, the cardiologist can manipulate images to make immediate assessment, compare live x-ray and roadmap images by placing them side-by-side on monitor screens, or compare pre-procedure and post procedure conditions. The Philips DCI improves the cardiologist's precision by expanding the information available to him.

  15. Conceptual Commitments of AGI Systems: Editorial, Commentaries, and Response

    NASA Astrophysics Data System (ADS)

    2013-06-01

    Editorial: Conceptual Commitments of AGI Systems Haris Dindo / James Marshall / Giovanni Pezzulo 23 General Problems of Unified Theories of Cognition, and Another Conceptual Commitment of LIDA Benjamin Angerer / Stefan Schneider 26 LIDA, Committed to Consciousness Antonio Chella 28 The Radical Interactionism Conceptual Commitment Olivier L. Georgeon / David W. Aha 31 Commitments of the Soar Cognitive Architecture John E. Laird 36 Conceptual Commitments of AGI Projects Pei Wang 39 Will (dis)Embodied LIDA Agents be Socially Interactive? Travis J. Wiltshire / Emilio J. C. Lobato / Florian G. Jentsch / Stephen M. Fiore 42 Author's Response to Commentaries Steve Strain / Stan Franklin 48

  16. Cardiac Hegemony of Senescence

    PubMed Central

    Siddiqi, Sailay; Sussman, Mark A.

    2013-01-01

    Cardiac senescence and age-related disease development have gained general attention and recognition in the past decades due to increased accessibility and quality of health care. The advancement in global civilization is complementary to concerns regarding population aging and development of chronic degenerative diseases. Cardiac degeneration has been rigorously studied. The molecular mechanisms of cardiac senescence are on multiple cellular levels and hold a multilayer complexity level, thereby hampering development of unambiguous treatment protocols. In particular, the synergistic exchange of the senescence phenotype through a senescence secretome between myocytes and stem cells appears complicated and is of great future therapeutic value. The current review article will highlight hallmarks of senescence, cardiac myocyte and stem cell senescence, and the mutual exchange of senescent secretome. Future cardiac cell therapy approaches require a comprehensive understanding of myocardial senescence to improve therapeutic efficiency as well as efficacy. PMID:24349878

  17. Automatic classification of scar tissue in late gadolinium enhancement cardiac MRI for the assessment of left-atrial wall injury after radiofrequency ablation

    NASA Astrophysics Data System (ADS)

    Perry, Daniel; Morris, Alan; Burgon, Nathan; McGann, Christopher; MacLeod, Robert; Cates, Joshua

    2012-03-01

    Radiofrequency ablation is a promising procedure for treating atrial fibrillation (AF) that relies on accurate lesion delivery in the left atrial (LA) wall for success. Late Gadolinium Enhancement MRI (LGE MRI) at three months post-ablation has proven effective for noninvasive assessment of the location and extent of scar formation, which are important factors for predicting patient outcome and planning of redo ablation procedures. We have developed an algorithm for automatic classification in LGE MRI of scar tissue in the LA wall and have evaluated accuracy and consistency compared to manual scar classifications by expert observers. Our approach clusters voxels based on normalized intensity and was chosen through a systematic comparison of the performance of multivariate clustering on many combinations of image texture. Algorithm performance was determined by overlap with ground truth, using multiple overlap measures, and the accuracy of the estimation of the total amount of scar in the LA. Ground truth was determined using the STAPLE algorithm, which produces a probabilistic estimate of the true scar classification from multiple expert manual segmentations. Evaluation of the ground truth data set was based on both inter- and intra-observer agreement, with variation among expert classifiers indicating the difficulty of scar classification for a given a dataset. Our proposed automatic scar classification algorithm performs well for both scar localization and estimation of scar volume: for ground truth datasets considered easy, variability from the ground truth was low; for those considered difficult, variability from ground truth was on par with the variability across experts.

  18. Automatic classification of scar tissue in late gadolinium enhancement cardiac MRI for the assessment of left-atrial wall injury after radiofrequency ablation.

    PubMed

    Perry, Daniel; Morris, Alan; Burgon, Nathan; McGann, Christopher; Macleod, Robert; Cates, Joshua

    2012-02-23

    Radiofrequency ablation is a promising procedure for treating atrial fibrillation (AF) that relies on accurate lesion delivery in the left atrial (LA) wall for success. Late Gadolinium Enhancement MRI (LGE MRI) at three months post-ablation has proven effective for noninvasive assessment of the location and extent of scar formation, which are important factors for predicting patient outcome and planning of redo ablation procedures. We have developed an algorithm for automatic classification in LGE MRI of scar tissue in the LA wall and have evaluated accuracy and consistency compared to manual scar classifications by expert observers. Our approach clusters voxels based on normalized intensity and was chosen through a systematic comparison of the performance of multivariate clustering on many combinations of image texture. Algorithm performance was determined by overlap with ground truth, using multiple overlap measures, and the accuracy of the estimation of the total amount of scar in the LA. Ground truth was determined using the STAPLE algorithm, which produces a probabilistic estimate of the true scar classification from multiple expert manual segmentations. Evaluation of the ground truth data set was based on both inter- and intra-observer agreement, with variation among expert classifiers indicating the difficulty of scar classification for a given a dataset. Our proposed automatic scar classification algorithm performs well for both scar localization and estimation of scar volume: for ground truth datasets considered easy, variability from the ground truth was low; for those considered difficult, variability from ground truth was on par with the variability across experts.

  19. Improving knowledge of strategic goals and the impact on organizational commitment.

    PubMed

    Enriquez, V; McBride, J; Paxton, L

    2001-01-01

    A large health maintenance organization (HMO) in San Diego, California developed a year-long communication plan to increase employee knowledge of the company's strategic goals and enhance organizational commitment. Survey results indicated: Respondents remembered significantly more strategic goals after program implementation. Respondents who had personal involvement in achieving goals remembered significantly more goals than those without involvement. Department meetings and the employee/physician newsletter were identified as primary sources for learning about goals. These findings suggest that organizations may be able to strengthen employee commitment by increasing awareness of the organization's strategic goals and encouraging employees to become personally involved in the achievement of those goals.

  20. Schizophrenia--time to commit to policy change.

    PubMed

    Fleischhacker, W Wolfgang; Arango, Celso; Arteel, Paul; Barnes, Thomas R E; Carpenter, William; Duckworth, Ken; Galderisi, Silvana; Halpern, Lisa; Knapp, Martin; Marder, Stephen R; Moller, Mary; Sartorius, Norman; Woodruff, Peter

    2014-04-01

    Care and outcomes for people with schizophrenia have improved in recent years, but further progress is needed to help more individuals achieve an independent and fulfilled life. This report sets out the current need, informs policy makers and all relevant stakeholders who influence care quality, and supports their commitment to creating a better future. The authors recommend the following policy actions, based on research evidence, stakeholder consultation, and examples of best practice worldwide. (1) Provide an evidence-based, integrated care package for people with schizophrenia that addresses their mental and physical health needs. (2) Provide support for people with schizophrenia to enter and to remain in their community, and develop mechanisms to help guide them through the complex benefit and employment systems. (3) Provide concrete support, information, and educational programs to families and carers on how to enhance care for an individual living with schizophrenia in a manner that entails minimal disruption to their lives. (4) All stakeholders, including organizations that support people living with schizophrenia, should be consulted to regularly revise, update, and improve policy on the management of schizophrenia. (5) Provide support, which is proportionate to the impact of the disease, for research and development of new treatments. (6) Establish adequately funded, ongoing, and regular awareness-raising campaigns that form an integral part of routine plans of action. Implementation of the above recommendations will require engagement by every stakeholder, but with commitment from all, change can be achieved.

  1. Schizophrenia—Time to Commit to Policy Change

    PubMed Central

    Fleischhacker, W. Wolfgang

    2014-01-01

    Care and outcomes for people with schizophrenia have improved in recent years, but further progress is needed to help more individuals achieve an independent and fulfilled life. This report sets out the current need, informs policy makers and all relevant stakeholders who influence care quality, and supports their commitment to creating a better future. The authors recommend the following policy actions, based on research evidence, stakeholder consultation, and examples of best practice worldwide. (1) Provide an evidence-based, integrated care package for people with schizophrenia that addresses their mental and physical health needs. (2) Provide support for people with schizophrenia to enter and to remain in their community, and develop mechanisms to help guide them through the complex benefit and employment systems. (3) Provide concrete support, information, and educational programs to families and carers on how to enhance care for an individual living with schizophrenia in a manner that entails minimal disruption to their lives. (4) All stakeholders, including organizations that support people living with schizophrenia, should be consulted to regularly revise, update, and improve policy on the management of schizophrenia. (5) Provide support, which is proportionate to the impact of the disease, for research and development of new treatments. (6) Establish adequately funded, ongoing, and regular awareness-raising campaigns that form an integral part of routine plans of action. Implementation of the above recommendations will require engagement by every stakeholder, but with commitment from all, change can be achieved. PMID:24778411

  2. Commitments to future retreat of Antarctic and Greenland ice sheets

    NASA Astrophysics Data System (ADS)

    DeConto, Robert; Pollard, David

    2016-04-01

    The agreement reached at the COP21 United Nations Conference on Climate Change is aimed at limiting future increases in global mean temperature below 2°C. Here, we use a continental ice sheet/shelf model with new treatments of meltwater-enhanced calving (hydrofracturing) and marine terminating ice-cliffs, to explore future commitments to sea-level rise given limits of global mean warming between 1 and 3°C. In this case, ice-sheet model physics are calibrated against past ice-sheet response to temperatures warmer than today. The ice-sheet model is coupled to highly resolved atmosphere and ocean-model components, with imposed limits on future warming designed to mimic the idealized limits discussed at COP21. Both the short and long-term potential rise in global mean sea level are discussed in light of the range of allowances agreed in Paris. We also explore the sensitivity of Greenland and Antarctic ice sheets to plausible ranges of atmospheric versus ocean warming consistent with global mean temperatures between 1 and 3°C; and the resulting long-term commitments to sea-level rise over the coming centuries and millennia.

  3. Security-constrained unit commitment with flexible operating modes

    NASA Astrophysics Data System (ADS)

    Lu, Bo

    The electricity industry throughout the world, which has long been dominated by vertically integrated utilities, is facing enormous challenges. To enhance the competition in electricity industry, vertically integrated utilities are evolving into a distributed and competitive industry in which market forces drive the price of electricity and possibly reduce the net cost of supplying electrical loads through increased competition. To excel in the competition, generation companies (GENCOs) will acquire additional generating units with flexible operating capability which allows a timely response to the continuous changes in power system conditions. This dissertation considers the short-term scheduling of generating units with flexible modes of operation in security-constrained unit commitment (SCUC). Among the units considered in this study are combined cycle units, fuel switching/blending units, photovoltaic/battery system, pumped-storage units, and cascaded hydro units. The proposed security-constrained unit commitment solution will include a detailed model of transmission system which could impact the short-term scheduling of units with flexible operation modes.

  4. Preferences, constraints or schemas of devotion? Exploring Norwegian mothers' withdrawals from high-commitment careers.

    PubMed

    Halrynjo, Sigtona; Lyng, Selma Therese

    2009-06-01

    Despite decades of focus on gender equality and work-family balance, parenthood still affects mothers' and fathers' careers differently. Drawing on in-depth interviews with Norwegian mothers who are relinquishing high-commitment careers of law and consultancy, this paper questions the adequacy of established explanations emphasizing constraints vs. individual preferences. Our sample of female professionals living in a well-developed welfare state is particularly apt to explore the processes and mechanisms upholding the statistically gendered pattern of women reducing their work commitment after childbirth. These doubly privileged mothers might be considered to have the best odds for combining career and work commitment with motherhood. Thus, we argue that the approach emphasizing practical constraints does not sufficiently account for the withdrawal from high-commitment careers among these female professionals. Nevertheless, we are not content with the claim of Preference Theory that this shift in commitment is merely a matter of 'not-so-dedicated' women discovering their 'genuine' preferences. Rather, in order to understand why and how this shift occurs, we explore the culturally constructed rationalities and schemas of both work and family devotions. We specifically examine the circumstances, mechanisms and steps in a seemingly individual process of making the shift in commitment from a promising career to a family-friendly job. Moreover, the analysis demonstrates how generous parental leave arrangements designed to enhance gender equality and work-family balance by simply reducing practical constraints may have limited--or even counterproductive--impact within high-commitment occupations where the 'irreplaceability' of workers is taken for granted. Our findings indicate that unless the culturally (re)produced discourses, demands and expectations of both work and family are exposed and challenged, even intentionally gender neutral work-family policies will

  5. Cardiac tumors: echo assessment.

    PubMed

    Mankad, Rekha; Herrmann, Joerg

    2016-12-01

    Cardiac tumors are exceedingly rare (0.001-0.03% in most autopsy series). They can be present anywhere within the heart and can be attached to any surface or be embedded in the myocardium or pericardial space. Signs and symptoms are nonspecific and highly variable related to the localization, size and composition of the cardiac mass. Echocardiography, typically performed for another indication, may be the first imaging modality alerting the clinician to the presence of a cardiac mass. Although echocardiography cannot give the histopathology, certain imaging features and adjunctive tools such as contrast imaging may aid in the differential diagnosis as do the adjunctive clinical data and the following principles: (1) thrombus or vegetations are the most likely etiology, (2) cardiac tumors are mostly secondary and (3) primary cardiac tumors are mostly benign. Although the finding of a cardiac mass on echocardiography may generate confusion, a stepwise approach may serve well practically. Herein, we will review such an approach and the role of echocardiography in the assessment of cardiac masses.

  6. Cardiac tumors: echo assessment

    PubMed Central

    Mankad, Rekha

    2016-01-01

    Cardiac tumors are exceedingly rare (0.001–0.03% in most autopsy series). They can be present anywhere within the heart and can be attached to any surface or be embedded in the myocardium or pericardial space. Signs and symptoms are nonspecific and highly variable related to the localization, size and composition of the cardiac mass. Echocardiography, typically performed for another indication, may be the first imaging modality alerting the clinician to the presence of a cardiac mass. Although echocardiography cannot give the histopathology, certain imaging features and adjunctive tools such as contrast imaging may aid in the differential diagnosis as do the adjunctive clinical data and the following principles: (1) thrombus or vegetations are the most likely etiology, (2) cardiac tumors are mostly secondary and (3) primary cardiac tumors are mostly benign. Although the finding of a cardiac mass on echocardiography may generate confusion, a stepwise approach may serve well practically. Herein, we will review such an approach and the role of echocardiography in the assessment of cardiac masses. PMID:27600455

  7. [Involuntary commitment: implication for psychiatric nursing practice].

    PubMed

    Moreira, Lilian Hortale de Oliveira; Loyola, Cristina Maria Douat

    2011-06-01

    The characteristics of involuntary psychiatric commitment (IPI) may cause implications on the nursing/patient relationship. The objectives of this study were to list the forms of nursing care delivered to psychiatric patients, according to the type of commitment; analyze the reaction of the nursing team towards the IPI patient, and discuss on the implications that IPI have on the practice o psychiatric nursing. A field research was performed with the nursing team of a psychiatric institution in Rio de Janeiro. After 50 hours of participant observation and 9 of focal group meetings, we found that the teams are concerned with the clinical evolution of the patients. No references of the nursing team to the IPI patient were observed. There are no records or actions of any kind that would suggest a specific look towards this type of patient. Nursing professionals are not able to clearly identify this type of patient, thus the care is provided as per the patient's needs or requests.

  8. Commentary: civil commitment and its reform.

    PubMed

    Simpson, Alexander I F

    2015-03-01

    Internationally, civil commitment laws have gone through substantial reforms in the past 50 years. Discernible shifts from the medically paternalistic to the excessively legalistic may be giving way to a blending of legislative intent under the rubric of therapeutic jurisprudence. In the light of those international movements, Shao and Xie describe how China's new mental health law shows the impact of these international and local influences on the development and practice of mental health law in China. The new Law was passed in 2012. It sets a broad vision for mental health services and mental health promotion in Chinese society as well as providing the legal framework for civil commitment. Practicalities of implementation may be highly significant in the success of the legislation.

  9. Safe Commits for Transactional Featherweight Java

    NASA Astrophysics Data System (ADS)

    Thuong Tran, Thi Mai; Steffen, Martin

    Transactions are a high-level alternative for low-level concurrency-control mechanisms such as locks, semaphores, monitors. A recent proposal for integrating transactional features into programming languages is Transactional Featherweight Java (TFJ), extending Featherweight Java by adding transactions. With support for nested and multi-threaded transactions, its transactional model is rather expressive. In particular, the constructs governing transactions - to start and to commit a transaction - can be used freely with a non-lexical scope. On the downside, this flexibility also allows for an incorrect use of these constructs, e.g., trying to perform a commit outside any transaction. To catch those kinds of errors, we introduce a static type and effect system for the safe use of transactions for TFJ. We prove the soundness of our type system by subject reduction.

  10. Teaching in a web of commitments.

    PubMed

    Sutphen, Molly; Solbrekke, Tone Dyrdal

    2012-04-01

    Drawing on interviews and survey results from a national study of nursing education, this article discusses teaching professional responsibilities in prelicensure nursing education and explores how to help students reflect on multiple commitments they will meet in nursing. Inspired by the moral philosopher Larry May's communitarian approach, we suggest strategies for teaching students a broad notion of professional responsibility, including the profession's moral and societal responsibilities.

  11. [Cardiac manifestations of mitochondrial diseases].

    PubMed

    Ritzenthaler, Thomas; Luis, David; Hullin, Thomas; Fayssoil, Abdallah

    2015-05-01

    Mitochondrial diseases are multi-system disorders in relation with mitochondrial DNA and/or nuclear DNA abnormalities. Clinical pictures are heterogeneous, involving endocrine, cardiac, neurologic or sensory systems. Cardiac involvements are morphological and electrical disturbances. Prognosis is worsened in case of cardiac impairment. Treatments are related to the type of cardiac dysfunction including medication or pacemaker implantation.

  12. Climate commitment in an uncertain world

    NASA Astrophysics Data System (ADS)

    Armour, K. C.; Roe, G. H.

    2011-01-01

    Climate commitment—the warming that would still occur given no further human influence—is a fundamental metric for both science and policy. It informs us of the minimum climate change we face and, moreover, depends only on our knowledge of the natural climate system. Studies of the climate commitment due to CO2 find that global temperature would remain near current levels, or even decrease slightly, in the millennium following the cessation of emissions. However, this result overlooks the important role of the non-CO2 greenhouse gases and aerosols. This paper shows that global energetics require an immediate and significant warming following the cessation of emissions as aerosols are quickly washed from the atmosphere, and the large uncertainty in current aerosol radiative forcing implies a large uncertainty in the climate commitment. Fundamental constraints preclude Earth returning to pre-industrial temperatures for the indefinite future. These same constraints mean that observations are currently unable to eliminate the possibility that we are already beyond the point where the ultimate warming will exceed dangerous levels. Models produce a narrower range of climate commitment, but undersample observed forcing constraints.

  13. Constructing rich false memories of committing crime.

    PubMed

    Shaw, Julia; Porter, Stephen

    2015-03-01

    Memory researchers long have speculated that certain tactics may lead people to recall crimes that never occurred, and thus could potentially lead to false confessions. This is the first study to provide evidence suggesting that full episodic false memories of committing crime can be generated in a controlled experimental setting. With suggestive memory-retrieval techniques, participants were induced to generate criminal and noncriminal emotional false memories, and we compared these false memories with true memories of emotional events. After three interviews, 70% of participants were classified as having false memories of committing a crime (theft, assault, or assault with a weapon) that led to police contact in early adolescence and volunteered a detailed false account. These reported false memories of crime were similar to false memories of noncriminal events and to true memory accounts, having the same kinds of complex descriptive and multisensory components. It appears that in the context of a highly suggestive interview, people can quite readily generate rich false memories of committing crime.

  14. Appliance Commitment for Household Load Scheduling

    SciTech Connect

    Du, Pengwei; Lu, Ning

    2011-06-30

    This paper presents a novel appliance commitment algorithm that schedules thermostatically-controlled household loads based on price and consumption forecasts considering users comfort settings to meet an optimization objective such as minimum payment or maximum comfort. The formulation of an appliance commitment problem was described in the paper using an electrical water heater load as an example. The thermal dynamics of heating and coasting of the water heater load was modeled by physical models; random hot water consumption was modeled with statistical methods. The models were used to predict the appliance operation over the scheduling time horizon. User comfort was transformed to a set of linear constraints. Then, a novel linear, sequential, optimization process was used to solve the appliance commitment problem. The simulation results demonstrate that the algorithm is fast, robust, and flexible. The algorithm can be used in home/building energy-management systems to help household owners or building managers to automatically create optimal load operation schedules based on different cost and comfort settings and compare cost/benefits among schedules.

  15. Advantages of a leveled commitment contracting protocol

    SciTech Connect

    Sandholm, T.W.; Lesser, V.R.

    1996-12-31

    In automated negotiation systems consisting of self-interested agents, contracts have traditionally been binding. Such contracts do not allow agents to efficiently accommodate future events. Game theory has proposed contingency contracts to solve this problem. Among computational agents, contingency contracts are often impractical due to large numbers of interdependent and unanticipated future events to be conditioned on, and because some events are not mutually observable. This paper proposes a leveled commitment contracting protocol that allows self-interested agents to efficiently accommodate future events by having the possibility of unilaterally decommitting from a contract based on local reasoning. A decommitment penalty is assigned to both agents in a contract: to be freed from the contract, an agent only pays this penalty to the other party. It is shown through formal analysis of several contracting settings that this leveled commitment feature in a contracting protocol increases Pareto efficiency of deals and can make contracts individually rational when no full commitment contract can. This advantage holds even if the agents decommit manipulatively.

  16. Impact of committed individuals on vaccination behavior

    NASA Astrophysics Data System (ADS)

    Liu, Xiao-Tao; Wu, Zhi-Xi; Zhang, Lianzhong

    2012-11-01

    We study how the presence of committed vaccinators, a small fraction of individuals who consistently hold the vaccinating strategy and are immune to influence, impact the vaccination dynamics in well-mixed and spatially structured populations. For this purpose, we develop an epidemiological game-theoretic model of a flu-like vaccination by integrating an epidemiological process into a simple agent-based model of adaptive learning, where individuals (except for those committed ones) use anecdotal evidence to estimate costs and benefits of vaccination. We show that the committed vaccinators, acting as “steadfast role models” in the populations, can efficiently avoid the clustering of susceptible individuals and stimulate other imitators to take vaccination, hence contributing to the promotion of vaccine uptake. We substantiate our findings by making comparative studies of our model on a full lattice and on a randomly diluted one. Our work is expected to provide valuable information for decision-making and design more effective disease-control strategy.

  17. Job Stress and Organizational Commitment among Mentoring Coordinators

    ERIC Educational Resources Information Center

    Michael, Orly; Court, Deborah; Petal, Pnina

    2009-01-01

    Purpose: This research aims to examine the impact of job stress on the organizational commitment of a random, representative sample of coordinators in the Israeli educational mentoring organization PMP. Organizational commitment, including affective, continuance and normative commitment, refers to worker relations in the organization, and how…

  18. 48 CFR 2401.602-3 - Ratification of unauthorized commitments.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the corrective management measures to prevent future unauthorized commitments. If the individual who... unauthorized commitments. 2401.602-3 Section 2401.602-3 Federal Acquisition Regulations System DEPARTMENT OF..., Contracting Authority, and Responsibilities 2401.602-3 Ratification of unauthorized commitments....

  19. Predicting Organizational Commitment from Organizational Culture in Turkish Primary Schools

    ERIC Educational Resources Information Center

    Ipek, Cemalettin

    2010-01-01

    This study aims to describe organizational culture and commitment and to predict organizational commitment from organizational culture in Turkish primary schools. Organizational Culture Scale (Ipek "1999") and Organizational Commitment Scale (Balay "2000") were used in the data gathering process. The data were collected from…

  20. The Relationship between Employee Commitment and Conflict Resolution Behavior

    ERIC Educational Resources Information Center

    London, Manuel; Howat, Gary

    1978-01-01

    This study examined the relationships between the use of five conflict resolution strategies (withdrawing, smoothing, compromising, forcing, and confronting) and three measures of employee commitment (commitment to the organization, profession, and community). The relationships varied between the different types of commitment and between…

  1. Personal, Role, Structural, Alternative and Affective Correlates of Organizational Commitment.

    DTIC Science & Technology

    1982-01-01

    Commitment Among Chinese Workers Employee commitment to organizations has been the topic of considerable conceptual and empirical attention in recent years...Steers, R.M., Mowday, R.T., & Porter, L.W., Employee Commitment to organizations: A conceptual review. ONR Technical Report 7, Graduate School of

  2. Effects of Team and Organizational Commitment--A Longitudinal Study

    ERIC Educational Resources Information Center

    Neininger, Alexandra; Lehmann-Willenbrock, Nale; Kauffeld, Simone; Henschel, Angela

    2010-01-01

    Retention management, i.e., keeping qualified employees, is a top priority for contemporary organizations. Commitment, and especially team commitment, can be the key to mastering this challenge. There is a lack of longitudinal research concerning the development and the direction of the effects of team commitment over time. In a longitudinal…

  3. 12 CFR 1807.501 - Commitment for use.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Commitment for use. 1807.501 Section 1807.501 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY CAPITAL MAGNET FUND Leveraging and Commitment Requirement § 1807.501 Commitment for use. (a) CMF awards shall...

  4. 12 CFR 1807.501 - Commitment for use.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Commitment for use. 1807.501 Section 1807.501 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY CAPITAL MAGNET FUND Leveraging and Commitment Requirement § 1807.501 Commitment for use. (a) CMF awards shall...

  5. 12 CFR 1807.501 - Commitment for use.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 9 2013-01-01 2013-01-01 false Commitment for use. 1807.501 Section 1807.501 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY CAPITAL MAGNET FUND Leveraging and Commitment Requirement § 1807.501 Commitment for use. (a) CMF awards shall...

  6. 12 CFR 1807.501 - Commitment for use.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 9 2012-01-01 2012-01-01 false Commitment for use. 1807.501 Section 1807.501 Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY CAPITAL MAGNET FUND Leveraging and Commitment Requirement § 1807.501 Commitment for use. (a) CMF awards shall...

  7. Satisfied and Dissatisfied Commitment: Teachers in Three Generations

    ERIC Educational Resources Information Center

    Choi, Pik Lin; Tang, Sylvia Yee Fan

    2011-01-01

    This paper explores the self-appraisal of teacher commitment and their associated emotional experiences in the first ten years of teaching among three generations of Hong Kong teachers. Findings affirm previous view that high commitment level of teachers is characterized with psychological attachment to the commitment objects. However the…

  8. Professional Commitment: An Analysis of Students and Alumni.

    ERIC Educational Resources Information Center

    Fjortoft, Nancy F.; Lee, Mary W. L.

    "Professional commitment" has been defined as "one's attitude toward one's profession or vocation." This study developed and tested a model to predict the development of professional commitment in students by examining the qualities of the college experience that may lead to that commitment. Factors such as background and…

  9. Role of Cardiac MR Imaging in Cardiomyopathies.

    PubMed

    Kramer, Christopher M

    2015-06-01

    Cardiac MR imaging has made major inroads in the new millennium in the diagnosis and assessment of prognosis for patients with cardiomyopathies. Imaging of left and right ventricular structure and function and tissue characterization with late gadolinium enhancement (LGE) as well as T1 and T2 mapping enable accurate diagnosis of the underlying etiology. In the setting of coronary artery disease, either transmurality of LGE or contractile reserve in response to dobutamine can assess the likelihood of recovery of function after revascularization. The presence of scar reduces the likelihood of a response to medical therapy and to cardiac resynchronization therapy in heart failure. The presence and extent of LGE relate to overall cardiovascular outcome in cardiomyopathies. A major role for cardiac MR imaging in cardiomyopathies is to identify myocardial scar for diagnostic and prognostic purposes.

  10. Cardiac Catheterization (For Kids)

    MedlinePlus

    ... done during a cardiac catheterization include: closing small holes inside the heart repairing leaky or narrow heart ... bandage. It's normal for the site to be black and blue, red, or slightly swollen for a ...

  11. Cardiac Catheterization (For Teens)

    MedlinePlus

    ... a person will have only a small puncture hole where the catheter was put in. Doctors usually ... done using a cardiac catheterization, including: closing small holes inside the heart repairing leaky or narrow heart ...

  12. Cardiac glycoside overdose

    MedlinePlus

    ... found in the leaves of the digitalis (foxglove) plant. This plant is the original source of this medicine. People ... Digitoxin (Crystodigin) Digoxin (Lanoxicaps, Lanoxin) Besides the foxglove plant, cardiac glycosides also occur naturally in plants such ...

  13. Commitment in different relationships statuses: validation study of the personal commitment scale.

    PubMed

    Monteiro, Ana Pego; Costa-Ramalho, Susana; Ribeiro, Maria Teresa; Pinto, Alexandra Marques

    2015-06-03

    This study presents the validation process of the Portuguese version of the short-form Dedication Scale (Rhoades, Stanley, & Markman, 2006; Stanley, 1986), with a sample of 924 participants in different relationship statutes. With 14 items, this short version is recommended by the authors for its simple use, when wanting to measure commitment in romantic relationships. Confirmatory factor analysis showed that the instrument did not have a totally acceptable fit with the data so an exploratory factor analysis was conducted. This revealed a one-dimensional structure of the scale, and led to the exclusion of two items, which relate to a distinct meta-commitment dimension. In sum, the Portuguese version (ECP - Personal Commitment Scale) has 12 items, with good internal consistency (α = .82), correlations item-total between .36 and .60, and good criteria validity (p < .001). Its use for research is therefore appropriate. In a second study, significant differences were found between the participants' four relationship statuses (dating non-cohabiting and cohabiting relationships, formal unions and marriage) (p < .001; η2 p = .03). Results showed that married participants were more committed than those in a formal union, even when controlling for several relational and socio-demographic variables. No differences were found between cohabiting and non-cohabiting dating participants. Men reported higher levels of commitment than women (p < .001; η2 p = .02). Implications and suggestions for future research are discussed.

  14. Cardiac imaging in adults

    SciTech Connect

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  15. 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

    ... economy of the United States constituted by the grave acts of terrorism and threats of terrorism committed... United States nationals or the United States. The actions of persons who commit, threaten to commit, or... policy, and economy of the United States. For this reason, the national emergency declared in...

  16. [Intrinsic cardiac ganglia].

    PubMed

    Birand, Ahmet

    2008-12-01

    Heart has been considered as the source and the seat of emotions, passion and love. But from the dawn of XIXth century, scientists have emphasized that the heart, though life depends on its ceaseless activity, is merely a electromechanical pump, pumping oxygenated blood. Nowadays, we all know that heart pumps blood commensurate with the needs of the body and this unending toil, and its regulation depends on the intrinsic properties of the myocardium, Frank-Starling Law and neurohumoral contribution. It has been understood, though not clearly enough, that these time-tensions may cause structural or functional cardiac impairments and arrhythmias are related to the autonomic nervous system. Less well known and less taken in account in daily cardiology practice is the fact that heart has an intrinsic cardiac nervous system, or "heart brain" consisting of complex ganglia, intrinsic cardiac ganglia containing afferent (receiving), local circuit (interneurons) and efferent (transmitting) sympathetic and parasympathetic neurons. This review enlightens structural and functional aspects of intrinsic cardiac ganglia as the very first step in the regulation of cardiac function. This issue is important for targets of pharmacological treatment and techniques of cardiac surgery interventions as repair of septal defects, valvular interventions and congenital corrections.

  17. Cardiac septic pulmonary embolism

    PubMed Central

    Song, Xin yu; Li, Shan; Cao, Jian; Xu, Kai; Huang, Hui; Xu, Zuo jun

    2016-01-01

    Abstract Based on the source of the embolus, septic pulmonary embolism (SPE) can be classified as cardiac, peripheral endogenous, or exogenous. Cardiac SPEs are the most common. We conducted a retrospective analysis of 20 patients with cardiac SPE hospitalized between 1991 and 2013 at a Chinese tertiary referral hospital. The study included 14 males and 6 females with a median age of 38.1 years. Fever (100%), cough (95%), hemoptysis (80%), pleuritic chest pain (80%), heart murmur (80%), and moist rales (75%) were common clinical manifestations. Most patients had a predisposing condition: congenital heart disease (8 patients) and an immunocompromised state (5 patients) were the most common. Staphylococcal (8 patients) and Streptococcal species (4 patients) were the most common causative pathogens. Parenchymal opacities, nodules, cavitations, and pleural effusions were the most common manifestations observed via computed tomography (CT). All patients exhibited significant abnormalities by echocardiography, including 15 patients with right-sided vegetations and 4 with double-sided vegetations. All patients received parenteral antimicrobial therapy as an initial treatment. Fourteen patients received cardiac surgery, and all survived. Among the 6 patients who did not undergo surgery, only 1 survived. Most patients in our cardiac SPE cohort had predisposing conditions. Although most exhibited typical clinical manifestations and radiography, they were nonspecific. For suspected cases of SPE, blood culture, echocardiography, and CT pulmonary angiography (CTPA) are important measures to confirm an early diagnosis. Vigorous early therapy, including appropriate antibiotic treatment and timely cardiac surgery to eradicate the infective source, is critical. PMID:27336870

  18. Quantum bit commitment with cheat sensitive binding and approximate sealing

    NASA Astrophysics Data System (ADS)

    Li, Yan-Bing; Xu, Sheng-Wei; Huang, Wei; Wan, Zong-Jie

    2015-04-01

    This paper proposes a cheat-sensitive quantum bit commitment scheme based on single photons, in which Alice commits a bit to Bob. Here, Bob’s probability of success at cheating as obtains the committed bit before the opening phase becomes close to \\frac{1}{2} (just like performing a guess) as the number of single photons used is increased. And if Alice alters her committed bit after the commitment phase, her cheating will be detected with a probability that becomes close to 1 as the number of single photons used is increased. The scheme is easy to realize with present day technology.

  19. Commitment: Functions, Formation, and the Securing of Romantic Attachment.

    PubMed

    Stanley, Scott M; Rhoades, Galena K; Whitton, Sarah W

    2010-12-01

    In this theoretical paper, we review central concepts in the psychological literature on relationship commitment to provide a foundation to discuss two themes related to long-term romantic relationships and marriages. First, we describe and discuss the role that commitment plays in stabilizing romantic attachment. Second, we use empirical research on cohabitation to highlight how the formation of commitment can be undermined by what are now common trajectories of couple development. The first topic underscores an increasingly important role for commitment in an age of companionate marriage. The second topic draws attention to dynamics that can affect the strength of romantic commitments, especially in marriage.

  20. Deletion of FoxO1 leads to shortening of QRS by increasing Na(+) channel activity through enhanced expression of both cardiac NaV1.5 and β3 subunit.

    PubMed

    Cai, Benzhi; Wang, Ning; Mao, Weike; You, Tao; Lu, Yan; Li, Xiang; Ye, Bo; Li, Faqian; Xu, Haodong

    2014-09-01

    Our in vitro studies revealed that a transcription factor, Forkhead box protein O1 (FoxO1), negatively regulates the expression of NaV1.5, a main α subunit of the cardiac Na(+) channel, by altering the promoter activity of SCN5a in HL-1 cardiomyocytes. The in vivo role of FoxO1 in the regulation of cardiac NaV1.5 expression remains unknown. The present study aimed to define the role of FoxO1 in the regulation of NaV1.5 expression and cardiac Na(+) channel activity in mouse ventricular cardiomyocytes and assess the cardiac electrophysiological phenotype of mice with cardiac FoxO1 deletion. Tamoxifen-induced and cardiac-specific FoxO1 deletion was confirmed by polymerase chain reaction (PCR). Cardiac FoxO1 deletion failed to result in either cardiac functional changes or hypertrophy as assessed by echocardiography and individual ventricular cell capacitances, respectively. Western blotting showed that FoxO1 was significantly decreased while NaV1.5 protein level was significantly increased in mouse hearts with FoxO1 deletion. Reverse transcription-PCR (RT-PCR) revealed that FoxO1 deletion led to an increase in NaV1.5 and Na(+) channel subunit β3 mRNA, but not β1, 2, and 4, or connexin 43. Whole patch-clamp recordings demonstrated that cardiac Na(+) currents were significantly augmented by FoxO1 deletion without affecting the steady-state activation and inactivation, leading to accelerated depolarization of action potentials in mouse ventricular cardiomyocytes. Electrocardiogram recordings showed that the QRS complex was significantly shortened and the P wave amplitude was significantly increased in conscious and unrestrained mice with cardiac FoxO1 deletion. NaV1.5 expression was decreased in the peri-infarct (border-zone) of mice with myocardial infarction and FoxO1 accumulated in the cardiomyocyte nuclei of chronic ischemic human hearts. Our findings indicate that FoxO1 plays an important role in the regulation of NaV1.5 and β3 subunit expressions as well as Na

  1. Enabling microscale and nanoscale approaches for bioengineered cardiac tissue.

    PubMed

    Chan, Vincent; Raman, Ritu; Cvetkovic, Caroline; Bashir, Rashid

    2013-03-26

    In this issue of ACS Nano, Shin et al. present their finding that the addition of carbon nanotubes (CNT) in gelatin methacrylate (GelMA) results in improved functionality of bioengineered cardiac tissue. These CNT-GelMA hybrid materials demonstrate cardiac tissue with enhanced electrophysiological performance; improved mechanical integrity; better cell adhesion, viability, uniformity, and organization; increased beating rate and lowered excitation threshold; and protective effects against cardio-inhibitory and cardio-toxic drugs. In this Perspective, we outline recent progress in cardiac tissue engineering and prospects for future development. Bioengineered cardiac tissues can be used to build "heart-on-a-chip" devices for drug safety and efficacy testing, fabricate bioactuators for biointegrated robotics and reverse-engineered life forms, treat abnormal cardiac rhythms, and perhaps one day cure heart disease with tissue and organ transplants.

  2. Matrix identity and tractional forces influence indirect cardiac reprogramming

    PubMed Central

    Kong, Yen P.; Carrion, Bita; Singh, Rahul K.; Putnam, Andrew J.

    2013-01-01

    Heart regeneration through in vivo cardiac reprogramming has been demonstrated as a possible regenerative strategy. While it has been reported that cardiac reprogramming in vivo is more efficient than in vitro, the influence of the extracellular microenvironment on cardiac reprogramming remains incompletely understood. This understanding is necessary to improve the efficiency of cardiac reprogramming in order to implement this strategy successfully. Here we have identified matrix identity and cell-generated tractional forces as key determinants of the dedifferentiation and differentiation stages during reprogramming. Cell proliferation, matrix mechanics, and matrix microstructure are also important, but play lesser roles. Our results suggest that the extracellular microenvironment can be optimized to enhance cardiac reprogramming. PMID:24326998

  3. Effects of Core Self-Evaluations on the Job Burnout of Nurses: The Mediator of Organizational Commitment

    PubMed Central

    Zhou, Yangen; Lu, Jiamei; Liu, Xianmin; Zhang, Pengcheng; Chen, Wuying

    2014-01-01

    Objective To explore the impact of Core self-evaluations on job burnout of nurses, and especially to test and verify the mediator role of organizational commitment between the two variables. Method Random cluster sampling was used to pick up participants sample, which consisted of 445 nurses of a hospital in Shanghai. Core self-evaluations questionnaire, job burnout scale and organizational commitment scale were administrated to the study participants. Results There are significant relationships between Core self-evaluations and dimensions of job burnout and organizational commitment. There is a significant mediation effect of organizational commitment between Core self-evaluations and job burnout. Conclusions To enhance nurses’ Core self-evaluations can reduce the incidence of job burnout. PMID:24755670

  4. Toward a Theory of Organizational Commitment.

    DTIC Science & Technology

    1981-08-01

    A0D-AI03 358 OREGON UNIV EUGENE GRADUATE SCHOOL OF MANAGEMENT AND--ETC F/0 5/1 TOWARD A THEORY OF ORGANIZATIONAL COMMITMENT.(U) AUG A1 R T MOWDAY, R...M STEERS, L W PORTER N00014-81-K 0026 UNCLASSIFIED TR-8 ML EhEE"hE hhEEE~EE7hhhh LEVEr / 00 Gradate choo of anagmen Univrsit of rego -VI Euee0reo 70...Oregon Eugene , OR 97403 Dr. Gerald R. Stoffer Aerospace Psychologist LT, Medical Service Corp. Code N-712 HAVTRAEQUIPCEN Orlando, FL 32813 Dr

  5. International Military Commitment: A Conceptual Definition

    DTIC Science & Technology

    1975-01-01

    commitments chiefly in military terms--most recently, in terms of the threat to our interest posed by the Soviet Union and by Communist China" (1973...nd accurate the poli t i c i t, n policy o 198 0’s wi1 i (Sprout i.arch 25/ ns, Europea t i-polar condi t ions h y d i fferont f...behavior had been effected -- if only crudely and at a very basic level. A nuclear weapons duopoly by the Lmited States and the Soviet Union and a less

  6. Regression of Pathological Cardiac Hypertrophy: Signaling Pathways and Therapeutic Targets

    PubMed Central

    Hou, Jianglong; Kang, Y. James

    2012-01-01

    Pathological cardiac hypertrophy is a key risk factor for heart failure. It is associated with increased interstitial fibrosis, cell death and cardiac dysfunction. The progression of pathological cardiac hypertrophy has long been considered as irreversible. However, recent clinical observations and experimental studies have produced evidence showing the reversal of pathological cardiac hypertrophy. Left ventricle assist devices used in heart failure patients for bridging to transplantation not only improve peripheral circulation but also often cause reverse remodeling of the geometry and recovery of the function of the heart. Dietary supplementation with physiologically relevant levels of copper can reverse pathological cardiac hypertrophy in mice. Angiogenesis is essential and vascular endothelial growth factor (VEGF) is a constitutive factor for the regression. The action of VEGF is mediated by VEGF receptor-1, whose activation is linked to cyclic GMP-dependent protein kinase-1 (PKG-1) signaling pathways, and inhibition of cyclic GMP degradation leads to regression of pathological cardiac hypertrophy. Most of these pathways are regulated by hypoxia-inducible factor. Potential therapeutic targets for promoting the regression include: promotion of angiogenesis, selective enhancement of VEGF receptor-1 signaling pathways, stimulation of PKG-1 pathways, and sustention of hypoxia-inducible factor transcriptional activity. More exciting insights into the regression of pathological cardiac hypertrophy are emerging. The time of translating the concept of regression of pathological cardiac hypertrophy to clinical practice is coming. PMID:22750195

  7. Cardiac radiology: centenary review.

    PubMed

    de Roos, Albert; Higgins, Charles B

    2014-11-01

    During the past century, cardiac imaging technologies have revolutionized the diagnosis and treatment of acquired and congenital heart disease. Many important contributions to the field of cardiac imaging were initially reported in Radiology. The field developed from the early stages of cardiac imaging, including the use of coronary x-ray angiography and roentgen kymography, to nowadays the widely used echocardiographic, nuclear medicine, cardiac computed tomographic (CT), and magnetic resonance (MR) applications. It is surprising how many of these techniques were not recognized for their potential during their early inception. Some techniques were described in the literature but required many years to enter the clinical arena and presently continue to expand in terms of clinical application. The application of various CT and MR contrast agents for the diagnosis of myocardial ischemia is a case in point, as the utility of contrast agents continues to expand the noninvasive characterization of myocardium. The history of cardiac imaging has included a continuous process of advances in our understanding of the anatomy and physiology of the cardiovascular system, along with advances in imaging technology that continue to the present day.

  8. Cardiac Trauma: Clinical and Experimental Correlations of Myocardial Contusion

    PubMed Central

    Doty, Donald B.; Anderson, Alan E.; Rose, Earl F.; Go, Raymundo T.; Chiu, Chiang L.; Ehrenhaft, J. L.

    1974-01-01

    Clinical and experimental observations in myocardial contusion have been correlated. Cardiac arrhythmia is always an important consequence and may be fatal. Reduction in cardiac output often accompanies significant cardiac injury. The coronary arterial circulation is not interrupted and is generally enhanced to the area of injury. Healing of the injury under these circulatory conditions may result in patchy scarring and peculiar adynamic areas of myocardium. Early diagnosis of myocardial contusion may be aided using radionuclide imaging with 99mTc-Sn-polyphosphate. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8. PMID:4412327

  9. Cardiac involvement in a female carrier of Duchenne muscular dystrophy.

    PubMed

    Walcher, Thomas; Kunze, Markus; Steinbach, Peter; Sperfeld, Anne-Dorte; Burgstahler, Christof; Hombach, Vinzenz; Torzewski, Jan

    2010-02-04

    A 42 year-old female carrier of Duchenne muscular dystrophy (DMD) was referred with suspected subacute myocarditis and non-sustained ventricular tachycardia. Echochardiography and cardiac catheterization revealed severely reduced left ventricular function (LVF). Coronary artery disease was excluded. Cardiac magnetic resonance imaging showed transmural, intramural and subepicardial late gadolinium enhancement. Myocardial biopsy excluded viral infection and showed severe myopathic changes with abnormal expression of dystrophin and utrophin. Moleculargenetic analysis of the DMD gene revealed frameshift duplication of exon 2. The patient received conventional heart failure therapy, implantable cardioverter/defibrillator-implantation and prednisolone to attenuate cardiac degradation. 6 months later she had improved clinically though LVF was still severely reduced.

  10. Commitment and exploration as mechanisms of identity formation.

    PubMed

    Meeus, W; Iedema, J; Maassen, G H

    2002-06-01

    We report a two-wave longitudinal study of 1,571 Dutch adolescents concerning the role of commitment and exploration in identity development. We used the Utrecht-Groningen Identity Development Scale to measure commitment and exploration in the domains of relational and societal identity. Our results can be summarized in three points. (1) Commitment and exploration are related processes in the development of identity. Adolescents with strong commitments also frequently explore them, and adolescents with low exploration in general have weak commitments. (2) The longitudinal stability of commitment and exploration has a medium effect size. For relational identity the stability of commitment is greater than that of exploration, but this is not the case for societal identity. The explanation we give for the lack of this difference in stability between commitment and exploration in societal identity is that the formative period for societal identity comes primarily at the end of adolescence. In that connection, we conclude that for present-day Dutch adolescents the formation of relational identity probably precedes that of societal identity. (3) In neither identity domain is commitment predictive of exploration three years later, nor is the reverse the case. We conclude that no long-term developmental sequentiality of commitment and exploration was found, but the results do not rule out the possibility of short-term developmental sequentiality.

  11. Effects of Gender on Engineering Career Commitment

    NASA Astrophysics Data System (ADS)

    Barker, Anne M.

    Engineering has been one of the most difficult fields for 'women to enter and in which to succeed. Although the percentage of female engineers has Increased, women are still seriously underrcpresented in the workforce. This study examined the effect offender on career commitment, success, satisfaction, and involvement in engineering, and the effect of personality and work environment on these variables. Alumni from an engineering school in the northeastern United States were surveyed. The questionnaire was analyzed using statistical and descriptive methods to determine relationships among these variables. Women's commitment scores were lower than men's when controlled for other variables, including satisfaction and involvement. Men had longer tenure as engineers than women, even when controlled for year of graduation, professional engineering status, and number of children. Women did not leave engineering in different proportions than men, but they did earn significantly less despite controlling for year of graduation and number of hours worked weekly. Some gender differences in workplace experience were also found, including having colleagues act protectively, being mistaken for secretaries, and seeing men progress faster in their careers than equally qualified women.

  12. Rationales for the Lightning Launch Commit Criteria

    NASA Technical Reports Server (NTRS)

    Willett, John C. (Editor); Merceret, Francis J. (Editor); Krider, E. Philip; O'Brien, T. Paul; Dye, James E.; Walterscheid, Richard L.; Stolzenburg, Maribeth; Cummins, Kenneth; Christian, Hugh J.; Madura, John T.

    2016-01-01

    Since natural and triggered lightning are demonstrated hazards to launch vehicles, payloads, and spacecraft, NASA and the Department of Defense (DoD) follow the Lightning Launch Commit Criteria (LLCC) for launches from Federal Ranges. The LLCC were developed to prevent future instances of a rocket intercepting natural lightning or triggering a lightning flash during launch from a Federal Range. NASA and DoD utilize the Lightning Advisory Panel (LAP) to establish and develop robust rationale from which the criteria originate. The rationale document also contains appendices that provide additional scientific background, including detailed descriptions of the theory and observations behind the rationales. The LLCC in whole or part are used across the globe due to the rigor of the documented criteria and associated rationale. The Federal Aviation Administration (FAA) adopted the LLCC in 2006 for commercial space transportation and the criteria were codified in the FAA's Code of Federal Regulations (CFR) for Safety of an Expendable Launch Vehicle (Appendix G to 14 CFR Part 417, (G417)) and renamed Lightning Flight Commit Criteria in G417.

  13. CircRNA_000203 enhances the expression of fibrosis-associated genes by derepressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts

    PubMed Central

    Tang, Chun-Mei; Zhang, Ming; Huang, Lei; Hu, Zhi-qin; Zhu, Jie-Ning; Xiao, Zhen; Zhang, Zhuo; Lin, Qiu-xiong; Zheng, Xi-Long; -Yang, Min; Wu, Shu-Lin; Cheng, Jian-Ding; Shan, Zhi-Xin

    2017-01-01

    Circular RNAs (circRNAs) participate in regulating gene expression in diverse biological and pathological processes. The present study aimed to investigate the mechanism underlying the modulation of circRNA_000203 on expressions of fibrosis-associated genes in cardiac fibroblasts. CircRNA_000203 was shown upregulated in the diabetic mouse myocardium and in Ang-II-induced mouse cardiac fibroblasts. Enforced-expression of circRNA_000203 could increase expressions of Col1a2, Col3a1 and α-SMA in mouse cardiac fibroblasts. RNA pull-down and RT-qPCR assay indicated that circRNA_000203 could specifically sponge miR-26b-5p. Dual luciferase reporter assay revealed that miR-26b-5p interacted with 3′UTRs of Col1a2 and CTGF, and circ_000203 could block the interactions of miR-26b-5p and 3′UTRs of Col1a2 and CTGF. Transfection of miR-26b-5p could post-transcriptionaly inhibit expressions of Col1a2 and CTGF, accompanied with the suppressions of Col3a1 and α-SMA in cardiac fibroblasts. Additionally, over-expression of circRNA_000203 could eliminate the anti-fibrosis effect of miR-26b-5p in cardiac fibroblasts. Together, our results reveal that suppressing the function of miR-26b-5p contributes to the pro-fibrosis effect of circRNA_000203 in cardiac fibroblasts. PMID:28079129

  14. Job Satisfaction, Organizational Commitment, and Religious Commitment of Full-Time University Employees

    ERIC Educational Resources Information Center

    Brown, Donna; Sargeant, Marcel A.

    2007-01-01

    This study investigated the relationship of job satisfaction and organizational and religious commitment among full time workers at Akra University (a pseudonym) based on a number of demographic factors. Analysis of variance using the Games-Howell procedure revealed that workers who were older than age 46 years had higher job satisfaction and…

  15. Employee Commitment in Context: The Nature and Implication of Commitment Profiles

    ERIC Educational Resources Information Center

    Meyer, John P.; Stanley, Laura J.; Parfyonova, Natalya M.

    2012-01-01

    It is well established that employee commitment can take different forms (e.g., affective, normative, and continuance), yet it is only recently that theory has been advanced to explain how these different forms combine to influence behavior (Meyer & Herscovitch, 2001). We tested this theory with data from employees in three human services…

  16. Fetal cardiac scanning today.

    PubMed

    Allan, Lindsey

    2010-07-01

    The ability to examine the structure of the fetal heart in real-time started over 30 years ago now. The field has seen very great advances since then, both in terms of technical improvements in ultrasound equipment and in dissemination of operator skills. A great deal has been learnt about normal cardiac function in the human fetus throughout gestation and how it is affected by pathologies of pregnancy. There is increasing recognition of abnormal heart structure during routine obstetric scanning, allowing referral for specialist diagnosis and counselling. It is now possible to make accurate diagnosis of cardiac malformations as early as 12 weeks of gestation. Early diagnosis of a major cardiac malformation in the fetus can provide the parents with a comprehensive prognosis, enabling them to make the most informed choice about the management of the pregnancy.

  17. Autoantibodies and Cardiac Arrhythmias

    PubMed Central

    Lee, Hon-Chi; Huang, Kristin T. L.; Wang, Xiao-Li; Shen, Win-Kuang

    2013-01-01

    Autoimmune diseases are associated with significant morbidity and mortality, afflicting about 5% of the population of the United States. They encompass a wide range of disorders that affect all organs of the human body and have a predilection for women. In the past, autoimmune pathogenesis was not thought to be a major mechanism for cardiovascular disorders, and potential relationships remain understudied. However, accumulating evidence suggests that a number of vascular and cardiac conditions are autoimmune-mediated. Recent studies indicate that autoantibodies play an important role in the development of cardiac arrhythmias, including atrial fibrillation, modulation of autonomic influences on heart rate and rhythm, conduction system abnormalities, and ventricular arrhythmias. This manuscript will review the current evidence for the role of autoantibodies in the development of cardiac arrhythmias. PMID:21740882

  18. Toothache of cardiac origin.

    PubMed

    Kreiner, M; Okeson, J P

    1999-01-01

    Pain referred to the orofacial structures can sometimes be a diagnostic challenge for the clinician. In some instances, a patient may complain of tooth pain that is completely unrelated to any dental source. This poses a diagnostic and therapeutic problem for the dentist. Cardiac pain most commonly radiates to the left arm, shoulder, neck, and face. In rare instances, angina pectoris may present as dental pain. When this occurs, an improper diagnosis frequently leads to unnecessary dental treatment or, more significantly, a delay of proper treatment. This delay may result in the patient experiencing an acute myocardial infarction. It is the dentist's responsibility to establish a proper diagnosis so that the treatment will be directed toward the source of pain and not to the site of pain. This article reviews the literature concerning referred pain of cardiac origin and presents a case report of toothache of cardiac origin.

  19. I say a little prayer for you: praying for partner increases commitment in romantic relationships.

    PubMed

    Fincham, Frank D; Beach, Steven R H

    2014-10-01

    Partner-focused petitionary prayer (PFPP) has received little attention in the prayer literature. In two studies, we examine PFPP to see whether it is uniquely important in conveying relationship benefits, whether its benefits are transmitted through an effect on relationship satisfaction, and whether one's own or the partner's PFPP is central to beneficial effects. In Study 1, we examined PFPP in a sample of 316 undergraduate students who were in an "exclusive" romantic relationship, finding that PFPP was related to later level of commitment and that this relationship was partially mediated through enhanced relationship satisfaction. Study 2 examined PFPP in a sample of 205, married African American couples, finding that both partners' PFPP was consequential for commitment, with actor effects partially mediated through relationship quality, and partner effects fully mediated. Together the studies suggest the value of continued investigation of PFPP as a potentially important vehicle for enhancing relationship outcomes.

  20. Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension.

    PubMed

    Martínez-Martínez, Ernesto; Calvier, Laurent; Fernández-Celis, Amaya; Rousseau, Elodie; Jurado-López, Raquel; Rossoni, Luciana V; Jaisser, Frederic; Zannad, Faiez; Rossignol, Patrick; Cachofeiro, Victoria; López-Andrés, Natalia

    2015-10-01

    Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension.

  1. Drug Treatment of Cardiac Failure

    PubMed Central

    Achong, M. R.; Kumana, C. R.

    1982-01-01

    Treatment of cardiac failure should first be aimed at reversing or ameliorating the underlying pathological processes. This review highlights the common problems and pitfalls in the use of digoxin, diuretics and vasodilators in patients with cardiac failure. PMID:21289849

  2. Mechanisms of cardiac arrhythmias

    PubMed Central

    Tse, Gary

    2015-01-01

    Blood circulation is the result of the beating of the heart, which provides the mechanical force to pump oxygenated blood to, and deoxygenated blood away from, the peripheral tissues. This depends critically on the preceding electrical activation. Disruptions in the orderly pattern of this propagating cardiac excitation wave can lead to arrhythmias. Understanding of the mechanisms underlying their generation and maintenance requires knowledge of the ionic contributions to the cardiac action potential, which is discussed in the first part of this review. A brief outline of the different classification systems for arrhythmogenesis is then provided, followed by a detailed discussion for each mechanism in turn, highlighting recent advances in this area. PMID:27092186

  3. Mechanisms of Cardiac Regeneration

    PubMed Central

    Uygur, Aysu; Lee, Richard T.

    2016-01-01

    Adult humans fail to regenerate their hearts following injury, and this failure to regenerate myocardium is a leading cause of heart failure and death worldwide. Although all adult mammals appear to lack significant cardiac regeneration potential, some vertebrates can regenerate myocardium throughout life. In addition, new studies indicate that mammals have cardiac regeneration potential during development and very soon after birth. The mechanisms of heart regeneration among model organisms, including neonatal mice, appear remarkably similar. Orchestrated waves of inflammation, matrix deposition and remodeling, and cardiomyocyte proliferation are commonly seen in heart regeneration models. Understanding why adult mammals develop extensive scarring instead of regeneration is a crucial goal for regenerative biology. PMID:26906733

  4. Sociosexual orientation, commitment, and infidelity: a mediation analysis.

    PubMed

    Mattingly, Brent A; Clark, Eddie M; Weidler, Daniel J; Bullock, Melinda; Hackathorn, Jana; Blankmeyer, Katheryn

    2011-01-01

    Individuals with an unrestricted sociosexual orientation (SO) are less committed to their romantic relationships and more likely to engage in infidelity. Furthermore, commitment is negatively associated with tendencies to cheat. However, no previous research has examined the possible mediating role of commitment in the relationship between SO and infidelity. The current study examined whether commitment mediated the relationship between SO and willingness to engage in three types of cheating behaviors (Ambiguous, Deceptive, and Explicit). Results suggested that commitment partially mediated the relationship between SO and infidelity, such that unrestricted individuals had lower commitment, which in turn led to a greater likelihood of cheating. Implications of this association and directions for future research are discussed.

  5. Conflicting pressures on romantic relationship commitment for anxiously attached individuals.

    PubMed

    Joel, Samantha; MacDonald, Geoff; Shimotomai, Atsushi

    2011-02-01

    Anxious attachment predicts strong desires for intimacy and stability in romantic relationships, yet the relation between anxious attachment and romantic commitment is unclear. We propose that extant literature has failed to find a consistent relation because anxiously attached individuals experience conflicting pressures on commitment. Data from Australia (N=137) show that relationship satisfaction and felt security each act as suppressors of a positive relation between anxious attachment and commitment. Data from Japan (N=159) replicate the suppression effect of felt security and also demonstrate that the residual positive relation between anxious attachment and commitment can be partly explained by dependence on the partner. These findings suggest that anxiously attached individuals may be ambivalent about commitment. Dissatisfaction and worries about negative evaluation appear to exert downward pressure on commitment, counteracting the upward pressure that is exerted by factors such as relational dependency.

  6. Experimental bit commitment based on quantum communication and special relativity.

    PubMed

    Lunghi, T; Kaniewski, J; Bussières, F; Houlmann, R; Tomamichel, M; Kent, A; Gisin, N; Wehner, S; Zbinden, H

    2013-11-01

    Bit commitment is a fundamental cryptographic primitive in which Bob wishes to commit a secret bit to Alice. Perfectly secure bit commitment between two mistrustful parties is impossible through asynchronous exchange of quantum information. Perfect security is however possible when Alice and Bob split into several agents exchanging classical and quantum information at times and locations suitably chosen to satisfy specific relativistic constraints. Here we report on an implementation of a bit commitment protocol using quantum communication and special relativity. Our protocol is based on [A. Kent, Phys. Rev. Lett. 109, 130501 (2012)] and has the advantage that it is practically feasible with arbitrary large separations between the agents in order to maximize the commitment time. By positioning agents in Geneva and Singapore, we obtain a commitment time of 15 ms. A security analysis considering experimental imperfections and finite statistics is presented.

  7. Emergency Cardiac Care: An Update

    PubMed Central

    Swanson, Richard W.

    1988-01-01

    The authors review the new guidelines for basic life support and advanced cardiac life support and the recommended changes to the standards. The changes recommended for basic life support will simplify the psychomotor skills required. The recommended changes to the guidelines for advanced cardiac life support, which include discontinuing the use of isoproterenol and limiting the use of sodium bicarbonate in cardiac arrest, are likely to improve survival rates. Controversies in the management of cardiac arrest are also discussed. PMID:21253157

  8. Which serial killers commit suicide? An exploratory study.

    PubMed

    Lester, David; White, John

    2012-11-30

    In a sample of 483 serial killers, 6.2% were documented to have committed suicide. Those who committed suicide were found to come from more dysfunctional homes characterized by more psychiatric disturbance in the parents. The sexual acts involved in the murders by the suicides seemed to be more deviant in some aspects, such as committing more bizarre sexual acts or more often taping the murder.

  9. Data analysis in cardiac arrhythmias.

    PubMed

    Rodrigo, Miguel; Pedrón-Torecilla, Jorge; Hernández, Ismael; Liberos, Alejandro; Climent, Andreu M; Guillem, María S

    2015-01-01

    Cardiac arrhythmias are an increasingly present in developed countries and represent a major health and economic burden. The occurrence of cardiac arrhythmias is closely linked to the electrical function of the heart. Consequently, the analysis of the electrical signal generated by the heart tissue, either recorded invasively or noninvasively, provides valuable information for the study of cardiac arrhythmias. In this chapter, novel cardiac signal analysis techniques that allow the study and diagnosis of cardiac arrhythmias are described, with emphasis on cardiac mapping which allows for spatiotemporal analysis of cardiac signals.Cardiac mapping can serve as a diagnostic tool by recording cardiac signals either in close contact to the heart tissue or noninvasively from the body surface, and allows the identification of cardiac sites responsible of the development or maintenance of arrhythmias. Cardiac mapping can also be used for research in cardiac arrhythmias in order to understand their mechanisms. For this purpose, both synthetic signals generated by computer simulations and animal experimental models allow for more controlled physiological conditions and complete access to the organ.

  10. Cardiac troponins and high-sensitivity cardiac troponin assays.

    PubMed

    Conrad, Michael J; Jarolim, Petr

    2014-03-01

    Measurement of circulating cardiac troponins I and T has become integral to the diagnosis of myocardial infarction. This article discusses the structure and function of the troponin complex and the release of cardiac troponin molecules from the injured cardiomyocyte into the circulation. An overview of current cardiac troponin assays and their classification according to sensitivity is presented. The diagnostic criteria, role, and usefulness of cardiac troponin for myocardial infarction are discussed. In addition, several examples are given of the usefulness of high-sensitivity cardiac troponin assays for short-term and long-term prediction of adverse events.

  11. [The publication and its commitment to the society].

    PubMed

    Fajardo-Gutiérrez, Arturo

    2014-01-01

    Publishing a research is one of the most important achievements for a researcher, since it is one of the tools to evaluate his scientific work. This achievement has a three-dimensional commitment: the personal commitment, the commitment with the population from which the data were obtained, and the commitment to the institution where he works. Therefore, publishing in the Revista Médica del Instituto Mexicano del Seguro Social should be a priority and an honor for a researcher of this Institution, since he is working with it to provide solutions to medical problems that affect their beneficiaries.

  12. F-MARC: promoting the prevention and management of sudden cardiac arrest in football

    PubMed Central

    Kramer, Efraim Benjamin; Dvorak, J; Schmied, C; Meyer, T

    2015-01-01

    Sudden cardiac death is the most common cause of unnatural death in football. To prevent and urgently manage sudden cardiac arrest on the football field-of-play, F-MARC (FIFA Medical and Research Centre) has been fully committed to a programme of research, education, standardisation and practical implementation. This strategy has detected football players at medical risk during mandatory precompetition medical assessments. Additionally, FIFA has (1) sponsored internationally accepted guidelines for the interpretation of an athlete's ECG, (2) developed field-of-play-specific protocols for the recognition, response, resuscitation and removal of a football player having sudden cardiac arrest and (3) introduced and distributed the FIFA medical emergency bag which has already resulted in the successful resuscitation of a football player who had a sudden cardiac arrest on the field-of-play. Recently FIFA, in association with the Institute of Sports and Preventive Medicine in Saarbrücken, Germany, established a worldwide Sudden Death Registry with a view to documenting fatal events on the football field-of-play. These activities by F-MARC are testimony to FIFA's continued commitment to minimising sudden cardiac arrest while playing football. PMID:25878076

  13. Resident cardiac progenitor cells: at the heart of regeneration.

    PubMed

    Bollini, Sveva; Smart, Nicola; Riley, Paul R

    2011-02-01

    Stem cell therapy has recently emerged as an innovative strategy over conventional cardiovascular treatments to restore cardiac function in patients affected by ischemic heart disease. Various stem cell populations have been tested and their potential for cardiac repair has been analyzed. Embryonic stem cells retain the greatest differentiation potential, but concerns persist with regard to their immunogenic and teratogenic effects. Although adult somatic stem cells are not tumourigenic and easier to use in an autologous setting, they exist in small numbers and possess reduced differentiation potential. Traditionally the heart was considered to be a post-mitotic organ; however, this dogma has recently been challenged with the identification of a reservoir of resident stem cells, defined as cardiac progenitor cells (CPCs). These endogenous progenitors may represent the best candidates for cardiovascular cell therapy, as they are tissue-specific, often pre-committed to a cardiac fate, and display a greater propensity to differentiate towards cardiovascular lineages. This review will focus on current research into the biology of CPCs and their regenerative potential. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

  14. Outpatient commitment and procedural due process.

    PubMed

    Player, Candice Teri-Lowe

    2015-01-01

    A large empirical literature on Kendra's Law has assessed the impact of court ordered outpatient treatment on outcomes such as treatment adherence, psychiatric hospitalization, quality of life, and treatment costs. Missing from the empirical literature, however, is a better understanding of procedural due process under Kendra's Law. Procedural due process concerns the safeguards that must be in place when governments deprive persons of their liberties, for example--notice, the right to a hearing and the right to appeal. This article reports the findings from a qualitative study of procedural due process and assisted outpatient treatment hearings under Kendra's Law. Attorneys reported significant barriers to effective advocacy on behalf of their clients. Further, despite the shift from a medical model of civil commitment to a judicial model in the 1970s, by and large judges continue to accord great deference to clinical testimony.

  15. Neuronal Polarity: Demarcation, growth and commitment

    PubMed Central

    Cáceres, Alfredo; Ye, Bing; Dotti, Carlos G.

    2012-01-01

    In a biological sense, polarity refers to the extremity of the main axis of an organelle, cell, or organism. In neurons, morphological polarity begins with the appearance of the first neurite from the cell body. In multipolar neurons, a second phase of polarization occurs when a single neurite initiates a phase of rapid growth to become the neuron’s axon, while the others later differentiate as dendrites. Finally, during a third phase, axons and dendrites develop an elaborate architecture, acquiring special morphological and molecular features that commit them to their final identities. Mechanistically, each phase must be preceded by spatial restriction of growth activity. We will review recent work on the mechanisms underlying the polarized growth of neurons. PMID:22726583

  16. Nanotechnology to drive stem cell commitment.

    PubMed

    Bressan, Eriberto; Carraro, Amedeo; Ferroni, Letizia; Gardin, Chiara; Sbricoli, Luca; Guazzo, Riccardo; Stellini, Edoardo; Roman, Marco; Pinton, Paolo; Sivolella, Stefano; Zavan, Barbara

    2013-03-01

    Stem cells (SCs) are undifferentiated cells responsible for the growth, homeostasis and repair of many tissues. The maintenance and survival of SCs is strongly influenced by several stimuli from the local microenvironment. The majority of signaling molecules interact with SCs at the nanoscale level. Therefore, scaffolds with surface nanostructures have potential applications for SCs and in the field of regenerative medicine. Although some strategies have already reached the field of cell biology, strategies based on modification at nanoscale level are new players in the fields of SCs and tissue regeneration. The introduction of the possibility to perform such modifications to these fields is probably due to increasing improvements in nanomaterials for biomedical applications, as well as new insights into SC biology. The aim of the present review is to exhibit the most recent applications of nanostructured materials that drive the commitment of adult SCs for potential clinical applications.

  17. Job Satisfaction and Organizational Commitment: Affective Commitment Predictors in a Group of Professionals

    NASA Astrophysics Data System (ADS)

    Ferretti, Maria Santa

    Job satisfaction and organizational commitment have long been identified as relevant factors for the well-being of individuals within an organization and the success of the organization itself. As the well-being can be, in principle, considered as emergent from the influence of a number of factors, the main goal of a theory of organizations is to identify these factors and the role they can play. In this regard job satisfaction and organizational commitment have been often identified with structural factors allowing an organization to be considered as a system, or a wholistic entity, rather than a simple aggregate of individuals. Furthermore, recent studies have shown that job satisfaction has a significant, direct effect on determining individuals' attachment to an organization and a significant but indirect effect on their intention to leave a company. However, a complete assessment of the role of these factors in establishing and keeping the emergence of an organization is still lacking, due to shortage of measuring instruments and to practical difficulties in interviewing organization members. The present study aims to give a further contribution to what is currently known about the relationship between job satisfaction and affective commitment by using a group of professionals, all at management level. A questionnaire to measure these constructs, following a pilot study, was designed and administered to 1042 participants who were all professionals and had the title of industrial manager or director. The factors relating to job satisfaction and the predictive value of these factors (to predict an employee's emotional involvement with their organization) were simultaneously tested by a confirmative factorial model. The results were generalized with a multi-sample procedure by using models of structural equations. This procedure was used to check whether these factors could be considered or not as causes producing the measured affective commitment. The results

  18. Self Enhancing Education: Handbook for Trainers.

    ERIC Educational Resources Information Center

    Randolph, Norma; And Others

    This Self Enhancing Education (SEE) trainng handbook gives suggestions for a 10 unit program. The training involves an introductory course of 30 hours, an advanced course of 30 hours, and a leaders course of 40 hours. Caution is given to the leader to allow the participants to commit themselves to SEE rather than the leader committing them, for…

  19. Cardiac T1 Imaging

    PubMed Central

    Jerosch-Herold, Michael; Kwong, Raymond Y.

    2014-01-01

    T1 mapping of the heart has evolved into a valuable tool to evaluate myocardial tissue properties, with or without contrast injection, including assessment of myocardial edema and free water content, extra-cellular volume (expansion), and most recently cardiomyocyte hypertrophy. The MRI pulse sequence techniques developed for these applications have had to address at least two important considerations for cardiac applications: measure magnetization inversion recoveries during cardiac motion with sufficient temporal resolution for the shortest expected T1 values, and, secondly, obtain these measurements within a time during which a patient can comfortably suspend breathing. So-called Look-Locker techniques, and variants thereof, which all sample multiple points of a magnetization recovery after each magnetization preparation have therefore become a mainstay in this field. The rapid pace of advances and new findings based on cardiac T1 mapping for assessment of diffuse fibrosis, or myocardial edema show that these techniques enrich the capabilities of MRI for myocardial tissue profiling, which is arguably unmatched by other cardiac imaging modalities. PMID:24509619

  20. Hepato-cardiac disorders

    PubMed Central

    Fouad, Yasser Mahrous; Yehia, Reem

    2014-01-01

    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases PMID:24653793

  1. Advanced Cardiac Life Support.

    ERIC Educational Resources Information Center

    Kirkwood Community Coll., Cedar Rapids, IA.

    This document contains materials for an advanced college course in cardiac life support developed for the State of Iowa. The course syllabus lists the course title, hours, number, description, prerequisites, learning activities, instructional units, required text, six references, evaluation criteria, course objectives by units, course…

  2. Ethical Issues in Cardiac Surgery

    PubMed Central

    Kavarana, Minoo N.; Sade, Robert M.

    2012-01-01

    While ethical behavior has always been part of cardiac surgical practice, ethical deliberation has only recently become an important component of cardiac surgical practice. Issues such as informed consent, conflict of interest, and professional self-regulation, among many others, have increasingly attracted the attention of cardiac surgeons. This review covers several broad topics of interest to cardiac surgeons and cardiologists, and treats several other topics more briefly. There is much uncertainty about what the future holds for cardiac surgical practice, research, and culture, and we discuss the background of ethical issues to serve as a platform for envisioning what is to come. PMID:22642634

  3. Commitment and self-control in a prisoner's dilemma game.

    PubMed

    Locey, Matthew L; Rachlin, Howard

    2012-07-01

    Humans often make seemingly irrational choices in situations of conflict between a particular smaller-sooner reinforcer and a more abstract, temporally extended, but larger reinforcer. In two experiments, the extent to which the availability of commitment responses-self-imposed restrictions on future choices-might improve self-control in such situations was investigated. Participants played a prisoner's dilemma game against a computer that played a tit-for-tat strategy-cooperating after a participant cooperated, defecting after a participant defected. Defecting produced a small-immediate reinforcer (consisting of points convertible to gift cards) whereas cooperating increased the amount of subsequent reinforcers, yielding a greater overall reinforcer rate. Participants were normally free to cooperate or defect on each trial. Additionally, they could choose to make a commitment response that forced their choice for the ensuing five trials. For some participants, the commitment response forced cooperation; for others, it forced defection. Most participants, with either commitment response available, chose to commit repeatedly despite a minor point loss for doing so. After extended exposure to these contingencies, the commit-to-cooperate group cooperated significantly more than a control group (with no commitment available). The commit-to-defect group cooperated significantly less than the control group. When both commitment alternatives were simultaneously available-one for cooperation and one for defection-cooperation commitment was strongly preferred. In Experiment 2, the commitment alternative was removed at the end of the session; gains in cooperation, relative to the control group, were not sustained in the absence of the self-imposed behavioral scaffold.

  4. Commit* to change? A call to end the publication of the phrase ‘commit* suicide’

    PubMed Central

    2016-01-01

    Background. Countering stigma is a fundamental facet of suicide prevention efforts.  Integral to this is the promotion of accurate and sensitive language.  The phrase ‘commit* suicide’ has prompted marked opposition primarily due to the connotations of immorality and illegality.  Methods. The study investigated the frequency of the use of the wordstem ‘commit’, in relation to self-harm and suicidal behaviours, in the three leading suicide-specific academic journals between 2000 and 2015.  Results. One third (34%) of articles published since the year 2000 used the word ‘commit*’ when describing an act of self-harm or suicide. Over half of these articles (57%) used the phrase on more than one occasion, with 6% using it more than 10 times in the same manuscript. The percentage of papers utilising the word ‘commit*’ has fluctuated over time, but there is a promising downward trend in the use of this phrase from 33% in 2000 to 13% in 2015 (p < 0.001).  Discussion. We advocate for the implementation of publication requirements regarding the language used when discussing suicide. Whilst we call for collective responsibility amongst academics and clinicians, editors hold a unique position in ensuring that outdated, inaccurate and stigma-laden terms are expunged from the scientific literature. PMID:28286872

  5. Genetics of sudden cardiac death.

    PubMed

    Bezzina, Connie R; Lahrouchi, Najim; Priori, Silvia G

    2015-06-05

    Sudden cardiac death occurs in a broad spectrum of cardiac pathologies and is an important cause of mortality in the general population. Genetic studies conducted during the past 20 years have markedly illuminated the genetic basis of the inherited cardiac disorders associated with sudden cardiac death. Here, we review the genetic basis of sudden cardiac death with a focus on the current knowledge on the genetics of the primary electric disorders caused primarily by mutations in genes encoding ion channels, and the cardiomyopathies, which have been attributed to mutations in genes encoding a broader category of proteins, including those of the sarcomere, the cytoskeleton, and desmosomes. We discuss the challenges currently faced in unraveling genetic factors that predispose to sudden cardiac death in the setting of sequela of coronary artery disease and present the genome-wide association studies conducted in recent years on electrocardiographic parameters, highlighting their potential in uncovering new biological insights into cardiac electric function.

  6. Symmetry of cardiac function assessment

    PubMed Central

    Bai, Xu-Fang; Ma, Amy X

    2016-01-01

    Both right and left ventricles are developed from two adjacent segments of the primary heart tube. Though they are different with regard to shape and power, they mirror each other in terms of behavior. This is the first level of symmetry in cardiac function assessment. Both cardiac muscle contraction and relaxation are active. This constructs the second level of symmetry in cardiac function assessment. Combination of the two levels will help to find some hidden indexes or approaches to evaluate cardiac function. In this article, four major indexes from echocardiography were analyzed under this principal, another seventeen indexes or measurement approaches came out of the shadow, which is very helpful in the assessment of cardiac function, especially for the right cardiac function and diastolic cardiac function. PMID:27582768

  7. Radiofrequency energy loop primes cardiac, neuronal, and skeletal muscle differentiation in mouse embryonic stem cells: a new tool for improving tissue regeneration.

    PubMed

    Maioli, Margherita; Rinaldi, Salvatore; Santaniello, Sara; Castagna, Alessandro; Pigliaru, Gianfranco; Gualini, Sara; Fontani, Vania; Ventura, Carlo

    2012-01-01

    Radiofrequency (RF) waves from Wi-Fi (wireless fidelity) technologies have become ubiquitous, with Internet access spreading into homes, and public areas. The human body harbors multipotent stem cells with various grading of potentiality. Whether stem cells may be affected by Wi-Fi RF energy remains unknown. We exposed mouse embryonic stem (ES) cells to a Radio Electric Asymmetric Conveyer (REAC), an innovative device delivering Wi-Fi RF of 2.4 GHz with its conveyer electrodes immersed into the culture medium. Cell responses were investigated by real-time PCR, Western blot, and confocal microscopy. Single RF burst duration, radiated power, electric and magnetic fields, specific absorption rate, and current density in culture medium were monitored. REAC stimulation primed transcription of genes involved in cardiac (GATA4, Nkx-2.5, and prodynorphin), skeletal muscle (myoD) and neuronal (neurogenin1) commitment, while downregulating the self renewal/pluripotency-associated genes Sox2, Oct4, and Nanog. REAC exposure enhanced the expression of cardiac, skeletal, and neuronal lineage-restricted marker proteins. The number of spontaneously beating ES-derived myocardial cells was also increased. In conclusion, REAC stimulation provided a "physical milieu" optimizing stem cell expression of pluripotentiality and the attainment of three major target lineages for regenerative medicine, without using chemical agonists or vector-mediated gene delivery.

  8. 10 CFR 609.8 - Term sheets and conditional commitments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Term sheets and conditional commitments. 609.8 Section 609.8 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS LOAN GUARANTEES FOR PROJECTS THAT EMPLOY INNOVATIVE TECHNOLOGIES § 609.8 Term sheets and conditional commitments. (a) DOE, after review...

  9. 49 CFR 611.11 - Local financial commitment criteria.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MAJOR CAPITAL INVESTMENT PROJECTS § 611.11 Local financial... proposed project is supported by an acceptable degree of local financial commitment, as required by section 5309(e)(1)(C). The local financial commitment to a proposed project will be evaluated according to...

  10. A Longitudinal Investigation of Commitment Dynamics in Cohabiting Relationships

    ERIC Educational Resources Information Center

    Rhoades, Galena K.; Stanley, Scott M.; Markman, Howard J.

    2012-01-01

    This longitudinal study followed 120 cohabiting, opposite-sex couples over 8 months to test hypotheses derived from commitment theory about how two types of commitment (dedication and constraint) operate during cohabitation. In nearly half the couples, there were large differences between partners in terms of dedication. These differences were…

  11. Teacher Team Commitment, Teamwork and Trust: Exploring Associations

    ERIC Educational Resources Information Center

    Park, Sungmin; Henkin, Alan B.; Egley, Robert

    2005-01-01

    Purpose: To investigate relationships between teamwork, trust and teacher team commitment. Design/methodology/approach: Research has confirmed the value-added effects of organizational commitment in terms of job performance, organizational effectiveness, and employee retention. This study focused on teacher teams as the unit of analysis, and…

  12. Commitment Contingencies in the Behavioral Treatment of Obesity.

    ERIC Educational Resources Information Center

    Norton, Richard S.; Powers, Richard B.

    Commitment is a self-control technique to induce weight loss. Tow targets of commitment contingencies, completion of the study and behavior change, were examined among 42 female and 3 male subjects who made a monetary deposit to enroll in the 10-week program. The treatment consisted of self-monitoring of eating and exercise behavior. Subjects were…

  13. The Five Commitments: A Philosophical Framework Manifested through Dance

    ERIC Educational Resources Information Center

    Wakamatsu, Kori

    2013-01-01

    The philosophical framework known as the Five Commitments was recently approved by the Governing Board of the Brigham Young University-Public School Partnership. The Five Commitments consist of: Civic Preparation and Engagement; Engaged Learning Through Nurturing Pedagogy; Equitable Access to Academic Knowledge and Achievement; Stewardship in…

  14. 38 CFR 36.4526 - Issuance of fund reservation commitments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... except with the written approval of the Department of Veterans Affairs. (b) Notwithstanding that direct... VETERANS AFFAIRS (CONTINUED) LOAN GUARANTY Direct Loans § 36.4526 Issuance of fund reservation commitments... eligible for direct loans may apply for a commitment for the reservation of direct loan funds to be...

  15. The Application of Acceptance and Commitment Therapy to Problem Anger

    ERIC Educational Resources Information Center

    Eifert, Georg H.; Forsyth, John P.

    2011-01-01

    The goal of this paper is to familiarize clinicians with the use of Acceptance and Commitment Therapy (ACT) for problem anger by describing the application of ACT to a case of a 45-year-old man struggling with anger. ACT is an approach and set of intervention technologies that support acceptance and mindfulness processes linked with commitment and…

  16. 46 CFR 308.5 - Voluntary contract of commitment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE General § 308.5 Voluntary contract of commitment. Applications for insurance on vessels described in § 308... obtained from the American War Risk Agency or MARAD. The effective date of the contract of commitment...

  17. Commitment, enjoyment and motivation in young soccer competitive players.

    PubMed

    Garcia-Mas, Alexandre; Palou, Pere; Gili, Margarita; Ponseti, Xavier; Borras, Pere A; Vidal, Josep; Cruz, Jaume; Torregrosa, Miquel; Villamarín, Francisco; Sousa, Catarina

    2010-11-01

    Building upon Deci's and Ryan (1985) Self-determination theory as well as the sportive behavioral correlates of the model of Commitment (Scanlan et al., 1976), this study tries to establish the relationship between motivation and commitment in youth sport. For this purpose 454 young competitive soccer players answered the Sport Motivation Scale (SMS) and the Sport Commitment Questionnaire (SCQ) during the regular season. The SMS measures the three dimensions of the Motivational continuum (the Amotivation, the Extrinsic Motivation and the Intrinsic Motivation). The SCQ measures the Sportive Commitment and its composing factors such as the Enjoyment, the Alternatives to the sport, and the Social Pressure. Our findings provided a clear pattern of the influence of motivation in sport enjoyment and commitment, outlining the positive contribution of intrinsic and extrinsic motivation to enjoyment and commitment. Amotivation, contributes positively to alternatives to sport and negatively to enjoyment and commitment, It should be noted that extrinsic motivation has a higher contribution to enjoyment whereas intrinsic motivation has a higher contribution to commitment.

  18. Commitment to Community Practice among Social Work Students: Contributing Factors

    ERIC Educational Resources Information Center

    Boehm, Amnon; Cohen, Ayala

    2013-01-01

    It is important to develop commitment to community practice among social work students to encourage their engagement in this field as professionals later in life. This research examines factors that affect commitment to community practice among social work students. A structured questionnaire was administered to 277 social work students in one…

  19. 48 CFR 3001.602-3 - Ratification of unauthorized commitments.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... unauthorized commitments. 3001.602-3 Section 3001.602-3 Federal Acquisition Regulations System DEPARTMENT OF... SYSTEM Career Development, Contracting Authority, and Responsibilities 3001.602-3 Ratification of unauthorized commitments. Department of Homeland Security (DHS) policy requires that acquisitions be made...

  20. 48 CFR 852.215-71 - Evaluation factor commitments.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Evaluation factor....215-71 Evaluation factor commitments. As prescribed in 815.304-71(b), insert the following clause: Evaluation Factor Commitments (DEC 2009) The offeror agrees, if awarded a contract, to use the...

  1. Toward a Theory of Commitment To Environmental Education Teaching.

    ERIC Educational Resources Information Center

    Shuman, Dorothea Kunz; Ham, Sam H.

    1997-01-01

    Addresses why some teachers are more committed than others to environmental education. Offers a theoretical perspective that links teachers' commitments to environmental education to significant life experiences and to beliefs and attitudes about teaching environmental concepts. Theoretical development led to a Model of Environmental Education…

  2. 40 CFR 52.238 - Commitment to undertake rulemaking.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Commitment to undertake rulemaking. 52.238 Section 52.238 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS California § 52.238 Commitment to...

  3. Unconditionally secure commitment in position-based quantum cryptography

    PubMed Central

    Nadeem, Muhammad

    2014-01-01

    A new commitment scheme based on position-verification and non-local quantum correlations is presented here for the first time in literature. The only credential for unconditional security is the position of committer and non-local correlations generated; neither receiver has any pre-shared data with the committer nor does receiver require trusted and authenticated quantum/classical channels between him and the committer. In the proposed scheme, receiver trusts the commitment only if the scheme itself verifies position of the committer and validates her commitment through non-local quantum correlations in a single round. The position-based commitment scheme bounds committer to reveal valid commitment within allocated time and guarantees that the receiver will not be able to get information about commitment unless committer reveals. The scheme works for the commitment of both bits and qubits and is equally secure against committer/receiver as well as against any third party who may have interests in destroying the commitment. Our proposed scheme is unconditionally secure in general and evades Mayers and Lo-Chau attacks in particular. PMID:25346509

  4. Principal Leadership and Organizational Commitment: The Principal Must Deliver.

    ERIC Educational Resources Information Center

    Tarter, C. John; And Others

    1989-01-01

    Theoretically, schools led by principals providing structure, resources, consideration, useful influence, and professional support in an even-handed, noncontrolling manner should be work places that elicit teacher commitment. This hypothesis was tested using a sample of 72 New Jersey secondary schools. Close control blunts teacher commitment.…

  5. Organisational Commitments and Teaching Styles among Academics in Mainland China

    ERIC Educational Resources Information Center

    Zhang, Li-Fang; Jing, Li-Zhen

    2016-01-01

    This research pioneered the investigation of the predictive power of organisational commitments for academics' teaching styles. Participants were 370 faculty members from 15 higher educational institutions in Beijing, the People's Republic of China. Results showed that academics' organisational commitments as measured by the Organisational…

  6. The Relationship between Perceived Organizational Support and Teachers' Organizational Commitment

    ERIC Educational Resources Information Center

    Nayir, Funda

    2012-01-01

    Problem Statement: It can be said that one of the key factors ensuring teachers adaptation to developments is teachers' level of commitment to their schools. In this commitment, the teacher is expected to internalize the organizational objectives. The teacher's perception of organizational support is important for him to internalize the…

  7. 17 CFR 229.1207 - (Item 1207) Delivery commitments.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false (Item 1207) Delivery... Gas Producing Activities § 229.1207 (Item 1207) Delivery commitments. (a) If the registrant is... delivery commitments; and (3) The steps that the registrant has taken to ensure that available reserves...

  8. Teachers: Emotional Intelligence, Job Satisfaction, and Organizational Commitment

    ERIC Educational Resources Information Center

    Anari, Nahid Naderi

    2012-01-01

    Purpose: The purpose of this study is to investigate the relationship between emotional intelligence and job satisfaction, between emotional intelligence and organizational commitment, and between job satisfaction and organizational commitment among high-school English teachers. Furthermore, the study aims to examine the role of gender and age in…

  9. Attachment and Commitment in College Students' Romantic Relationships.

    ERIC Educational Resources Information Center

    Pistole, M. Carole; Vocaturo, Loran C.

    1999-01-01

    Study examines attachment organization and dimensions of commitment in 101 females and 30 males with the use of an attachment questionnaire and the Commitment Inventory. Persons in a relationship who endorsed a secure or preoccupied attachment prototype reported stronger personal dedication than those endorsing a fearful-avoidant or…

  10. Primary Teacher Commitment and the Attractions of Teaching

    ERIC Educational Resources Information Center

    Troman, Geoff; Raggl, Andrea

    2008-01-01

    The article examines data collected from six primary schools in the ESRC Project: Primary Teacher Identity, Commitment and Career in Performative Cultures, and compares it to classic analyses of teacher commitment made by Dan Lortie and Jennifer Nias in order to assess continuity and change. The "mission" to teach is still there, as is…

  11. 37 CFR 251.38 - Billing and commitment to standards.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Billing and commitment to... PROCEDURE Standards of Conduct § 251.38 Billing and commitment to standards. (a) Arbitrators are bound by... abide by all the terms therein, including all of the standards of conduct and billing...

  12. 37 CFR 251.38 - Billing and commitment to standards.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Billing and commitment to... PROCEDURE Standards of Conduct § 251.38 Billing and commitment to standards. (a) Arbitrators are bound by... abide by all the terms therein, including all of the standards of conduct and billing...

  13. School Health and Its Relation to Teacher Commitment.

    ERIC Educational Resources Information Center

    Nir, Adam

    2002-01-01

    Examines the relationship between teacher commitment to school and students and organizational health, using survey data from 54 elementary schools in Israel. Finds, for example, that the principal's administrative behavior is the most significant predictor of teacher commitment. (Contains 50 references.) (PKP)

  14. Considerations in civil commitment of individuals with substance use disorders.

    PubMed

    Cavaiola, Alan A; Dolan, David

    2016-01-01

    Several states currently have enacted laws that allow for civil commitment for individuals diagnosed with severe substance use disorders. Civil commitment or involuntary commitment refers to the legal process by which individuals with mental illness are court-ordered into inpatient and/or outpatient treatment programs. Although initially civil commitment laws were intended for individuals with severe mental illness, these statutes have been extended to cover individuals with severe substance use disorders. Much of the recent legislation allowing for civil commitment of individuals with substance use disorders has come about in response to the heroin epidemic and is designed to provide an alternative to the unrelenting progression of opioid use disorders. Civil commitment also provides an opportunity for individuals with opioid use disorders to make informed decisions regarding ongoing or continued treatment. However, civil commitment also raises concerns regarding the potential violation of 14th Amendment rights, specifically pertaining to abuses of deprivation of liberty or freedom, which are guaranteed under the 14th Amendment to the United States Constitution. This commentary examines these issues while supporting the need for effective brief civil commitment legislation in all states.

  15. Generational Differences as a Determinant of Women's Perspectives on Commitment

    ERIC Educational Resources Information Center

    Stark, Marcella D.; Kirk, Amy Manning; Bruhn, Rick

    2012-01-01

    Differences between 116 graduate and undergraduate women, representing 4 generations (i.e., Baby Boomers, Transitionals, Generation Xers, and Millennials), were studied to categorize earliest awareness and definitions of commitment in relationships. More than 63% of participants in each generation viewed relationship commitment in terms of…

  16. The Relationship between Career Growth and Organizational Commitment

    ERIC Educational Resources Information Center

    Weng, Qingxiong; McElroy, James C.; Morrow, Paula C.; Liu, Rongzhi

    2010-01-01

    This research examines the relationship between employees' career growth and organizational commitment. Career growth was conceptualized by four factors: career goal progress, professional ability development, promotion speed and remuneration growth, while organizational commitment was conceptualized using Meyer and Allen's (1997) three component…

  17. What Factors Influence a Teacher's Commitment to Student Learning?

    ERIC Educational Resources Information Center

    Dannetta, Vincent

    2002-01-01

    Study of the personal, organizational, student-related factors influencing teacher commitment to student learning. Finds, for example, that among personal factors intrinsic rewards are more important than extrinsic rewards, that among organization factors collegiality is an important influence on commitment to student learning, and that among…

  18. Transferability of Skills and Education and Thai Academics' Organisational Commitment

    ERIC Educational Resources Information Center

    Rungruang, Parisa; Donohue, Ross

    2007-01-01

    Few studies have examined the links between perceived transferability of education or perceived transferability of skills and organisational commitment. This paper reports on a study examining the relationships between transferability of education and transferability of skills, and the three components of organisational commitment (affective,…

  19. 49 CFR 611.11 - Local financial commitment criteria.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Local financial commitment criteria. 611.11... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MAJOR CAPITAL INVESTMENT PROJECTS § 611.11 Local financial... proposed project is supported by an acceptable degree of local financial commitment, as required by...

  20. School-Based Management and Its Effect on Teacher Commitment.

    ERIC Educational Resources Information Center

    Nir, Adam E.

    2002-01-01

    Report of a study from Israel that reveals that SBM positively affects teachers' commitment to the profession and students' academic achievement, and negatively affects their commitment to the school and students' social well-being. Further, teachers' autonomy remained unchanged after SBM was introduced. (Contains 4 figures, a questionnaire, and…

  1. Investigation of the Relationship between Organizational Trust and Organizational Commitment

    ERIC Educational Resources Information Center

    Bastug, Gülsüm; Pala, Adem; Kumartasli, Mehmet; Günel, Ilker; Duyan, Mehdi

    2016-01-01

    Organizational trust and organizational commitment are considered as the most important entraining factors for organizational success. The most important factor in the formation of organizational commitment is trust that employees have in their organizations. In this study, the relationship between organizational trust and organizational…

  2. 48 CFR 2001.602-3 - Ratification of unauthorized commitments.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... unauthorized commitments. 2001.602-3 Section 2001.602-3 Federal Acquisition Regulations System NUCLEAR... Authority and Responsibilities 2001.602-3 Ratification of unauthorized commitments. (a) The Government is..., all other terms of subpart 2001.6 are applicable. All ratification actions exceeding $2,500 shall...

  3. 48 CFR 2001.602-3 - Ratification of unauthorized commitments.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... unauthorized commitments. 2001.602-3 Section 2001.602-3 Federal Acquisition Regulations System NUCLEAR... Authority and Responsibilities 2001.602-3 Ratification of unauthorized commitments. (a) The Government is..., all other terms of subpart 2001.6 are applicable. All ratification actions exceeding $2,500 shall...

  4. 48 CFR 2001.602-3 - Ratification of unauthorized commitments.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... unauthorized commitments. 2001.602-3 Section 2001.602-3 Federal Acquisition Regulations System NUCLEAR... Authority and Responsibilities 2001.602-3 Ratification of unauthorized commitments. (a) The Government is..., all other terms of subpart 2001.6 are applicable. All ratification actions exceeding $2,500 shall...

  5. 48 CFR 2001.602-3 - Ratification of unauthorized commitments.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... unauthorized commitments. 2001.602-3 Section 2001.602-3 Federal Acquisition Regulations System NUCLEAR... Authority and Responsibilities 2001.602-3 Ratification of unauthorized commitments. (a) The Government is..., all other terms of subpart 2001.6 are applicable. All ratification actions exceeding $2,500 shall...

  6. 48 CFR 2001.602-3 - Ratification of unauthorized commitments.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... unauthorized commitments. 2001.602-3 Section 2001.602-3 Federal Acquisition Regulations System NUCLEAR... Authority and Responsibilities 2001.602-3 Ratification of unauthorized commitments. (a) The Government is..., all other terms of subpart 2001.6 are applicable. All ratification actions exceeding $2,500 shall...

  7. Impact of Satisfaction and Commitment on Teachers' Organizational Citizenship

    ERIC Educational Resources Information Center

    Sesen, Harun; Basim, Nejat H.

    2012-01-01

    This study examined the impact of job satisfaction and organizational commitment on teachers' organizational citizenship behavior (OCB) in a structural equation model. The study was employed to a group of teachers and their supervisors. The results indicated that job satisfaction and commitment to the school had an impact on OCBs of the teachers…

  8. Regulation of cardiac function during a cold pressor test in athletes and untrained subjects.

    PubMed

    Ifuku, Hirotoshi; Moriyama, Kayo; Arai, Kuniko; Shiraishi-Hichiwa, Yumiko

    2007-09-01

    By using (dP/dt)/P of carotid artery pulse, a non-invasive index of cardiac contractility, we examined the regulatory mechanism of cardiac function during a cold pressor test in athletes and untrained subjects. Twenty-four healthy subjects (9 athletes, 8 untrained subjects, and 7 hyperreactors of 4 athletes and 3 untrained subjects with a rise of 15 mmHg or greater in systolic and/or diastolic blood pressure) underwent the cold pressor test according to Hines and Brown (Am Heart J 11:1-9, 1936): immersion of the right hand in 4 degrees C water for 1 min. Although mean blood pressure increased during the cold stress in all the groups, cardiac function differed. In athletes, heart rate and cardiac contractility caused cardiac output to increase while total peripheral resistance (TPR) did not change. In untrained subjects, however, heart rate and cardiac contractility tended to decrease cardiac output and thus TPR increased. In hyperreactors, heart rate and cardiac contractility increased during cold stress, and also TPR increased. After the end of the test, heart rate and cardiac contractility decreased only in untrained group. The findings that during a cold pressor test heart rate and cardiac contractility are enhanced in athletes but depressed in untrained subjects indicate that the state of physical training influences cardiac sympathetic neural reactivity to cold stress, except for hyperreactors.

  9. Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis

    PubMed Central

    Treibel, Thomas A.; Bandula, Steve; Fontana, Marianna; White, Steven K.; Gilbertson, Janet A.; Herrey, Anna S.; Gillmore, Julian D.; Punwani, Shonit; Hawkins, Philip N.; Taylor, Stuart A.; Moon, James C.

    2015-01-01

    Background Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. Objectives To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. Methods Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). Results ECVCT and ECVCMR results were well correlated (r2 = 0.85 vs r2 = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001). Conclusion Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis. PMID:26209459

  10. Inhalant-Abuse Myocarditis Diagnosed by Cardiac Magnetic Resonance

    PubMed Central

    Rao, Krishnasree; Matulevicius, Susan

    2016-01-01

    Multiple reports of toxic myocarditis from inhalant abuse have been reported. We now report the case of a 23-year-old man found to have toxic myocarditis from inhalation of a hydrocarbon. The diagnosis was made by means of cardiac magnetic resonance imaging with delayed enhancement. The use of cardiac magnetic resonance to diagnose myocarditis has become increasingly common in clinical medicine, although there is not a universally accepted criterion for diagnosis. We appear to be the first to document a case of toxic myocarditis diagnosed by cardiac magnetic resonance. In patients with a history of drug abuse who present with clinical findings that suggest myocarditis or pericarditis, cardiac magnetic resonance can be considered to support the diagnosis. PMID:27303242

  11. Representations of spacetime: Formalism and ontological commitment

    NASA Astrophysics Data System (ADS)

    Bain, Jonathan Stanley

    This dissertation consists of two parts. The first is on the relation between formalism and ontological commitment in the context of theories of spacetime, and the second is on scientific realism. The first part begins with a look at how the substantivalist/relationist debate over the ontological status of spacetime has been influenced by a particular mathematical formalism, that of tensor analysis on differential manifolds (TADM). This formalism has motivated the substantivalist position known as manifold substantivalism. Chapter 1 focuses on the hole argument which maintains that manifold substantivalism is incompatible with determinism. I claim that the realist motivations underlying manifold substantivalism can be upheld, and the hole argument avoided, by adopting structural realism with respect to spacetime. In this context, this is the claim that it is the structure that spacetime points enter into that warrants belief and not the points themselves. In Chapter 2, an elimination principle is defined by means of which a distinction can be made between surplus structure and essential structure with respect to formulations of a theory in two distinct mathematical formulations and some prior ontological commitments. This principle is then used to demonstrate that manifold points may be considered surplus structure in the formulation of field theories. This suggests that, if we are disposed to read field theories literally, then, at most, it should be the essential structure common to all alternative formulations of such theories that should be taken literally. I also investigate how the adoption of alternative formalisms informs other issues in the philosophy of spacetime. Chapter 3 offers a realist position which takes a semantic moral from the preceding investigation and an epistemic moral from work done on reliability. The semantic moral advises us to read only the essential structure of our theories literally. The epistemic moral shows us that such structure

  12. Ideological commitment and posttraumatic stress in former Tamil child soldiers.

    PubMed

    Kanagaratnam, Pushpa; Raundalen, Magne; Asbjørnsen, Arve E

    2005-12-01

    This study focuses on the impact of present ideological commitment on posttraumatic stress symptoms in former child soldiers living in exile. Eighteen men and two women (aged 25-37), who had joined different Tamil armed groups in Sri Lanka between the ages of 13 and 17 years, participated. The Impact of Event Scale was used to measure posttraumatic symptoms. Qualitative methods were used to investigate the participants' ideological commitment. Participants reported being exposed to many potentially traumatizing events, and had high scores on the Impact of Event Scale. Twenty-five percent of the sample showed strong ideological commitment to the "cause". Ideological commitment at the present seemed to predict better mental health when exposure was less intense and overwhelming. Time had a negative impact on ideological commitment.

  13. Exploring commitment, professional identity, and support for student nurses.

    PubMed

    Clements, Andrew James; Kinman, Gail; Leggetter, Sandra; Teoh, Kevin; Guppy, Andrew

    2016-01-01

    Problems with the recruitment and retention of nurses globally mean that insight into the factors that might increase retention in qualified staff and students is crucial. Despite clear links between work commitment and retention, there is little research exploring commitment in student nurses and midwives. This paper reports the findings of a qualitative study designed to provide insight into commitment using semi-structured interviews conducted with nine pre-registration students and a qualitative survey completed by 171 pre-registration students. Thematic analysis of the data emphasised the impact of placement experiences on commitment via interpersonal relationships. Students typically emphasised their professional identity as the basis for commitment, although many participants also highlighted a lack of acceptance by qualified practitioners, which reduced it. There was evidence that suggested that practitioner workload may impact the student experience due to challenges in making sufficient time to provide support. Implications for retention strategies are discussed.

  14. Nurses' perception of ethical climate and organizational commitment.

    PubMed

    Borhani, Fariba; Jalali, Tayebe; Abbaszadeh, Abbas; Haghdoost, Aliakbar

    2014-05-01

    The high turnover of nurses has become a universal issue. The manner in which nurses view their organization's ethical climate has direct bearing on their organizational commitment. The aim of this study was to determine the correlation between nurses' perception of ethical climate and organizational commitment in teaching hospitals in the southeastern region of Iran. A descriptive analytical design was used in this study. The sample consisted of 275 nurses working in four teaching hospitals in the southeastern region of Iran. The instruments used in this study included a demographic questionnaire, Ethical Climate Questionnaire, and Organizational Commitment Questionnaire. Data analysis was carried out using Pearson's correlation, t-test, and descriptive statistic through Statistical Package for Social Science, version 16. The result of this research indicated a positive correlation among professionalism, caring, rules, independence climate, and organizational commitment. Therefore, findings of this study are a guideline for researchers and managers alike who endeavor to improve organizational commitment.

  15. Bidirectional ventricular tachycardia in cardiac sarcoidosis.

    PubMed

    Benjamin, Mina M; Hayes, Kevin; Field, Michael E; Scheinman, Melvin M; Hoffmayer, Kurt S

    2017-02-01

    A 73-year-old man with history of pulmonary sarcoidosis was found to have runs of non-sustained bidirectional ventricular tachycardia (BVT) with two different QRS morphologies on a Holter monitor. Cardiac magnetic resonance delayed gadolinium imaging revealed a region of patchy mid-myocardial enhancement within the left ventricular basal inferolateral myocardium. An 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased uptake in the same area, consistent with active sarcoid, with no septal involvement. Follow-up FDG-PET one year later showed disease progression with new septal involvement. Cardiac sarcoidosis, characterized by myocardial inflammation and interstitial fibrosis that can lead to conduction system disturbance and macro re-entrant arrhythmias, should be considered in differential diagnosis of BVT. BVT may indicate septal involvement with sarcoidosis before the lesions are large enough to be detected radiologically.

  16. Cardiac arrhythmias in pregnancy.

    PubMed

    Knotts, Robert J; Garan, Hasan

    2014-08-01

    As more women with repaired congenital heart disease survive to their reproductive years and many other women are delaying pregnancy until later in life, a rising concern is the risk of cardiac arrhythmias during pregnancy. Naturally occurring cardiovascular changes during pregnancy increase the likelihood that a recurrence of a previously experienced cardiac arrhythmia or a de novo arrhythmia will occur. Arrhythmias should be thoroughly investigated to determine if there is a reversible etiology, and risks/benefits of treatment options should be fully explored. We discuss the approach to working up and treating various arrhythmias during pregnancy with attention to fetal and maternal risks as well as treatment of fetal arrhythmias. Acute management in stable patients includes close monitoring and intravenous pharmacologic therapy, while DC cardioversion should be used to terminate arrhythmias in hemodynamically unstable patients. Long-term management may require continued oral antiarrhythmic therapy, with particular attention to fetal safety, to prevent complications associated with arrhythmias.

  17. Practical cardiac auscultation.

    PubMed

    Shindler, Daniel M

    2007-01-01

    This article focuses on the practical use of the stethoscope. The art of the cardiac physical examination includes skillful auscultation. The article provides the author's personal approach to the patient for the purpose of best hearing, recognizing, and interpreting heart sounds and murmurs. It should be used as a brief introduction to the art of auscultation. This article also attempts to illustrate heart sounds and murmurs by using words and letters to phonate the sounds, and by presenting practical clinical examples where auscultation clearly influences cardiac diagnosis and treatment. The clinical sections attempt to go beyond what is available in standard textbooks by providing information and stethoscope techniques that are valuable and useful at the bedside.

  18. Cardiac nuclear medicine

    SciTech Connect

    Gerson, M.C.

    1987-01-01

    The book begins with a review of the radionuclide methods available for evaluating cardiac perfusion and function. The authors discuss planar and tomographic thallium myocardial imaging, first-pass and equilibrium radionuclide angiography, and imaging with infarct-avid tracers. Several common but more specialized procedures are then reviewed: nonogemetric measurement of left ventricular volume, phase (Fourier) analysis, stroke volume ratio, right ventricular function, and diastolic function. A separate chapter is devoted to drug interventions and in particular the use of radionuclide ventriculography to monitor doxorubicin toxicity and therapy of congestive heart failure. The subsequent chapters provide a comprehensive guide to test selection, accuracy, and results in acute myocardial infarction, in postmyocardial infarction, in chronic coronary artery disease, before and after medical or surgical revascularization, in valvular heart disease, in cardiomyopathies, and in cardiac trauma.

  19. Facility's employment practices reflect affirmative action commitment.

    PubMed

    Glaser, J W; Madden, M J

    1984-04-01

    The U.S. bishops' statements on racism over the last 40 years have addressed the structural as well as the personal aspects of racial discrimination. They have noted its persistence, described it as a moral and religious problem, and called for aggressive action among Catholics to combat it. "Meaningful equality" for blacks, however, remains a distant dream, the U.S. Supreme Court noted in a recent case involving institutional discrimination, because of the basically disadvantaged position into which blacks are born. As statistics on health, education, work, and standard of living illustrate, the socioeconomic opportunities available to blacks are markedly lower than those available to white Americans. Despite these odds, efforts to improve blacks' chances of contributing to society--through affirmative action programs--have achieved striking results in industry. Hospitals, as major workplaces, likewise should focus greater attention on developing and extending minority employment and advancement programs. Catholic health care facilities especially should evaluate their commitments to affirmative action. Increased efforts to eliminate discrimination in all aspects of a hospital's relationships with the business community as well as with its own employees will cause them to be recognized as symbols of justice not only in the workplace but also in society.

  20. Cellular commitment in the developing cerebellum

    PubMed Central

    Marzban, Hassan; Del Bigio, Marc R.; Alizadeh, Javad; Ghavami, Saeid; Zachariah, Robby M.; Rastegar, Mojgan

    2014-01-01

    The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways. In this review, we will highlight the anatomical structure of human and mouse cerebellum, the cellular composition of developing cerebellum, and the underlying gene expression programs involved in cell fate commitments in the cerebellum. A critical evaluation of the cell death literature suggests that apoptosis occurs in ~5% of cerebellar cells, most shortly after mitosis. Apoptosis and cellular autophagy likely play significant roles in cerebellar development, we provide a comprehensive discussion of their role in cerebellar development and organization. We also address the possible function of unfolded protein response in regulation of cerebellar neurogenesis. We discuss recent advancements in understanding the epigenetic signature of cerebellar compartments and possible connections between DNA methylation, microRNAs and cerebellar neurodegeneration. Finally, we discuss genetic diseases associated with cerebellar dysfunction and their role in the aging cerebellum. PMID:25628535