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Sample records for human heart enhancers

  1. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

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    Kaytlyn A Gerbin

    Full Text Available Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz. Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they

  2. Human heart by art.

    Science.gov (United States)

    Tamir, Abraham

    2012-11-01

    Heart is of great importance in maintaining the life of the body. Enough to stop working for a few minutes to cause death, and hence the great importance in physiology, medicine, and research. This fact was already emphasized in the Bible in the Book of Proverbs, chapter 4 verse 23: "Keep your heart with all diligence, for out of it is the wellspring of life." Art was able to demonstrate the heart from various aspects; realistically, as done by Leonardo de Vinci who demonstrated the halves of the heart and its blood vessels. Symbolically, as a source of life, the heart was demonstrated by the artist Mrs. Erlondeiel, as a caricature by Salvador Dali, as an open heart by Sawaya, etc. Finally, it should be emphasized that different demonstrations of the human heart by many artworks make this most important organ of our body (that cannot be seen from outside) more familiar and clearer to us. And this is the purpose of this article-to demonstrate the heart through a large number of artworks of different kinds.

  3. Practical training on porcine hearts enhances students' knowledge of human cardiac anatomy.

    Science.gov (United States)

    Musumeci, Giuseppe; Loreto, Carla; Mazzone, Venera; Szychlinska, Marta Anna; Castrogiovanni, Paola; Castorina, Sergio

    2014-05-01

    Historically, cadavers have been used for the study of anatomy. Nowadays, the territorial and legal limitations of this approach have led to the introduction of alternative teaching methods such as the use of practical exercise consisting of dissection and observation of animal organs. The aim of this study was to evaluate the use of practical training on animal organs compared with the traditional method of anatomy teaching, based on the dissection of human cadavers. In this study, we seek to demonstrate the usefulness of practical exercise on animal organs. This practical training was held a week after the series of lectures, thus leaving time for the students to learn and understand the topics discussed. Immediately after the lecture, all of the students completed a preliminary test to assess the immediate effect of the lecture. Immediately before the practical exercise, both control and experimental groups completed a second test to assess the effectiveness of personal study. Immediately after practical training, a third test was completed by the experimental group and the control group (no practical activity on animal organs) to highlight the added value of hands-on practice in addition to the lecture. Data obtained from statistical analysis showed a panatomy learning between control and experimental groups. Thus, the results of this study emphasize the utility of practical training on animal organs in learning and understanding anatomy, considering the limitations of the use of cadavers. Copyright © 2014 Elsevier GmbH. All rights reserved.

  4. ChIP-seq Identification of Weakly Conserved Heart Enhancers

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    Blow, Matthew J.; McCulley, David J.; Li, Zirong; Zhang, Tao; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Chen, Feng; Afzal, Veena; Bristow, James; Ren, Bing; Black, Brian L.; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.

    2010-07-01

    Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme non-coding sequence conservation successfully predicts enhancers active in many tissues, but fails to identify substantial numbers of heart enhancers. Here we used ChIP-seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over three thousand candidate heart enhancers genome-wide. Compared to other tissues studied at this time-point, most candidate heart enhancers are less deeply conserved in vertebrate evolution. Nevertheless, the testing of 130 candidate regions in a transgenic mouse assay revealed that most of them reproducibly function as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary constraint of embryonic enhancers can vary depending on tissue type.

  5. Defining Human Enhancement

    DEFF Research Database (Denmark)

    Nordberg, Ana

    2017-01-01

    -matter definitions are vital legal tools to determine what is currently regulated in established fields of law and whether there is room for a new legal field – Enhancement Law. This paper provides a reflection on the relevance of establishing a legal definition of human enhancement and to what extent different...... legal fields and jurisdictions may warrant different understandings of such concept. It reviews a number of different and often divergent concepts and taxonomies of human enhancement and concludes with the proposal and analysis of a definition: Use of technological means with the intention to improve......Emerging technologies open the prospect of extraordinary interventions on the human body. These may go beyond what is strictly necessary to sustain health and well-being. While responding to social and ethical challenges of such advances, the Law simultaneously faces the challenge of reflecting...

  6. Total excitation of the isolated human heart

    NARCIS (Netherlands)

    Durrer, D.; Dam, R.Th. van; Freud, G.E.; Janse, M.J.; Meijler, F.L.; Arzbaecher, R.C.

    To obtain information conceming the time course and instantaneous distribution of the excitatory process of the normal human healt, studies were made on isolated human hearts from seven individuals who died from various cerebral conditions, but who had no history of cardiac disease. Measurements

  7. Human freedom and enhancement.

    Science.gov (United States)

    Heilinger, Jan-Christoph; Crone, Katja

    2014-02-01

    Ideas about freedom and related concepts like autonomy and self-determination play a prominent role in the moral debate about human enhancement interventions. However, there is not a single understanding of freedom available, and arguments referring to freedom are simultaneously used to argue both for and against enhancement interventions. This gives rise to misunderstandings and polemical arguments. The paper attempts to disentangle the different distinguishable concepts, classifies them and shows how they relate to one another in order to allow for a more structured and clearer debate. It concludes in identifying the individual underpinnings and the social conditions of choice and decision-making as particularly salient dimensions of freedom in the ethical debate about human enhancement.

  8. Pig models for the human heart failure syndrome

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Terzic, Dijana; Zois, Nora Elisabeth

    2014-01-01

    Human heart failure remains a challenging illness despite advances in the diagnosis and treatment of heart failure patients. There is a need for further improvement of our understanding of the failing myocardium and its molecular deterioration. Porcine models provide an important research tool...... in this respect as molecular changes can be examined in detail, which is simply not feasible in human patients. However, the human heart failure syndrome is based on symptoms and signs, where pig models mostly mimic the myocardial damage, but without decisive data on clinical presentation and, therefore, a heart...... to elucidate the human heart failure syndrome....

  9. ILK induces cardiomyogenesis in the human heart.

    Directory of Open Access Journals (Sweden)

    Alexandra Traister

    Full Text Available Integrin-linked kinase (ILK is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart.Primary cultures of human fetal myocardial cells (19-22 weeks gestation yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43 and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001. The number of cardioblast colonies was significantly decreased (p<0.05 when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT. The cardiomyogenic effects of ILK(R211A and ILK(WT were accompanied by concurrent activation of β-catenin (p<0.001 and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A and ILK(WT. Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs.In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for

  10. Indulging anxiety: human enhancement from a Protestant perspective.

    Science.gov (United States)

    Hanson, Mark J

    1999-08-01

    At the heart of any ethics of human enhancement must be some normative assumptions about human nature. The purpose of this essay is to draw on themes from a Protestant theological anthropology to provide a basis for understanding and evaluating the tension between maintaining our humanity and enhancing it. Drawing primarily on the work of theologian Reinhold Niebuhr, I interpret enhancement as proceeding from the anxiety that characterizes human experience at the juncture of freedom and finiteness. Religious and moral dimensions of human sinfulness are considered in relation to cultural values that motivate human enhancement generally. I employ these dimensions in a series of benchmarks to suggest a background of theological, anthropological, and moral considerations against which enhancement is not to be condemmed but rather critically evaluated.

  11. Restoration of heart functions using human embryonic stem cells derived heart muscle cells.

    Science.gov (United States)

    Gepstein, Lior; Kehat, Izhak

    2005-02-01

    Extract: Recent advances in molecular and cellular biology and specifically in the areas of stem cell biology and tissue engineering have paved the way for the development of a new field in biomedicine, regenerative medicine. This exciting approach seeks to develop new biological solutions, using the mobilization of endogenous stem cells or delivery of exogenous cells to replace or modify the function of diseased, absent, or malfunctioning tissue. The adult heart represents an attractive candidate for these emerging technologies, since adult cardiomyocytes have limited regenerative capacity. Thus, any significant heart cell loss or dysfunction, such as occurs during heart attack, is mostly irreversible and may lead to the development of progressive heart failure, one of the leading causes of world-wide morbidity and mortality. Similarly, dysfunction of the specialized electrical conduction system within the heart may result in inefficient rhythm initiation or impulse conduction, leading to significant slowing of the heart rate, usually requiring the implantation of a permanent electronic pacemaker. Replacement of the dysfunctional myocardium (heart muscle) by implantation of external heart muscle cells is emerging as a novel paradigm for restoration of the myocardial electromechanical properties, but has been significantly hampered by the paucity of cell sources for human heart cells and by the relatively limited evidence for functional integration between grafted and host cells. The recently described human embryonic stem cell (hESC) lines may provide a possible solution for the aforementioned cell sourcing problem.

  12. Impaired mitochondrial function in chronically ischemic human heart

    DEFF Research Database (Denmark)

    Stride, Nis Ottesen; Larsen, Steen; Hey-Mogensen, Martin

    2013-01-01

    , and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared.......05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found....

  13. How Live Performance Moves the Human Heart.

    Directory of Open Access Journals (Sweden)

    Haruka Shoda

    Full Text Available We investigated how the audience member's physiological reactions differ as a function of listening context (i.e., live versus recorded music contexts. Thirty-seven audience members were assigned to one of seven pianists' performances and listened to his/her live performances of six pieces (fast and slow pieces by Bach, Schumann, and Debussy. Approximately 10 weeks after the live performance, each of the audience members returned to the same room and listened to the recorded performances of the same pianists' via speakers. We recorded the audience members' electrocardiograms in listening to the performances in both conditions, and analyzed their heart rates and the spectral features of the heart-rate variability (i.e., HF/TF, LF/HF. Results showed that the audience's heart rate was higher for the faster than the slower piece only in the live condition. As compared with the recorded condition, the audience's sympathovagal balance (LF/HF was less while their vagal nervous system (HF/TF was activated more in the live condition, which appears to suggest that sharing the ongoing musical moments with the pianist reduces the audience's physiological stress. The results are discussed in terms of the audience's superior attention and temporal entrainment to live performance.

  14. Plasma urocortin in human systolic heart failure.

    Science.gov (United States)

    Ng, Leong L; Loke, Ian W; O'Brien, Russell J; Squire, Iain B; Davies, Joan E

    2004-04-01

    Urocortin (UCN), a member of the corticotrophin-releasing factor family, is expressed in heart, brain and gut. UCN has potent cardiostimulatory, cardioprotective, vasodilator and diuretic/natriuretic effects, and cardiac UCN expression is increased in heart failure (HF). In the present study, we investigated plasma levels of UCN in 119 patients with HF and 212 age- and gender-matched controls to clarify its relationship with gender and disease severity. UCN was elevated in HF [normal males, 19.5 (3.9-68.8) pmol/l and HF males, 50.2 (6.9-108.2) pmol/l, P fall in UCN levels with increasing NYHA class was reinforced by a significant correlation between UCN and ejection fraction ( r(s) = 0.45, P < 0.0005) in HF patients. Although receiver operating characteristic (ROC) curves for diagnosis of all HF cases yielded an area under the curve (AUC) of 0.76, ROC AUCs for patients with early HF (NYHA class I and II) were better (0.91). ROC AUCs for logistic models incorporating N-terminal probrain natriuretic peptide (N-BNP) and UCN were better than either peptide alone. In conclusion, plasma UCN is elevated in HF, especially in its early stages. Its decline with increasing HF severity may expedite disease progression due to diminished cardioprotective/anti-inflammatory effects. UCN measurement may also complement N-BNP in the diagnosis of early HF.

  15. FISH CONSUMPTION, METHYLMERCURY, AND HUMAN HEART DISEASE.

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    LIPFERT, F.W.; SULLIVAN, T.M.

    2005-09-21

    Environmental mercury continues to be of concern to public health advocates, both in the U.S. and abroad, and new research continues to be published. A recent analysis of potential health benefits of reduced mercury emissions has opened a new area of public health concern: adverse effects on the cardiovascular system, which could account for the bulk of the potential economic benefits. The authors were careful to include caveats about the uncertainties of such impacts, but they cited only a fraction of the applicable health effects literature. That literature includes studies of the potentially harmful ingredient (methylmercury, MeHg) in fish, as well as of a beneficial ingredient, omega-3 fatty acids or ''fish oils''. The U.S. Food and Drug Administration (FDA) recently certified that some of these fat compounds that are primarily found in fish ''may be beneficial in reducing coronary heart disease''. This paper briefly summarizes and categorizes the extensive literature on both adverse and beneficial links between fish consumption and cardiovascular health, which are typically based on studies of selected groups of individuals (cohorts). Such studies tend to comprise the ''gold standard'' of epidemiology, but cohorts tend to exhibit a great deal of variability, in part because of the limited numbers of individuals involved and in part because of interactions with other dietary and lifestyle considerations. Note that eating fish will involve exposure to both the beneficial effects of fatty acids and the potentially harmful effects of contaminants like Hg or PCBs, all of which depend on the type of fish but tend to be correlated within a population. As a group, the cohort studies show that eating fish tends to reduce mortality, especially due to heart disease, for consumption rates up to about twice weekly, above which the benefits tend to level off. A Finnish cohort study showed increased mortality risks

  16. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    International Nuclear Information System (INIS)

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-01

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  17. Heart rate variability enhances the prognostic value of established parameters in patients with congestive heart failure.

    Science.gov (United States)

    Krüger, C; Lahm, T; Zugck, C; Kell, R; Schellberg, D; Schweizer, M W F; Kübler, W; Haass, M

    2002-12-01

    This prospective study evaluated whether heart rate variability (HRV) assessed from Holter ECG has prognostic value in addition to established parameters in patients with congestive heart failure (CHF). The study included 222 patients with CHF due to dilated or ischemic cardiomyopathy (left ventricular ejection fraction LVEF 21+/-1%; mean+/-SEM). During a mean follow-up of 15+/-1 months, 38 (17%) patients died and 45 (20%) were hospitalized due to worsening of CHF. The HRV parameter SDNN (standard deviation of all intervals between normal beats) was significantly lower in non-surviving or hospitalized than in event-free patients (118+/-6 vs 142+/-5 ms), as were LVEF (18+/-1 vs 23+/-1%), and peak oxygen uptake during exercise (peak VO(2)) (12.8+/-0.5 vs 15.6+/-0.5 ml/min/kg). While each of these parameters was a risk predictor in univariate analysis, multivariate analysis revealed that HRV provides both independent and additional prognostic information with respect to the risk 'cardiac mortality or deterioration of CHF'. It is concluded that the determination of HRV enhances the prognostic power given by the most widely used parameters LVEF and peak VO(2) in the prediction of mortality or deterioration of CHF and thus enables to improve risk stratification.

  18. hHGF overexpression in myoblast sheets enhances their angiogenic potential in rat chronic heart failure.

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    Antti Siltanen

    2011-04-01

    Full Text Available After severe myocardial infarction (MI, heart failure results from ischemia, fibrosis, and remodeling. A promising therapy to enhance cardiac function and induce therapeutic angiogenesis via a paracrine mechanism in MI is myoblast sheet transplantation. We hypothesized that in a rat model of MI-induced chronic heart failure, this therapy could be further improved by overexpression of the antiapoptotic, antifibrotic, and proangiogenic hepatocyte growth factor (HGF in the myoblast sheets. We studied the ability of wild type (L6-WT and human HGF-expressing (L6-HGF L6 myoblast sheet-derived paracrine factors to stimulate cardiomyocyte, endothelial cell, or smooth muscle cell migration in culture. Further, we studied the autocrine effect of hHGF-expression on myoblast gene expression profiles by use of microarray analysis. We induced MI in Wistar rats by left anterior descending coronary artery (LAD ligation and allowed heart failure to develop for 4 weeks. Thereafter, we administered L6-WT (n = 15 or L6-HGF (n = 16 myoblast sheet therapy. Control rats (n = 13 underwent LAD ligation and rethoracotomy without therapy, and five rats underwent a sham operation in both surgeries. We evaluated cardiac function with echocardiography at 2 and 4 weeks after therapy, and analyzed cardiac angiogenesis and left ventricular architecture from histological sections at 4 weeks. Paracrine mediators from L6-HGF myoblast sheets effectively induced migration of cardiac endothelial and smooth muscle cells but not cardiomyocytes. Microarray data revealed that hHGF-expression modulated myoblast gene expression. In vivo, L6-HGF sheet therapy effectively stimulated angiogenesis in the infarcted and non-infarcted areas. Both L6-WT and L6-HGF therapies enhanced cardiac function and inhibited remodeling in a similar fashion. In conclusion, L6-HGF therapy effectively induced angiogenesis in the chronically failing heart. Cardiac function, however, was not further

  19. Influence of heart failure on nucleolar organization and protein expression in human hearts

    International Nuclear Information System (INIS)

    Roselló-Lletí, Esther; Rivera, Miguel; Cortés, Raquel; Azorín, Inmaculada; Sirera, Rafael; Martínez-Dolz, Luis; Hove, Leif; Cinca, Juan; Lago, Francisca; González-Juanatey, José R.; Salvador, Antonio; Portolés, Manuel

    2012-01-01

    Highlights: ► Heart failure alters nucleolar morphology and organization. ► Nucleolin expression is significant increased in ischemic and dilated cardiomyopathy. ► Ventricular function of heart failure patients was related with nucleolin levels. -- Abstract: We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n = 38) and DCM (n = 27) patients, undergoing heart transplantation and control donors (n = 6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p < 0.05) and DCM (141%, p < 0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p < 0.05) and DCM (1.70-fold, p < 0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p < 0.0001), and it was increased in pathological hearts (p < 0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p < 0.05 and 131%, p < 0.001) and DCM (56%, p < 0.01 and 69%, p < 0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p < 0.001), perinucleolar chromatin (p < 0.01) and dense fibrillar components (p < 0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p < 0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein.

  20. Influence of heart failure on nucleolar organization and protein expression in human hearts

    Energy Technology Data Exchange (ETDEWEB)

    Rosello-Lleti, Esther; Rivera, Miguel; Cortes, Raquel [Cardiocirculatory Unit, Research Center, Hospital Universitario La Fe, Valencia (Spain); Azorin, Inmaculada [Experimental Neurology, Research Center, Hospital Universitario La Fe, Valencia (Spain); Sirera, Rafael [Biotechnology Department, Universidad Politecnica, Valencia (Spain); Martinez-Dolz, Luis [Cardiology Unit, Hospital Universitario La Fe, Valencia (Spain); Hove, Leif; Cinca, Juan [Cardiology Unit, Hospital San Pau, Barcelona (Spain); Lago, Francisca; Gonzalez-Juanatey, Jose R. [Cardiology Unit, Institute of Biomedical Research, Hospital Clinicode Santiagode Compostela (Spain); Salvador, Antonio [Experimental Neurology, Research Center, Hospital Universitario La Fe, Valencia (Spain); Portoles, Manuel, E-mail: portoles_man@gva.es [Cell Biology and Pathology Unit, Research Center, Hospital Universitario La Fe, Valencia (Spain)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Heart failure alters nucleolar morphology and organization. Black-Right-Pointing-Pointer Nucleolin expression is significant increased in ischemic and dilated cardiomyopathy. Black-Right-Pointing-Pointer Ventricular function of heart failure patients was related with nucleolin levels. -- Abstract: We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n = 38) and DCM (n = 27) patients, undergoing heart transplantation and control donors (n = 6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p < 0.05) and DCM (141%, p < 0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p < 0.05) and DCM (1.70-fold, p < 0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p < 0.0001), and it was increased in pathological hearts (p < 0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p < 0.05 and 131%, p < 0.001) and DCM (56%, p < 0.01 and 69%, p < 0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p < 0.001), perinucleolar chromatin (p < 0.01) and dense fibrillar components (p < 0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p < 0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein.

  1. Heart research advances using database search engines, Human Protein Atlas and the Sydney Heart Bank.

    Science.gov (United States)

    Li, Amy; Estigoy, Colleen; Raftery, Mark; Cameron, Darryl; Odeberg, Jacob; Pontén, Fredrik; Lal, Sean; Dos Remedios, Cristobal G

    2013-10-01

    This Methodological Review is intended as a guide for research students who may have just discovered a human "novel" cardiac protein, but it may also help hard-pressed reviewers of journal submissions on a "novel" protein reported in an animal model of human heart failure. Whether you are an expert or not, you may know little or nothing about this particular protein of interest. In this review we provide a strategic guide on how to proceed. We ask: How do you discover what has been published (even in an abstract or research report) about this protein? Everyone knows how to undertake literature searches using PubMed and Medline but these are usually encyclopaedic, often producing long lists of papers, most of which are either irrelevant or only vaguely relevant to your query. Relatively few will be aware of more advanced search engines such as Google Scholar and even fewer will know about Quertle. Next, we provide a strategy for discovering if your "novel" protein is expressed in the normal, healthy human heart, and if it is, we show you how to investigate its subcellular location. This can usually be achieved by visiting the website "Human Protein Atlas" without doing a single experiment. Finally, we provide a pathway to discovering if your protein of interest changes its expression level with heart failure/disease or with ageing. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  2. Stem cell markers in the heart of the human newborn

    Directory of Open Access Journals (Sweden)

    Armando Faa

    2016-07-01

    Full Text Available The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. Several recent studies now show that the different cell types that characterize the adult human heart arise from a common ancestor. Human cardiac stem cells differentiate into cardiomyocytes, and, in lesser extent, into smooth muscle and endothelial cells. The characterization of human cardiac stem cells (CSCs has important clinical implications. In recent years, CD117 (c-kit has been reported to mark a subtype of stem/progenitor cells in the human heart, with stem cell-like properties, including the ability to self-renewal and clonogenicity multipotentiality. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  3. Fractionated magnetic-resonance elastography on the human heart

    International Nuclear Information System (INIS)

    Rump, Jens

    2008-01-01

    Imaging techniques, including magnetic resonance imaging, belong to the most important tools in modern medical diagnostics. Another diagnostic aid is palpation, which is suitable for the qualitative characterization of pathological changes in organs near the surface. Magnetic resonance elastography (MRE) is a combination of these techniques. In principle, MRE uses motionsensitive MR-imaging to depict tissue deformation caused by externally induced shear waves. The type of deformation supply useful information about the elasticity of the tissue. Cardiac disorders are among the most common diseases. The goal of this study was to develop a method of applying in-vivo MRE to the human heart. The development of the mechanical stimulus, ultimately resulting in the introduction of an audio speaker as the source of vibration, provided the necessary means to introduce vibrations into inner organs. A crucial factor in applying MRE to the heart is the speed of the recording, which led to the development of ''fractional MRE''. The currently conventional fast heart imaging techniques were used as a starting point. The use of an unbalanced phase preparation gradient in the balanced steady-state imaging technique resulted in an improved phase-to-noise ratio. Along with the spoiled steady-state MRE imaging technique, initial MRE-studies on the human heart were performed. For the first time, externally induced mechanical vibrations were successfully introduced into the heart and were detected using fractional MRE with a high temporal resolution. The modulation of the shear wave amplitudes observed in the myocard of 6 healthy subjects correlated with the phases of the cardiac cycle. The techniques and methods developed here are a step toward routine clinical application of MRE of the heart and indicate high potential in the area of early diagnosis of cardiac disease. (orig.)

  4. General anesthesia suppresses normal heart rate variability in humans

    Science.gov (United States)

    Matchett, Gerald; Wood, Philip

    2014-06-01

    The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

  5. The human heart: application of the golden ratio and angle.

    Science.gov (United States)

    Henein, Michael Y; Zhao, Ying; Nicoll, Rachel; Sun, Lin; Khir, Ashraf W; Franklin, Karl; Lindqvist, Per

    2011-08-04

    The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. A new look at the comparative physiology of insect and human hearts.

    Science.gov (United States)

    Sláma, Karel

    2012-08-01

    Recent electrocardiographic (ECG) studies of insect hearts revealed the presence of human-like, involuntary and purely myogenic hearts. Certain insects, like a small light-weight species of hoverfly (Episyrphus balteatus), have evolved a very efficient cardiac system comprised of a compact heart ventricle and a narrow tube of aorta, which evolved as an adaptation to sustained hovering flights. Application of thermocardiographic and optocardiographic ECG methods revealed that adult flies of this species use the compact muscular heart chamber (heart ventricle) for intensive pumping of insect "blood" (haemolymph) into the head and thorax which is ringed all over with indirect flight musculature. The recordings of these hearts revealed extremely high, record rates of forward-directed, anterograde heartbeat (up to 10Hz), associated with extremely enhanced synchronic (not peristaltic) propagation of systolic myocardial contractions (32.2mm/s at room temperature). The relatively slow, backward-directed or retrograde cardiac contractions occurred only sporadically in the form of individual or twinned pulses replacing occasionally the resting periods. The compact heart ventricle contained bi-directional lateral apertures, whose opening and closure diverted the intracardiac anterograde "blood" streams between the abdominal haemocoelic cavity and the aortan artery, respectively. The visceral organs of this flying machine (crop, midgut) exhibited myogenic, extracardiac peristaltic pulsations similar to heartbeat, including the periodically reversed forward and backward direction of the peristaltic waves. The tubular crop contracted with a periodicity of 1Hz, both forwards and backwards, with propagation of the peristaltic waves at 4.4mm/s. The air-inflated and blindly ended midgut contracted at 0.2Hz, with a 0.9mm/s propagation of the peristaltic contraction waves. The neurogenic system of extracardiac haemocoelic pulsations, widely engaged in the regulation of circulatory and

  7. Moderate eugenics and human enhancement.

    Science.gov (United States)

    Selgelid, Michael J

    2014-02-01

    Though the reputation of eugenics has been tarnished by history, eugenics per se is not necessarily a bad thing. Many advocate a liberal new eugenics--where individuals are free to choose whether or not to employ genetic technologies for reproductive purposes. Though genetic interventions aimed at the prevention of severe genetic disorders may be morally and socially acceptable, reproductive liberty in the context of enhancement may conflict with equality. Enhancement could also have adverse effects on utility. The enhancement debate requires a shift in focus. What the equality and/or utility costs of enhancement will be is an empirical question. Rather than philosophical speculation, more social science research is needed to address it. Philosophers, meanwhile, should address head-on the question of how to strike a balance between liberty, equality, and utility in cases of conflict (in the context of genetics).

  8. Human Enhancement and the Story of Job.

    Science.gov (United States)

    Agar, Nicholas; McDonald, Johnny

    2017-07-01

    This article explores some implications of the concept of transformative change for the debate about human enhancement. A transformative change is understood to be one that significantly alters the value an individual places on his or her experiences or achievements. The clearest examples of transformative change come from science fiction, but the concept can be illuminatingly applied to the enhancement debate. We argue that it helps to expose a threat from too much enhancement to many of the things that make human lives valuable. Among the things threated by enhancement are our relationships with other human beings. The potential to lose these relationships provides a compelling reason for almost all humans to reject too much enhancement.

  9. Angiotensinergic and noradrenergic neurons in the rat and human heart.

    Science.gov (United States)

    Patil, Jaspal; Stucki, Silvan; Nussberger, Juerg; Schaffner, Thomas; Gygax, Susanne; Bohlender, Juergen; Imboden, Hans

    2011-02-25

    Although the physiological and pharmacological evidences suggest a role for angiotensin II (Ang II) with the mammalian heart, the source and precise location of Ang II are unknown. To visualize and quantitate Ang II in atria, ventricular walls and interventricular septum of the rat and human heart and to explore the feasibility of local Ang II production and function, we investigated by different methods the expression of proteins involved in the generation and function of Ang II. We found mRNA of angiotensinogen (Ang-N), of angiotensin converting enzyme, of the angiotensin type receptors AT(1A) and AT₂ (AT(1B) not detected) as well as of cathepsin D in any part of the hearts. No renin mRNA was traceable. Ang-N mRNA was visualized by in situ hybridization in atrial ganglial neurons. Ang II and dopamine-β-hydroxylase (DβH) were either colocalized inside the same neuronal cell or the neurons were specialized for Ang II or DβH. Within these neurons, the vesicular acetylcholine transporter (VAChT) was neither colocalized with Ang II nor DβH, but VAChT-staining was found with synapses en passant encircle these neuronal cells. The fibers containing Ang II exhibited with blood vessels and with cardiomyocytes supposedly angiotensinergic synapses en passant. In rat heart, right atrial median Ang II concentration appeared higher than septal and ventricular Ang II. The distinct colocalization of neuronal Ang II with DβH in the heart may indicate that Ang II participates together with norepinephrine in the regulation of cardiac functions: produced as a cardiac neurotransmitter Ang II may have inotropic, chronotropic or dromotropic effects in atria and ventricles and contributes to blood pressure regulation. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Human heart disease : lessons from human pluripotent stem cell-derived cardiomyocytes

    NARCIS (Netherlands)

    Giacomelli, E.; Mummery, C.L.; Bellin, M.

    2017-01-01

    Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current

  11. The world's first human-to-human heart transplant at Groote Schuur ...

    African Journals Online (AJOL)

    The world's first human-to-human heart transplant at Groote Schuur Hospital: 50 years later. Johan Brink, Tim Pennel, Karen Seele, Peter Zilla. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO ...

  12. DENdb: database of integrated human enhancers

    KAUST Repository

    Ashoor, Haitham

    2015-09-05

    Enhancers are cis-acting DNA regulatory regions that play a key role in distal control of transcriptional activities. Identification of enhancers, coupled with a comprehensive functional analysis of their properties, could improve our understanding of complex gene transcription mechanisms and gene regulation processes in general. We developed DENdb, a centralized on-line repository of predicted enhancers derived from multiple human cell-lines. DENdb integrates enhancers predicted by five different methods generating an enriched catalogue of putative enhancers for each of the analysed cell-lines. DENdb provides information about the overlap of enhancers with DNase I hypersensitive regions, ChIP-seq regions of a number of transcription factors and transcription factor binding motifs, means to explore enhancer interactions with DNA using several chromatin interaction assays and enhancer neighbouring genes. DENdb is designed as a relational database that facilitates fast and efficient searching, browsing and visualization of information.

  13. DENdb: database of integrated human enhancers

    KAUST Repository

    Ashoor, Haitham; Kleftogiannis, Dimitrios A.; Radovanovic, Aleksandar; Bajic, Vladimir B.

    2015-01-01

    Enhancers are cis-acting DNA regulatory regions that play a key role in distal control of transcriptional activities. Identification of enhancers, coupled with a comprehensive functional analysis of their properties, could improve our understanding of complex gene transcription mechanisms and gene regulation processes in general. We developed DENdb, a centralized on-line repository of predicted enhancers derived from multiple human cell-lines. DENdb integrates enhancers predicted by five different methods generating an enriched catalogue of putative enhancers for each of the analysed cell-lines. DENdb provides information about the overlap of enhancers with DNase I hypersensitive regions, ChIP-seq regions of a number of transcription factors and transcription factor binding motifs, means to explore enhancer interactions with DNA using several chromatin interaction assays and enhancer neighbouring genes. DENdb is designed as a relational database that facilitates fast and efficient searching, browsing and visualization of information.

  14. THERP and HEART integrated methodology for human error assessment

    Science.gov (United States)

    Castiglia, Francesco; Giardina, Mariarosa; Tomarchio, Elio

    2015-11-01

    THERP and HEART integrated methodology is proposed to investigate accident scenarios that involve operator errors during high-dose-rate (HDR) treatments. The new approach has been modified on the basis of fuzzy set concept with the aim of prioritizing an exhaustive list of erroneous tasks that can lead to patient radiological overexposures. The results allow for the identification of human errors that are necessary to achieve a better understanding of health hazards in the radiotherapy treatment process, so that it can be properly monitored and appropriately managed.

  15. Towards a Moderate Stance on Human Enhancement

    Directory of Open Access Journals (Sweden)

    Nikil Mukerji

    2014-05-01

    Full Text Available In this essay, we argue against radical ethical views about human enhancement that either dismiss or endorse it tout court. Instead, we advocate the moderate stance that issues of enhancement should be examined with an open mind and on a case-by-case basis. To make this view plausible, we offer three reasons. The first lies in the fact that it is difficult to delineate enhancement conceptually, which makes it hard to argue for general ethical conclusions about it. The second is that an appropriate view of the edifice of moral theory suggests that tenable moral judgements about human enhancement are the result of a careful consideration of the pros and cons that attach to the use of a specific enhancement technology. Lastly, we show that important normative factors in the enhancement debate can be used both in arguments for and in arguments against enhancement. The bottom line of our discussion is that we should treat issues of human enhancement like we do any other ethical issue, viz. by weighing up the reasons pro and con.

  16. Muscle metaboreflex and autonomic regulation of heart rate in humans

    DEFF Research Database (Denmark)

    Fisher, James P; Adlan, Ahmed M; Shantsila, Alena

    2013-01-01

    ) conditions, but attenuated with β-adrenergic blockade (0.2 ± 1 beats min(-1); P > 0.05 vs. rest). Thus muscle metaboreflex activation-mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg......We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi-lateral thigh cuff inflation) during leg cycling...... exercise, (2) isolated muscle metaboreflex activation (post-exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), β1-adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR...

  17. Simulation and mechanistic investigation of the arrhythmogenic role of the late sodium current in human heart failure.

    Directory of Open Access Journals (Sweden)

    Beatriz Trenor

    Full Text Available Heart failure constitutes a major public health problem worldwide. The electrophysiological remodeling of failing hearts sets the stage for malignant arrhythmias, in which the role of the late Na(+ current (I(NaL is relevant and is currently under investigation. In this study we examined the role of I(NaL in the electrophysiological phenotype of ventricular myocytes, and its proarrhythmic effects in the failing heart. A model for cellular heart failure was proposed using a modified version of Grandi et al. model for human ventricular action potential that incorporates the formulation of I(NaL. A sensitivity analysis of the model was performed and simulations of the pathological electrical activity of the cell were conducted. The proposed model for the human I(NaL and the electrophysiological remodeling of myocytes from failing hearts accurately reproduce experimental observations. The sensitivity analysis of the modulation of electrophysiological parameters of myocytes from failing hearts due to ion channels remodeling, revealed a role for I(NaL in the prolongation of action potential duration (APD, triangulation of the shape of the AP, and changes in Ca(2+ transient. A mechanistic investigation of intracellular Na(+ accumulation and APD shortening with increasing frequency of stimulation of failing myocytes revealed a role for the Na(+/K(+ pump, the Na(+/Ca(2+ exchanger and I(NaL. The results of the simulations also showed that in failing myocytes, the enhancement of I(NaL increased the reverse rate-dependent APD prolongation and the probability of initiating early afterdepolarizations. The electrophysiological remodeling of failing hearts and especially the enhancement of the I(NaL prolong APD and alter Ca(2+ transient facilitating the development of early afterdepolarizations. An enhanced I(NaL appears to be an important contributor to the electrophysiological phenotype and to the dysregulation of [Ca(2+](i homeostasis of failing myocytes.

  18. Defining the molecular signatures of human right heart failure.

    Science.gov (United States)

    Williams, Jordan L; Cavus, Omer; Loccoh, Emefah C; Adelman, Sara; Daugherty, John C; Smith, Sakima A; Canan, Benjamin; Janssen, Paul M L; Koenig, Sara; Kline, Crystal F; Mohler, Peter J; Bradley, Elisa A

    2018-03-01

    Right ventricular failure (RVF) varies significantly from the more common left ventricular failure (LVF). This study was undertaken to determine potential molecular pathways that are important in human right ventricular (RV) function and may mediate RVF. We analyzed mRNA of human non-failing LV and RV samples and RVF samples from patients with pulmonary arterial hypertension (PAH), and post-LVAD implantation. We then performed transcript analysis to determine differential expression of genes in the human heart samples. Immunoblot quantification was performed followed by analysis of non-failing and failing phenotypes. Inflammatory pathways were more commonly dysregulated in RV tissue (both non-failing and failing phenotypes). In non-failing human RV tissue we found important differences in expression of FIGF, TRAPPAC, and CTGF suggesting that regulation of normal RV and LV function are not the same. In failing RV tissue, FBN2, CTGF, SMOC2, and TRAPP6AC were differentially expressed, and are potential targets for further study. This work provides some of the first analyses of the molecular heterogeneity between human RV and LV tissue, as well as key differences in human disease (RVF secondary to pulmonary hypertension and LVAD mediated RVF). Our transcriptional data indicated that inflammatory pathways may be more important in RV tissue, and changes in FIGF and CTGF supported this hypothesis. In PAH RV failure samples, upregulation of FBN2 and CTGF further reinforced the potential significance that altered remodeling and inflammation play in normal RV function and failure. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Magnetic resonance (MR) cine imaging of the human heart

    International Nuclear Information System (INIS)

    Waterton, J.C.

    1985-01-01

    A novel approach has been developed for MR cine imaging of the human heart by a modified ECG-gated 2DFT method. A pulse sequence has been devised to minimise the effects of saturation which can be anticipated in sequences that require rapid pulsing. Five frames are produced at the same anatomical level at predetermined intervals during the cardiac cycle. The total time taken to achieve this data is 8 minutes. Additional frames can be interleaved by repeating the sequence with an ECG-gated delay. The anatomical sections, which can be in any orthogonal plane, are then displayed as a cine loop. Cine display in the coronal plane has been used to examine 10 volunteers and 12 patients. In addition to the morphological feature displayed in single slice ECG-gated imaging, areas of dyskinesia can be detected and subjective estimates have been made of left ventricular function. (author)

  20. Stakeholder Capability Enhancement as a Path to Promote Human Dignity and Cooperative Advantage

    NARCIS (Netherlands)

    Westermann-Behaylo, M.K.; Van Buren III, H.J.; Berman, S.L.

    2016-01-01

    Promoting dignity is at the heart of the human capability approach to development. We introduce the concept of stakeholder capability enhancement, beginning with a discussion of the capability approach to development proposed by Sen (1985) and further advanced by Nussbaum (1990) to incorporate

  1. Patentability of methods of human enhancement

    DEFF Research Database (Denmark)

    Nordberg, Ana

    2015-01-01

    This article explores how to apply patentability rules to human enhancement, particularly focusing on Article 53(c) of the European Patent Convention (EPC). The global size and value of the cosmetic and wellness market and industry allow for the prediction of considerable market potential for hum...... future evolution and the corresponding public policy choices. This article seeks to provide prospective patentees with guidance and awareness concerning the patentability of methods for human enhancement.......This article explores how to apply patentability rules to human enhancement, particularly focusing on Article 53(c) of the European Patent Convention (EPC). The global size and value of the cosmetic and wellness market and industry allow for the prediction of considerable market potential for human...... enhancement. Patents will be instrumental for companies to protect investment in innovation and tap into this potentially valuable market. The European patent system contains, in Article 53(c) EPC, an exception from patentability for methods for treatment and diagnostic methods. Such rule was created...

  2. Love troubles : human attachment and biomedical enhancements

    NARCIS (Netherlands)

    Nyholm, S.

    ABSTRACT In fascinating recent work, Julian Savulescu and his various co-authors argue that human love is one of the things we can improve upon using biomedical enhancements. Is that so? This article first notes that Savulescu and his co-authors mainly treat love as a means to various other goods.

  3. Human Capital Development Policies: Enhancing Employees Satisfaction

    Science.gov (United States)

    Wan, Hooi Lan

    2007-01-01

    Purpose--The aim of this article is to gain insight into some of the human capital development (HCD) policies that enhance employee satisfaction. A salient focus of the study is to assess whether employees in globalised foreign-owned MNCs are likely to be more satisfied with the HCD policies than with the practices employed by locally owned MNCs.…

  4. Epicardial excitation pattern as observed in the isolated revived and perfused fetal human heart

    NARCIS (Netherlands)

    Durrer, D.; Büller, J.; Graaff, P.; Lo, G.I.; Meijler, F.L.

    1961-01-01

    The resuscitated fetal human heart can be used as an experimental tooI for the investigation of the excitatory process in the human heart. During perfusion the configuration of the epicardial electrocardiograms does not change appreciably. For accurate recording permitting a detailed analysis, the

  5. Assessment of the coronary venous system in heart failure patients by blood pool agent enhanced whole-heart MRI

    Energy Technology Data Exchange (ETDEWEB)

    Manzke, Robert [University Hospital of Ulm, Department of Internal Medicine II, Ulm (Germany); Philips Research Europe, Clinical Sites Research, Hamburg (Germany); Binner, Ludwig; Bornstedt, Axel; Merkle, Nico; Lutz, Anja; Gradinger, Robert [University Hospital of Ulm, Department of Internal Medicine II, Ulm (Germany); Rasche, Volker [University Hospital of Ulm, Department of Internal Medicine II, Ulm (Germany); Experimental Cardiovascular Imaging, Internal Medicine II, Ulm (Germany)

    2011-04-15

    To investigate the feasibility of MRI for non-invasive assessment of the coronary sinus (CS) and the number and course of its major tributaries in heart failure patients. Fourteen non-ischaemic heart failure patients scheduled for cardiac resynchronisation therapy (CRT) underwent additional whole-heart coronary venography. MRI was performed 1 day before device implantation. The visibility, location and dimensions of the CS and its major tributaries were assessed and the number of potential implantation sites identified. The MRI results were validated by X-ray venography conventionally acquired during the device implantation procedure. The right atrium (RA), CS and mid-cardiac vein (MCV) could be visualised in all patients. 36% of the identified candidate branches were located posterolaterally, 48% laterally and 16% anterolaterally. The average diameter of the CS was quantified as 9.8 mm, the posterior interventricular vein (PIV) 4.6 mm, posterolateral segments 3.3 mm, lateral 2.9 mm and anterolateral 2.9 mm. Concordance with X-ray in terms of number and location of candidate branches was given in most cases. Contrast-enhanced MRI venography appears feasible for non-invasive pre-interventional assessment of the course of the CS and its major tributaries. (orig.)

  6. Assessment of the coronary venous system in heart failure patients by blood pool agent enhanced whole-heart MRI

    International Nuclear Information System (INIS)

    Manzke, Robert; Binner, Ludwig; Bornstedt, Axel; Merkle, Nico; Lutz, Anja; Gradinger, Robert; Rasche, Volker

    2011-01-01

    To investigate the feasibility of MRI for non-invasive assessment of the coronary sinus (CS) and the number and course of its major tributaries in heart failure patients. Fourteen non-ischaemic heart failure patients scheduled for cardiac resynchronisation therapy (CRT) underwent additional whole-heart coronary venography. MRI was performed 1 day before device implantation. The visibility, location and dimensions of the CS and its major tributaries were assessed and the number of potential implantation sites identified. The MRI results were validated by X-ray venography conventionally acquired during the device implantation procedure. The right atrium (RA), CS and mid-cardiac vein (MCV) could be visualised in all patients. 36% of the identified candidate branches were located posterolaterally, 48% laterally and 16% anterolaterally. The average diameter of the CS was quantified as 9.8 mm, the posterior interventricular vein (PIV) 4.6 mm, posterolateral segments 3.3 mm, lateral 2.9 mm and anterolateral 2.9 mm. Concordance with X-ray in terms of number and location of candidate branches was given in most cases. Contrast-enhanced MRI venography appears feasible for non-invasive pre-interventional assessment of the course of the CS and its major tributaries. (orig.)

  7. Proton nuclear magnetic resonance imaging of regionally ischemic canine hearts: effects of paramagnetic proton signal enhancement

    International Nuclear Information System (INIS)

    Brady, T.J.; Goldman, M.R.; Pykett, I.L.; Buonanno, F.S.; Kistler, J.P.; Newhouse, J.H.; Burt, C.T.; Hinshaw, W.S.; Pohost, G.M.

    1982-01-01

    In a study to evaluate the potential of proton nuclear magnetic resonance (NMR) imaging with and without manganese contrast enhancement for detecting acute myocardial infarction, 12 dogs underwent 90-minute occlusion of the left circumflex coronary artery. Transverse-section NMR images of the excised, nonbeating heart were obtained at 1-cm intervals using the steady-state-free-precession (SSFP) technique. All NMR images revealed detailed structure of the heart. The three hearts without manganese showed no difference in intensity between the normal and the ischemic posterior regions, whereas those with manganese demonstrated a clearly demarcated zone of reduced signal intensity consistent with the ischemic zone. It is concluded that high-resolution tomograms of the excised canine myocardium can be obtained using proton NMR imaging. With the SSFP imaging technique, proton signal enhancement with manganese infusion is necessary to differentiate between ischemic and nonischemic myocardium after 90 minutes of coronary occlusion

  8. In Defense of Pharmaceutically Enhancing Human Morality.

    Science.gov (United States)

    Protopapadakis, Evangelos D

    2017-01-01

    I will discuss the prospect of pharmaceutically enhancing human morality and decision making in such a way as to eliminate morally unjustifiable choices and promote desirable ones. Our species in the relatively short period since it has emerged has enormously advanced in knowledge, science, and technical progress. When it comes to moral development, the distance it has covered is almost negligible. What if we could medically accelerate our moral development? What if we could once and for all render our species totally immune to certain vices? I will examine whether pharmaceutically intervening in human morality would compromise the autonomy of moral agents. I will argue that the argument from the autonomy of the moral agent is neither stable nor convincing. In the light of Kantian ethics we might consider moral enhancement by pharmaceutical means to be a perfect duty for moral agents.

  9. Heart Rate Variability (HRV biofeedback: A new training approach for operator’s performance enhancement

    Directory of Open Access Journals (Sweden)

    Auditya Purwandini Sutarto

    2010-06-01

    Full Text Available The widespread implementation of advanced and complex systems requires predominantly operators’ cognitive functions and less importance of human manual control. On the other hand, most operators perform their cognitive functions below their peak cognitive capacity level due to fatigue, stress, and boredom. Thus, there is a need to improve their cognitive functions during work. The goal of this paper is to present a psychophysiology training approach derived from cardiovascular response named heart rate variability (HRV biofeedback. Description of resonant frequency biofeedback - a specific HRV training protocol - is discussed as well as its supported researches for the performance enhancement. HRV biofeedback training works by teaching people to recognize their involuntary HRV and to control patterns of this physiological response. The training is directed to increase HRV amplitude that promotes autonomic nervous system balance. This balance is associated with improved physiological functioning as well as psychological benefits. Most individuals can learn HRV biofeedback training easily which involves slowing the breathing rate (around six breaths/min to each individual’s resonant frequency at which the amplitude of HRV is maximized. Maximal control over HRV can be obtained in most people after approximately four sessions of training. Recent studies have demonstrated the effectiveness of HRV biofeedback to the improvement of some cognitive functions in both simulated and real industrial operators.

  10. Characteristic parameters of electromagnetic signals from a human heart system

    International Nuclear Information System (INIS)

    Liu Xin-Yuan; Wang Yin; Zhang Su-Ming; Gao Hong-Lei; Pei Liu-Qing; Dai Yuan-Dong

    2011-01-01

    The electromagnetic field of a human heart system is a bioelectromagnetic field. Electrocardiography (ECG) and magnetocardiography (MCG) are both carriers of electromagnetic information about the cardiac system, and they are nonstationary signals. In this study, ECG and MCG data from healthy subjects are acquired; the MCG data are captured using a high-T c radio frequency superconducting quantum interference device (HTc rf SQUIDs) and the QRS complexes in these data are analysed by the evolutionary spectrum analysis method. The results show that the quality factor Q and the central frequency f z of the QRS complex evolutionary spectrum are the characteristic parameters (CHPs) of ECG and MCG in the time—frequency domain. The confidence intervals of the mean values of the CHPs are estimated by the Student t distribution method in mathematical statistics. We believe that there are threshold ranges of the mean values of Q and f z for healthy subjects. We have postulated the following criterion: if the mean values of CHPs are in the proper ranges, the cardiac system is in a normal condition and it possesses the capability of homeostasis. In contrast, if the mean values of the CHPs do not lie in the proper ranges, the homeostasis of the cardiac system is lacking and some cardiac disease may follow. The results and procedure of MCG CHPs in the study afford a technological route for the application of HTc rf SQUIDs in cardiology. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  11. Resonance of about-weekly human heart rate rhythm with solar activity change.

    Science.gov (United States)

    Cornelissen, G; Halberg, F; Wendt, H W; Bingham, C; Sothern, R B; Haus, E; Kleitman, E; Kleitman, N; Revilla, M A; Revilla, M; Breus, T K; Pimenov, K; Grigoriev, A E; Mitish, M D; Yatsyk, G V; Syutkina, E V

    1996-12-01

    In several human adults, certain solar activity rhythms may influence an about 7-day rhythm in heart rate. When no about-weekly feature was found in the rate of change in sunspot area, a measure of solar activity, the double amplitude of a circadian heart rate rhythm, approximated by the fit of a 7-day cosine curve, was lower, as was heart rate corresponds to about-weekly features in solar activity and/or relates to a sunspot cycle.

  12. The human factor: enhancing women's rights.

    Science.gov (United States)

    Steinzor, N

    1995-01-01

    The Universal Declaration of Human Rights, adopted by the UN in 1948, declares that all human beings are born free and equal in dignity and rights, and that everyone has the right to life, liberty, and security of person. In practice, however, far from everyone has these rights, especially women. Many women worldwide have neither the awareness of nor access to family planning methods with which they could regulate their fertility and childbearing. Thus deprived of their reproductive freedom, these women cannot pursue education, employment, and other life options which would otherwise be readily available to them were they not saddled with poor reproductive health and too many children. Expanded choices enhance the status of women, which in turn helps them to reduce fertility rates and stabilize population growth. The author discusses how the wide range of cultural and social norms, and economic and political systems worldwide make it very difficult and complex to actually implement universal human rights.

  13. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    International Nuclear Information System (INIS)

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalén; Palmqvist, Lars; Jeppsson, Anders; Hultén, Lillemor Mattsson

    2012-01-01

    Highlights: ► We found a 17-fold upregulation of ALOX15 in the ischemic heart. ► Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. ► We observed increased levels of proinflammatory markers in ischemic heart tissue. ► Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1α (HIF-1α) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1α mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield important insights into the underlying association between hypoxia and inflammation in the human ischemic heart disease.

  14. Reconstructed image of human heart for total artificial heart implantation, based on MR image and cast silicone model of heart

    International Nuclear Information System (INIS)

    Komoda, Takashi; Maeta, Hajime; Uyama, Chikao.

    1991-01-01

    Based on transverse (TRN) and LV long axis (LAX) MR images of two cadaver hearts, three-dimensional (3-D) computer models of the connecting interface between remaining heart and total artificial heart, i.e., mitral and tricuspid valvular annuli (MVA and TVA), ascending aorta (Ao) and pulmonary artery (PA), were reconstructed to compare the shape and the size of MVA and those of TVA, the distance between the center of MVA and TVA (D G ), the angle between the plane of MVA and that of TVA (R T ), and the angles of Ao and PA, respectively, to the plane of MVA (R A , R P ), with those obtained in cast silicone models. It was found that based on LAX rather than TRN MR image, MVA and TVA might be more precisely reconstructed. The data obtained in 3-D images of MVA, TVA, Ao and PA based on silicone models of 32 hearts were as follows: D G (cm): 4.17±0.43, R T (degrees): 22.1±11.3, R A (degrees): 54.9±15.3, R P (degrees): 30.8±17.1. (author)

  15. The Visible Heart® project and free-access website 'Atlas of Human Cardiac Anatomy'.

    Science.gov (United States)

    Iaizzo, Paul A

    2016-12-01

    Pre- and post-evaluations of implantable cardiac devices require innovative and critical testing in all phases of the design process. The Visible Heart ® Project was successfully launched in 1997 and 3 years later the Atlas of Human Cardiac Anatomy website was online. The Visible Heart ® methodologies and Atlas website can be used to better understand human cardiac anatomy, disease states and/or to improve cardiac device design throughout the development process. To date, Visible ® Heart methodologies have been used to reanimate 75 human hearts, all considered non-viable for transplantation. The Atlas is a unique free-access website featuring novel images of functional and fixed human cardiac anatomies from >400 human heart specimens. Furthermore, this website includes education tutorials on anatomy, physiology, congenital heart disease and various imaging modalities. For instance, the Device Tutorial provides examples of commonly deployed devices that were present at the time of in vitro reanimation or were subsequently delivered, including: leads, catheters, valves, annuloplasty rings, leadless pacemakers and stents. Another section of the website displays 3D models of vasculature, blood volumes, and/or tissue volumes reconstructed from computed tomography (CT) and magnetic resonance images (MRI) of various heart specimens. A new section allows the user to interact with various heart models. Visible Heart ® methodologies have enabled our laboratory to reanimate 75 human hearts and visualize functional cardiac anatomies and device/tissue interfaces. The website freely shares all images, video clips and CT/MRI DICOM files in honour of the generous gifts received from donors and their families. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

  16. Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts

    NARCIS (Netherlands)

    Vermeulen, J. T.; McGuire, M. A.; Opthof, T.; Coronel, R.; de Bakker, J. M.; Klöpping, C.; Janse, M. J.

    1994-01-01

    The aim of the study was to assess the occurrence of triggered activity and automaticity in ventricular trabeculae from failing human hearts and normal and failing rabbit hearts during exposure to a normal and altered extracellular environment. Ventricular trabeculae were harvested from failing

  17. Genomic features of human limb specific enhancers.

    Science.gov (United States)

    Ali, Shahid; Amina, Bibi; Anwar, Saneela; Minhas, Rashid; Parveen, Nazia; Nawaz, Uzma; Azam, Syed Sikandar; Abbasi, Amir Ali

    2016-10-01

    To elucidate important cellular and molecular interactions that regulate patterning and skeletal development, vertebrate limbs served as a model organ. A growing body of evidence from detailed studies on a subset of limb regulators like the HOXD cluster or SHH, reveals the importance of enhancers in limb related developmental and disease processes. Exploiting the recent genome-wide availability of functionally confirmed enhancer dataset, this study establishes regulatory interactions for dozens of human limb developmental genes. From these data, it appears that the long-range regulatory interactions are fairly common during limb development. This observation highlights the significance of chromosomal breaks/translocations in human limb deformities. Transcriptional factor (TF) analysis predicts that the differentiation of early nascent limb-bud into future territories entail distinct TF interaction networks. Conclusively, an important motivation for annotating the human limb specific regulatory networks is to pave way for the systematic exploration of their role in disease and evolution. Copyright © 2016. Published by Elsevier Inc.

  18. Preliminary study of single contrast enhanced dual energy heart imaging using dual-source CT

    International Nuclear Information System (INIS)

    Peng Jin; Zhang Longjiang; Zhou Changsheng; Lu Guangming; Ma Yan; Gu Haifeng

    2009-01-01

    Objective: To evaluate the feasibility and preliminary applications of single contrast enhanced dual energy heart imaging using dual-source CT (DSCT). Methods: Thirty patients underwent dual energy heart imaging with DSCT, of which 6 cases underwent SPECT or DSA within one week. Two experienced radiologists assessed image quality of coronary arteries and iodine map of myocardium. and correlated the coronary artery stenosis with the perfusion distribution of iodine map. Results: l00% (300/300) segments reached diagnostic standards. The mean score of image for all patients was 4.68±0.57. Mural coronary artery was present in 10 segments in S cases, atherosclerotic plaques in 32 segments in 12 cases, of which 20 segments having ≥50% stenosis, 12 segments ≤50% stenosis; dual energy CT coronary angiography was consistent with the DSA in 3 patients. 37 segmental perfusion abnormalities on iodine map were found in 15 cases, including 28 coronary blood supply segment narrow segment and 9 no coronary stenosis (including three negative segments in SPECD. Conclusion: Single contrast enhanced dual energy heart imaging can provide good coronary artery and myocardium perfusion images in the patients with appropriate heart rate, which has a potential to be used in the clinic and further studies are needed. (authors)

  19. The better human, the better than human: Limits of enhancement

    Directory of Open Access Journals (Sweden)

    Krstić Predrag

    2012-01-01

    Full Text Available Using the representations of science, fiction and science fiction, this article attempts to sketch out a certain line of development in the history of representation of the enhanced human. First it was thought that chemicals could temporarily or permanently improve his natural abilities, then artificial substitutes, inserts and accessories dominated the vision of his improvement. The most recent possibility announced is the fundamental morphological transformation of his biological composition into a completely unrecognizable, amorphous “entity” capable of taking any form. This trajectory of “improvement” of human capacities could be regarded as a gradual advancement in the realization of the pledge of traditional humanism: that man is special precisely for being able to become anything he chooses. [Projekat Ministarstva nauke Republike Srbije, br. 41004: Retke bolesti: molekularna patofiziologija, dijagnostički i terapijski modaliteti i socijalni, etički i pravni aspekti

  20. Technology-enhanced human interaction in psychotherapy.

    Science.gov (United States)

    Imel, Zac E; Caperton, Derek D; Tanana, Michael; Atkins, David C

    2017-07-01

    Psychotherapy is on the verge of a technology-inspired revolution. The concurrent maturation of communication, signal processing, and machine learning technologies begs an earnest look at how these technologies may be used to improve the quality of psychotherapy. Here, we discuss 3 research domains where technology is likely to have a significant impact: (1) mechanism and process, (2) training and feedback, and (3) technology-mediated treatment modalities. For each domain, we describe current and forthcoming examples of how new technologies may change established applications. Moreover, for each domain we present research questions that touch on theoretical, systemic, and implementation issues. Ultimately, psychotherapy is a decidedly human endeavor, and thus the application of modern technology to therapy must capitalize on-and enhance-our human capacities as counselors, students, and supervisors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Control, synchronization, and enhanced reliability of aperiodic oscillations in the Mercury Beating Heart system

    Science.gov (United States)

    Kumar, Pawan; Parmananda, P.

    2018-04-01

    Experiments involving the Mercury Beating Heart (MBH) oscillator, exhibiting irregular (aperiodic) dynamics, are performed. In the first set of experiments, control over irregular dynamics of the MBH oscillator was obtained via a superimposed periodic voltage signal. These irregular (aperiodic) dynamics were recovered once the control was switched off. Subsequently, two MBH oscillators were coupled to attain synchronization of their aperiodic oscillations. Finally, two uncoupled MBH oscillators were subjected, repeatedly, to a common stochastic forcing, resulting in an enhancement of their mutual phase correlation.

  2. Myocardial bridges of the coronary arteries in the human fetal heart.

    Science.gov (United States)

    Cakmak, Yusuf Ozgür; Cavdar, Safiye; Yalin, Aymelek; Yener, Nuran; Ozdogmus, Omer

    2010-09-01

    During the last century, many investigators reported on myocardial bridges in the adult human heart. In the present study, 39 human fetal hearts (the mean gestastional age was 30 weeks) were studied for myocardial bridging, and the results were correlated with adult data. Among the 39 (27 male and 12 female) fetal hearts studied, 26 bridges were observed on 18 fetal hearts (46.2%). Ten of the bridges had one myocardial bridge, whereas double myocardial bridges were observed in eight fetal hearts. The most frequent myocardial bridges were observed on the left anterior descending artery (LAD), which had 13 bridges (50%). Eight (30.7%) myocardial bridges were on the diagonal artery, and on the posterior descending artery there were five (19.3%). Myocardial bridges were not observed on the circumflex artery. The data presented in this study may provide potentially useful information for the preoperative evaluation of the newborn and may have a clinical implication for sudden fetal death.

  3. Electrical admittance for filling of the heart during lower body negative pressure in humans

    DEFF Research Database (Denmark)

    Cai, Yujia; Holm, S; Jenstrup, M

    2000-01-01

    To evaluate whether electrical admittance of intracellular water is applicable for monitoring filling of the heart, we determined the difference in intracellular water in the thorax (Thorax(ICW)), measured as the reciprocal value of the electrical impedance for the thorax at 1.5 and 100 kHz during...... lower body negative pressure (LBNP) in humans. Changes in Thorax(ICW) were compared with positron emission tomography-determined C(15)O-labeled erythrocytes over the heart. During -40 mmHg LBNP, the blood volume of the heart decreased by 21 +/- 3% as the erythrocyte volume was reduced by 20 +/- 2.......6 to 40.9 +/- 5.0 S. 10(-4); P = 0.08). The correlation between Thorax(ICW) and heart erythrocyte volume was 0.84 (P electrical admittance of intracellular water can be applied to evaluate changes in blood volume of the heart during LBNP in humans....

  4. Visualization of Fiber Structure in the Left and Right Ventricle of a Human Heart

    International Nuclear Information System (INIS)

    Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

    2006-01-01

    The human heart is composed of a helical network of muscle fibers. Anisotropic least squares filtering followed by fiber tracking techniques were applied to Diffusion Tensor Magnetic Resonance Imaging(DTMRI) data of the excised human heart. The fiber configuration was visualized by using thin tubes to increase 3-dimensional visual perception of the complex structure. All visualizations were performed using the high-quality ray-tracing software POV-Ray. The fibers are shown within the left and right ventricles. Both ventricles exhibit similar fiber architecture and some bundles of fibers are shown linking right and left ventricles on the posterior region of the heart

  5. Region and cell-type resolved quantitative proteomic map of the human heart

    DEFF Research Database (Denmark)

    Doll, Sophia; Dreßen, Martina; Geyer, Philipp E

    2017-01-01

    The heart is a central human organ and its diseases are the leading cause of death worldwide, but an in-depth knowledge of the identity and quantity of its constituent proteins is still lacking. Here, we determine the healthy human heart proteome by measuring 16 anatomical regions and three major...... cardiac cell types by high-resolution mass spectrometry-based proteomics. From low microgram sample amounts, we quantify over 10,700 proteins in this high dynamic range tissue. We combine copy numbers per cell with protein organellar assignments to build a model of the heart proteome at the subcellular...

  6. Total lymphatic irradiation and bone marrow in human heart transplantation

    International Nuclear Information System (INIS)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-01-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem

  7. Agonist of inward rectifier K+ channels enhances the protection of ischemic postconditioning in isolated rat hearts.

    Science.gov (United States)

    Liao, Z; Feng, Z; Long, C

    2014-07-01

    Selective inhibition of inward rectifier K + channels could abolish the protection mediated by ischemic preconditioning, but the roles of these channels in ischemic postconditioning have not been well characterized. Our study aims to evaluate the effect of inward rectifier K + channels on the protection induced by ischemic postconditioning. Langendorff-perfused rat hearts (n=8 per group) were split into four groups: postconditioning hearts (IPO group); ischemic postconditioning with BaCl 2 hearts (PB group); ischemic postconditioning with zacopride hearts (PZ group); and without ischemic postconditioning (CON group). After suffering 30 minutes of global ischemia, groups IPO, PB and PZ went through 10 seconds of ischemic postconditioning with three different perfusates: respectively, Krebs-Henseleit buffer (IPO group); 20 μmol/L BaCl 2 (antagonist of the channel, PB group); 1 μmol/L zacopride (agonist of the channel, PZ group). At the end of reperfusion, the myocardial performance was better preserved in the PZ group than the other three groups. The PB group showed no significant differences from the CON group. Our study has shown that the I K1 channel agonist zacopride is associated with the enhancement of ischemic postconditioning. © The Author(s) 2014.

  8. Human technology after cardiac epigenesis. Artificial heart versus cardiac transplantation.

    Science.gov (United States)

    Losman, J G

    1977-09-24

    Cardiovascular disease is the chief cause of death in technologically advanced countries and accounts for more than 50% of all deaths in the USA. For a patient with end-stage cardiac failure the only treatment presently available is organ replacement, either by transplantation or by the use of a mechanical heart. Transplantation has demonstrated its value: survival of more than 8 years and restoration of a normal quality of life to patients who were in end-stage cardiac decompensation. However, the prospect of routine clinical application of an artificial heart remains distant. The development of a totally implantable artificial heart still presents a series of challenging engineering problems with regard to strict constraints of size, weight, blood-material compatibility, adaptability of output to demand, efficiency and reliability of the power supply, and safety if nuclear fuel is used. The totally artificial heart is presently not an alternative to the cardiac allograft, but could provide short-term support for patients awaiting cardiac transplantation.

  9. Enhancing Human Cognition with Cocoa Flavonoids

    Directory of Open Access Journals (Sweden)

    Valentina Socci

    2017-05-01

    Full Text Available Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects.

  10. Human body region enhancement method based on Kinect infrared imaging

    Science.gov (United States)

    Yang, Lei; Fan, Yubo; Song, Xiaowei; Cai, Wenjing

    2016-10-01

    To effectively improve the low contrast of human body region in the infrared images, a combing method of several enhancement methods is utilized to enhance the human body region. Firstly, for the infrared images acquired by Kinect, in order to improve the overall contrast of the infrared images, an Optimal Contrast-Tone Mapping (OCTM) method with multi-iterations is applied to balance the contrast of low-luminosity infrared images. Secondly, to enhance the human body region better, a Level Set algorithm is employed to improve the contour edges of human body region. Finally, to further improve the human body region in infrared images, Laplacian Pyramid decomposition is adopted to enhance the contour-improved human body region. Meanwhile, the background area without human body region is processed by bilateral filtering to improve the overall effect. With theoretical analysis and experimental verification, the results show that the proposed method could effectively enhance the human body region of such infrared images.

  11. Cardiac spheroids as promising in vitro models to study the human heart microenvironment

    DEFF Research Database (Denmark)

    Polonchuk, Liudmila; Chabria, Mamta; Badi, Laura

    2017-01-01

    Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart ("cardiac spheroids", CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells an...

  12. Imaging of the human heart after administration of l-(N-13)glutamate

    International Nuclear Information System (INIS)

    Gelbard, A.S.; Benua, R.S.; Reiman, R.E.; McDonald, J.M.; Vomero, J.J.; Laughlin, J.S.

    1980-01-01

    In normal volunteers and cancer patients, studies using L-(N-13)glutamate as an imaging agent showed localization of N-13 activity in the heart. Other organs that were well visualized include the liver, pancreas, and salivary glands. The concentration of N-13 activity in the human heart could not be predicted from previous studies involving myocardial uptake in dogs and rodents after administration of L-(N-13)glutamate

  13. 3D-shaded surface rendering of gadolinium-enhanced MR angiography in congenital heart disease

    International Nuclear Information System (INIS)

    Okuda, S.; Kikinis, R.; Dumanli, H.; Geva, T.; Powell, A.J.; Chung, T.

    2000-01-01

    Background. Gadolinium-enhanced three-dimensional (3D) MR angiography is a useful imaging technique for patients with congenital heart disease. Objective. This study sought to determine the added value of creating 3D shaded surface displays compared to standard maximal intensity projection (MIP) and multiplanar reformatting (MPR) techniques when analyzing 3D MR angiography data. Materials and methods. Seventeen patients (range, 3 months to 51 years old) with a variety of congenital cardiovascular defects underwent gadolinium-enhanced 3D MR angiography of the thorax. Color-coded 3D shaded surface models were rendered from the image data using manual segmentation and computer-based algorithms. Models could be rotated, translocated, or zoomed interactively by the viewer. Information available from the 3D models was compared to analysis based on viewing standard MIP/MPR displays. Results. Median postprocessing time for the 3D models was 6 h (range, 3-25 h) compared to approximately 20 min for MIP/MPR viewing. No additional diagnostic information was gained from 3D model analysis. All major findings with MIP/MPR postprocessing were also apparent on the 3D models. Qualitatively, the 3D models were more easily interpreted and enabled adjacent vessels to be distinguished more readily. Conclusion. Routine use of 3D shaded surface reconstructions for visualization of contrast enhanced MR angiography in congenital heart disease cannot be recommended. 3D surface rendering may be more useful for presenting complex anatomy to an audience unfamiliar with congenital heart disease and as an educational tool. (orig.)

  14. Public opinions about human enhancement can enhance the expert-only debate. A review study

    NARCIS (Netherlands)

    Dijkstra, Anne M.; Schuijff, Mirjam

    2016-01-01

    Human enhancement, the non-medical use of biomedical technologies to improve the human body or performance beyond their ‘natural’ limitations, is a growing trend. At the same time, the use of these technologies has societal consequences. In societal debates about human enhancement, however, it is

  15. Triboelectric Nanogenerator Enabled Body Sensor Network for Self-Powered Human Heart-Rate Monitoring.

    Science.gov (United States)

    Lin, Zhiming; Chen, Jun; Li, Xiaoshi; Zhou, Zhihao; Meng, Keyu; Wei, Wei; Yang, Jin; Wang, Zhong Lin

    2017-09-26

    Heart-rate monitoring plays a critical role in personal healthcare management. A low-cost, noninvasive, and user-friendly heart-rate monitoring system is highly desirable. Here, a self-powered wireless body sensor network (BSN) system is developed for heart-rate monitoring via integration of a downy-structure-based triboelectric nanogenerator (D-TENG), a power management circuit, a heart-rate sensor, a signal processing unit, and Bluetooth module for wireless data transmission. By converting the inertia energy of human walking into electric power, a maximum power of 2.28 mW with total conversion efficiency of 57.9% was delivered at low operation frequency, which is capable of immediately and sustainably driving the highly integrated BSN system. The acquired heart-rate signal by the sensor would be processed in the signal process circuit, sent to an external device via the Bluetooth module, and displayed on a personal cell phone in a real-time manner. Moreover, by combining a TENG-based generator and a TENG-based sensor, an all-TENG-based wireless BSN system was developed, realizing continuous and self-powered heart-rate monitoring. This work presents a potential method for personal heart-rate monitoring, featured as being self-powered, cost-effective, noninvasive, and user-friendly.

  16. Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

    OpenAIRE

    Singh, Sanjay; Sayers, Scott; Walter, James S.; Thomas, Donald; Dieter, Robert S.; Nee, Lisa M.; Wurster, Robert D.

    2013-01-01

    Background Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hyper...

  17. Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts.

    Science.gov (United States)

    Gergs, Ulrich; Jung, Franziska; Buchwalow, Igor B; Hofmann, Britt; Simm, Andreas; Treede, Hendrik; Neumann, Joachim

    2017-12-01

    Using transgenic (TG) mice that overexpress the human serotonin (5-HT) 4a receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor 5-hydroxy-tryptophan (5-HTP) can exert inotropic and chronotropic effects in cardiac preparations from TG mice but not from wild-type (WT) mice; similar results were found in human atrial preparations as well as in intact TG animals using echocardiography. Moreover, by immunohistochemistry we could detect 5-HT metabolizing enzymes and 5-HT transporters in mouse hearts as well as in human atria. Hence, in the presence of an inhibitor of aromatic l-amino acid decarboxylase, the positive inotropic effects of 5-HTP were absent in TG and isolated human atrial preparations, and, moreover, inhibitors of enzymes involved in 5-HT degradation enhanced the efficacy of 5-HT in TG atria. A releaser of neurotransmitters increased inotropy in the isolated TG atrium, and this effect could be blocked by a 5-HT 4a receptor antagonist. Fluoxetine, an inhibitor of 5-HT uptake, elevated the potency of 5-HT to increase contractility in the TG atrium. In addition, inhibitors of organic cation and monoamine transporters apparently reduced the positive inotropic potency of 5-HT in the TG atrium. Hence, we tentatively conclude that a local production and degradation of 5-HT in the mammalian heart and more specifically in mammalian myocytes probably occurs. Conceivably, this formation of 5-HT and possibly impaired degradation may be clinically relevant in cases of unexplained tachycardia and other arrhythmias. NEW & NOTEWORTHY The present work suggests that inotropically active serotonin (5-HT) can be formed in the mouse and human heart and probably by cardiomyocytes themselves. Moreover, active degradation of 5-HT seems to occur in the mammalian heart. These findings may again

  18. The Development of Marine Accidents Human Reliability Assessment Approach: HEART Methodology and MOP Model

    Directory of Open Access Journals (Sweden)

    Ludfi Pratiwi Bowo

    2017-06-01

    Full Text Available Humans are one of the important factors in the assessment of accidents, particularly marine accidents. Hence, studies are conducted to assess the contribution of human factors in accidents. There are two generations of Human Reliability Assessment (HRA that have been developed. Those methodologies are classified by the differences of viewpoints of problem-solving, as the first generation and second generation. The accident analysis can be determined using three techniques of analysis; sequential techniques, epidemiological techniques and systemic techniques, where the marine accidents are included in the epidemiological technique. This study compares the Human Error Assessment and Reduction Technique (HEART methodology and the 4M Overturned Pyramid (MOP model, which are applied to assess marine accidents. Furthermore, the MOP model can effectively describe the relationships of other factors which affect the accidents; whereas, the HEART methodology is only focused on human factors.

  19. Human enhancement and communication: on meaning and shared understanding.

    Science.gov (United States)

    Cabrera, Laura; Weckert, John

    2013-09-01

    Our technologies have enabled us to change both the world and our perceptions of the world, as well as to change ourselves and to find new ways to fulfil the human desire for improvement and for having new capacities. The debate around using technology for human enhancement has already raised many ethical concerns, however little research has been done in how human enhancement can affect human communication. The purpose of this paper is to explore whether some human enhancements could change our shared lifeworld so radically that human communication as we know it would not be possible any longer. After exploring the kinds of communication problems we are concerned with as well as mentioning some possible enhancement interventions that could bring about such problems, we will address some of the ethical implications that follow from these potential communication problems. We argue that because of the role that communication plays in human society, this issue deserves attention.

  20. Carvedilol Enhances the Antioxidant Effect of Vitamins E and C in Chronic Chagas Heart Disease

    International Nuclear Information System (INIS)

    Budni, Patrícia; Pedrosa, Roberto Coury; Dalmarco, Eduardo Monguilhott; Dalmarco, Juliana Bastos; Frode, Tânia Sílvia; Wilhelm, Danilo Filho

    2013-01-01

    Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. The decrease in oxidative

  1. Carvedilol Enhances the Antioxidant Effect of Vitamins E and C in Chronic Chagas Heart Disease

    Energy Technology Data Exchange (ETDEWEB)

    Budni, Patrícia, E-mail: budnip@gmail.com [Universidade Federal de Santa Catarina, Florianópolis, SC (Brazil); Pedrosa, Roberto Coury [Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil); Dalmarco, Eduardo Monguilhott; Dalmarco, Juliana Bastos; Frode, Tânia Sílvia; Wilhelm, Danilo Filho [Universidade Federal de Santa Catarina, Florianópolis, SC (Brazil)

    2013-10-15

    Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. The decrease in oxidative

  2. Post-study caffeine administration enhances memory consolidation in humans.

    Science.gov (United States)

    Borota, Daniel; Murray, Elizabeth; Keceli, Gizem; Chang, Allen; Watabe, Joseph M; Ly, Maria; Toscano, John P; Yassa, Michael A

    2014-02-01

    It is currently not known whether caffeine has an enhancing effect on long-term memory in humans. We used post-study caffeine administration to test its effect on memory consolidation using a behavioral discrimination task. Caffeine enhanced performance 24 h after administration according to an inverted U-shaped dose-response curve; this effect was specific to consolidation and not retrieval. We conclude that caffeine enhanced consolidation of long-term memories in humans.

  3. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.

    Science.gov (United States)

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a 'wildlife photographer', resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds.

  4. Estimation of human core temperature from sequential heart rate observations

    International Nuclear Information System (INIS)

    Buller, Mark J; Tharion, William J; Cheuvront, Samuel N; Montain, Scott J; Kenefick, Robert W; Castellani, John; Latzka, William A; Hoyt, Reed W; Roberts, Warren S; Richter, Mark; Jenkins, Odest Chadwicke

    2013-01-01

    Core temperature (CT) in combination with heart rate (HR) can be a good indicator of impending heat exhaustion for occupations involving exposure to heat, heavy workloads, and wearing protective clothing. However, continuously measuring CT in an ambulatory environment is difficult. To address this problem we developed a model to estimate the time course of CT using a series of HR measurements as a leading indicator using a Kalman filter. The model was trained using data from 17 volunteers engaged in a 24 h military field exercise (air temperatures 24–36 °C, and 42%–97% relative humidity and CTs ranging from 36.0–40.0 °C). Validation data from laboratory and field studies (N = 83) encompassing various combinations of temperature, hydration, clothing, and acclimation state were examined using the Bland–Altman limits of agreement (LoA) method. We found our model had an overall bias of −0.03 ± 0.32 °C and that 95% of all CT estimates fall within ±0.63 °C (>52 000 total observations). While the model for estimating CT is not a replacement for direct measurement of CT (literature comparisons of esophageal and rectal methods average LoAs of ±0.58 °C) our results suggest it is accurate enough to provide practical indication of thermal work strain for use in the work place. (paper)

  5. Estimation of human core temperature from sequential heart rate observations.

    Science.gov (United States)

    Buller, Mark J; Tharion, William J; Cheuvront, Samuel N; Montain, Scott J; Kenefick, Robert W; Castellani, John; Latzka, William A; Roberts, Warren S; Richter, Mark; Jenkins, Odest Chadwicke; Hoyt, Reed W

    2013-07-01

    Core temperature (CT) in combination with heart rate (HR) can be a good indicator of impending heat exhaustion for occupations involving exposure to heat, heavy workloads, and wearing protective clothing. However, continuously measuring CT in an ambulatory environment is difficult. To address this problem we developed a model to estimate the time course of CT using a series of HR measurements as a leading indicator using a Kalman filter. The model was trained using data from 17 volunteers engaged in a 24 h military field exercise (air temperatures 24-36 °C, and 42%-97% relative humidity and CTs ranging from 36.0-40.0 °C). Validation data from laboratory and field studies (N = 83) encompassing various combinations of temperature, hydration, clothing, and acclimation state were examined using the Bland-Altman limits of agreement (LoA) method. We found our model had an overall bias of -0.03 ± 0.32 °C and that 95% of all CT estimates fall within ±0.63 °C (>52 000 total observations). While the model for estimating CT is not a replacement for direct measurement of CT (literature comparisons of esophageal and rectal methods average LoAs of ±0.58 °C) our results suggest it is accurate enough to provide practical indication of thermal work strain for use in the work place.

  6. Developing theological tools for a strategic engagement with Human Enhancement.

    Science.gov (United States)

    Tomkins, Justin

    2014-01-01

    The literature on Human Enhancement may indeed have reached a critical mass yet theological engagement with the subject is still thin. Human Enhancement has already been established as a key topic within research and captivating visions of the future have been allied with a depth of philosophical analysis. Some Transhumanists have pointed to a theological dimension to their position and some who have warned against enhancement might be seen as having done so from a perspective shaped by a Judeo-Christian worldview. Nonetheless, in neither of these cases has theology been central to engagement with the enhancement quest.Christian theologians who have begun to open up such an engagement with Human Enhancement include Brent Waters, Robert Song and Celia Deane-Drummond. The work they have already carried out is insightful and important yet due to the scale of the possible engagement, the wealth of Christian theology which might be applied to Human Enhancement remains largely untapped. This paper explores how three key aspects of Christian theology, eschatology, love of God and love of neighbour, provide valuable tools for a theological engagement with Human Enhancement. It is proposed that such theological tools need to be applied to Human Enhancement if the debate is to be resourced with the Christian theological perspective of what it means to be human in our contemporary technological context and if society is to have the choice of maintaining its Christian foundations.

  7. Limits to human enhancement: nature, disease, therapy or betterment?

    Science.gov (United States)

    Hofmann, Bjørn

    2017-10-10

    New technologies facilitate the enhancement of a wide range of human dispositions, capacities, or abilities. While it is argued that we need to set limits to human enhancement, it is unclear where we should find resources to set such limits. Traditional routes for setting limits, such as referring to nature, the therapy-enhancement distinction, and the health-disease distinction, turn out to have some shortcomings. However, upon closer scrutiny the concept of enhancement is based on vague conceptions of what is to be enhanced. Explaining why it is better to become older, stronger, and more intelligent presupposes a clear conception of goodness, which is seldom provided. In particular, the qualitative better is frequently confused with the quantitative more. We may therefore not need "external" measures for setting its limits - they are available in the concept of enhancement itself. While there may be shortcomings in traditional sources of limit setting to human enhancement, such as nature, therapy, and disease, such approaches may not be necessary. The specification-of-betterment problem inherent in the conception of human enhancement itself provides means to restrict its unwarranted proliferation. We only need to demand clear, sustainable, obtainable goals for enhancement that are based on evidence, and not on lofty speculations, hypes, analogies, or weak associations. Human enhancements that specify what will become better, and provide adequate evidence, are good and should be pursued. Others should not be accepted.

  8. Do anabolic nutritional supplements stimulate human growth hormone secretion in elderly women with heart failure?

    NARCIS (Netherlands)

    Smeets, Ellen T.H.C.; Schutzler, Scott E.; Wei, Jeanne Y.; Azhar, Gohar; Wolfe, Robert R.

    2017-01-01

    Growth hormone treatment has gained attention over the past decade as a treatment for heart failure. Human growth hormone (HGH) must be administered by injections (usually daily), so there is considerable advantage to stimulation of endogenous secretion by amino acid-based nutritional

  9. Visualization of human heart conduction system by means of fluorescence spectroscopy

    Science.gov (United States)

    Venius, Jonas; Bagdonas, Saulius; Žurauskas, Edvardas; Rotomskis, Ricardas

    2011-10-01

    The conduction system of the heart is a specific muscular tissue, where a heartbeat signal originates and initiates the depolarization of the ventricles. The muscular origin makes it complicated to distinguish the conduction system from the surrounding tissues. A surgical intervention can lead to the accidental harm of the conduction system, which may eventually result in a dangerous obstruction of the heart functionality. Therefore, there is an immense necessity for developing a helpful method to visualize the conduction system during the operation time. The specimens for the spectroscopic studies were taken from nine diverse human hearts. The localization of distinct types of the tissue was preliminary marked by the pathologist and approved histologically after the spectral measurements. Variations in intensity, as well as in shape, were detected in autofluorescence spectra of different heart tissues. The most distinct differences were observed between the heart conduction system and the surrounding tissues under 330 and 380 nm excitation. The spectral region around 460 nm appeared to be the most suitable for an unambiguous differentiation of the human conduction system avoiding the absorption peak of blood. The visualization method, based on the intensity ratios calculated for two excitation wavelengths, was also demonstrated.

  10. Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats.

    Science.gov (United States)

    Stern, Javier E; Potapenko, Evgeniy S

    2013-08-15

    An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and presympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca²⁺ imaging to determine whether altered N-methyl-d-aspartate (NMDA) receptor-mediated changes in intracellular Ca²⁺ levels (NMDA-ΔCa²⁺) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ΔCa²⁺ in MNCs from HF when compared with sham rats. The enhanced NMDA-ΔCa²⁺ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca²⁺ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca²⁺ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ΔCa²⁺ signaling during HF are discussed.

  11. Haploinsufficiency of TAB2 causes congenital heart defects in humans

    DEFF Research Database (Denmark)

    Thienpont, Bernard; Zhang, Litu; Postma, Alex V

    2010-01-01

    . To definitively confirm the role of this candidate gene in CHDs, we performed mutation analysis of TAB2 in 402 patients with a CHD, which revealed two evolutionarily conserved missense mutations. Finally, a balanced translocation was identified, cosegregating with familial CHD. Mapping of the breakpoints...... demonstrated that this translocation disrupts TAB2. Taken together, these data clearly demonstrate a role for TAB2 in human cardiac development....

  12. E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells

    OpenAIRE

    Lee, Hyun-Wook; Park, Sung-Hyun; Weng, Mao-wen; Wang, Hsiang-Tsui; Huang, William C.; Lepor, Herbert; Wu, Xue-Ru; Chen, Lung-Chi; Tang, Moon-shong

    2018-01-01

    Significance E-cigarette smoke (ECS) delivers nicotine through aerosols without burning tobacco. ECS is promoted as noncarcinogenic. We found that ECS induces DNA damage in mouse lung, bladder, and heart and reduces DNA-repair functions and proteins in lung. Nicotine and its nitrosation product 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone can cause the same effects as ECS and enhance mutations and tumorigenic cell transformation in cultured human lung and bladder cells. These results indica...

  13. Na+,K+-ATPase concentration in rodent and human heart and skeletal muscle

    DEFF Research Database (Denmark)

    Kjeldsen, K; Bjerregaard, P; Richter, Erik

    1988-01-01

    rats, cardiomyopathic hamsters, and human subjects. These methods have earlier been shown to quantify the Na+,K+-ATPase concentration in muscle tissue with high accuracy. When rats were swim trained for six weeks the heart ventricular muscle Na+,K+-ATPase concentration was increased by 20% (p less than...... was increased by up to 46% (p less than 0.001) and decreased by up to 30% (p less than 0.005) after training and immobilisation respectively. Cardiomyopathic hamsters showed a reduction of 33% (p less than 0.005) in the heart ventricular Na+,K+-ATPase concentration compared with normal hamsters. This decrease...

  14. Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

    Science.gov (United States)

    Tylutki, Zofia; Polak, Sebastian

    2015-03-12

    Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    Science.gov (United States)

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  16. Psychology: red enhances human performance in contests.

    Science.gov (United States)

    Hill, Russell A; Barton, Robert A

    2005-05-19

    Red coloration is a sexually selected, testosterone-dependent signal of male quality in a variety of animals, and in some non-human species a male's dominance can be experimentally increased by attaching artificial red stimuli. Here we show that a similar effect can influence the outcome of physical contests in humans--across a range of sports, we find that wearing red is consistently associated with a higher probability of winning. These results indicate not only that sexual selection may have influenced the evolution of human response to colours, but also that the colour of sportswear needs to be taken into account to ensure a level playing field in sport.

  17. The quantitative assessment of epicardial fat distribution on human hearts: Implications for epicardial electrophysiology.

    Science.gov (United States)

    Mattson, Alexander R; Soto, Mario J; Iaizzo, Paul A

    2018-07-01

    Epicardial electrophysiological procedures rely on dependable interfacing with the myocardial tissue. For example, epicardial pacing systems must generate sustainable chronic pacing capture, while epicardial ablations must effectively deliver energy to the target hyper-excitable myocytes. The human heart has a significant adipose layer which may impede epicardial procedures. The objective of this study was to quantitatively assess the relative location of epicardial adipose on the human heart, to define locations where epicardial therapies might be performed successfully. We studied perfusion-fixed human hearts (n = 105) in multiple isolated planes including: left ventricular margin, diaphragmatic surface, and anterior right ventricle. Relative adipose distribution was quantitatively assessed via planar images, using a custom-generated image analysis algorithm. In these specimens, 76.7 ± 13.8% of the left ventricular margin, 72.7 ± 11.3% of the diaphragmatic surface, and 92.1 ± 8.7% of the anterior right margin were covered with superficial epicardial adipose layers. Percent adipose coverage significantly increased with age (P history of coronary artery disease (P history of hypertension, and/or history of congestive heart failure. Additionally, we describe two-dimensional probability distributions of epicardial adipose coverage for each of the three analysis planes. In this study, we detail the quantitative assessment and probabilistic mapping of the distribution of superficial epicardial adipose on the adult human heart. These findings have implications relative to performing epicardial procedures and/or designing procedures or tools to successfully perform such treatments. Clin. Anat. 31:661-666, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  18. Fractionated magnetic-resonance elastography on the human heart; Fraktionierte Magnetresonanzelastographie am menschlichen Herzen

    Energy Technology Data Exchange (ETDEWEB)

    Rump, Jens

    2008-07-28

    Imaging techniques, including magnetic resonance imaging, belong to the most important tools in modern medical diagnostics. Another diagnostic aid is palpation, which is suitable for the qualitative characterization of pathological changes in organs near the surface. Magnetic resonance elastography (MRE) is a combination of these techniques. In principle, MRE uses motionsensitive MR-imaging to depict tissue deformation caused by externally induced shear waves. The type of deformation supply useful information about the elasticity of the tissue. Cardiac disorders are among the most common diseases. The goal of this study was to develop a method of applying in-vivo MRE to the human heart. The development of the mechanical stimulus, ultimately resulting in the introduction of an audio speaker as the source of vibration, provided the necessary means to introduce vibrations into inner organs. A crucial factor in applying MRE to the heart is the speed of the recording, which led to the development of 'fractional MRE'. The currently conventional fast heart imaging techniques were used as a starting point. The use of an unbalanced phase preparation gradient in the balanced steady-state imaging technique resulted in an improved phase-to-noise ratio. Along with the spoiled steady-state MRE imaging technique, initial MRE-studies on the human heart were performed. For the first time, externally induced mechanical vibrations were successfully introduced into the heart and were detected using fractional MRE with a high temporal resolution. The modulation of the shear wave amplitudes observed in the myocard of 6 healthy subjects correlated with the phases of the cardiac cycle. The techniques and methods developed here are a step toward routine clinical application of MRE of the heart and indicate high potential in the area of early diagnosis of cardiac disease. (orig.)

  19. Can stem cells really regenerate the human heart? Use your noggin, dickkopf! Lessons from developmental biology.

    Science.gov (United States)

    Sommer, Paula

    2013-06-01

    The human heart is the first organ to develop and its development is fairly well characterised. In theory, the heart has the capacity to regenerate, as its cardiomyocytes may be capable of cell division and the adult heart contains a cardiac stem cell niche, presumably capable of differentiating into cardiomyocytes and other cardiac-associated cell types. However, as with most other organs, these mechanisms are not activated upon serious injury. Several experimental options to induce regeneration of the damaged heart tissue are available: activate the endogenous cardiomyocytes to divide, coax the endogenous population of stem cells to divide and differentiate, or add exogenous cell-based therapy to replace the lost cardiac tissue. This review is a summary of the recent research into all these avenues, discussing the reasons for the limited successes of clinical trials using stem cells after cardiac injury and explaining new advances in basic science. It concludes with a reiteration that chances of successful regeneration would be improved by understanding and implementing the basics of heart development and stem cell biology.

  20. Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

    2017-05-09

    Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

  1. Testing to Enhance Retention in Human Anatomy

    Science.gov (United States)

    Logan, Jessica M.; Thompson, Andrew J.; Marshak, David W.

    2011-01-01

    Recent work in cognitive psychology has shown that repeatedly testing one's knowledge is a powerful learning aid and provides substantial benefits for retention of the material. To apply this in a human anatomy course for medical students, 39 fill-in-the-blank quizzes of about 50 questions each, one for each region of the body, and four about the…

  2. Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure.

    Science.gov (United States)

    Xu, Bo; Zheng, Hong; Patel, Kaushik P

    2012-04-15

    Previous studies have indicated that there is increased activation of the paraventricular nucleus (PVN) in rats with chronic heart failure (CHF); however, it is not clear if the preautonomic neurons within the PVN are specifically overactive. Also, it is not known if these neurons have altered responses to baroreceptor or osmotic challenges. Experiments were conducted in rats with CHF (6-8 wk after coronary artery ligation). Spontaneously active neurons were recorded in the PVN, of which 36% were antidromically activated from the rostral ventrolateral medulla (RVLM). The baseline discharge rate in RVLM-projecting PVN (PVN-RVLM) neurons from CHF rats was significantly greater than in sham-operated (sham) rats (6.0 ± 0.6 vs. 2.6 ± 0.3 spikes/s, P neurons by 80% in CHF rats compared with 37% in sham rats. Fifty-two percent of spontaneously active PVN-RVLM neurons responded to changes in the mean arterial pressure (MAP). The changes in discharge rate in PVN-RVLM neurons after a reduction in MAP (+52 ± 7% vs. +184 ± 61%) or an increase in MAP (-42 ± 8% vs. -71 ± 6%) were significantly attenuated in rats with CHF compared with sham rats. Most PVN-RVLM neurons (63%), including all barosensitive PVN-RVLM neurons, were excited by an internal carotid artery injection of hypertonic NaCl (2.1 osmol/l), whereas a smaller number (7%) were inhibited. The increase in discharge rate in PVN-RVLM neurons to hypertonic stimulation was significantly enhanced in rats with CHF compared with sham rats (134 ± 15% vs. 92 ± 13%). Taken together, these data suggest that PVN-RVLM neurons are more active under basal conditions and this overactivation is mediated by an enhanced glutamatergic tone in rats with CHF. Furthermore, this enhanced activation of PVN-RVLM neurons may contribute to the altered responses to baroreceptor and osmotic challenges observed during CHF.

  3. Tracking fusion of human mesenchymal stem cells after transplantation to the heart.

    Science.gov (United States)

    Freeman, Brian T; Kouris, Nicholas A; Ogle, Brenda M

    2015-06-01

    Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid recovery of damaged myocardium caused by myocardial infarction. One possible mechanism for MSC-mediated recovery is reprogramming after cell fusion between transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging to detect fusion of transplanted human pluripotent stem cell-derived MSCs to cells of organs of living mice. Human MSCs, with transient expression of a viral fusogen, were delivered to the murine heart via a collagen patch. At 2 days and 1 week later, living mice were probed for bioluminescence indicative of cell fusion. Cell fusion was detected at the site of delivery (heart) and in distal tissues (i.e., stomach, small intestine, liver). Fusion was confirmed at the cellular scale via fluorescence in situ hybridization for human-specific and mouse-specific centromeres. Human cells in organs distal to the heart were typically located near the vasculature, suggesting MSCs and perhaps MSC fusion products have the ability to migrate via the circulatory system to distal organs and engraft with local cells. The present study reveals previously unknown migratory patterns of delivered human MSCs and associated fusion products in the healthy murine heart. The study also sets the stage for follow-on studies to determine the functional effects of cell fusion in a model of myocardial damage or disease. Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other tissues to recover lost function or at least limit overactive immune responses. Analysis of tissues after MSC transplantation shows evidence of fusion between MSCs and the cells of the recipient. To date, the biologic implications of cell fusion remain unclear. A newly developed in vivo tracking system was used to identify MSC fusion products in living mice. The migratory patterns of fusion products were determined both in the target organ (i

  4. Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

    Science.gov (United States)

    Singh, Sanjay; Sayers, Scott; Walter, James S; Thomas, Donald; Dieter, Robert S; Nee, Lisa M; Wurster, Robert D

    2013-08-19

    Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); Phearts (767.80±18.37 versus 650.23±9.84 μm(2); Pneurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); Pneurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

  5. Nocturnal variations in peripheral blood flow, systemic blood pressure, and heart rate in humans

    DEFF Research Database (Denmark)

    Sindrup, J H; Kastrup, J; Christensen, H

    1991-01-01

    Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage uni.......0001). The synchronism of the nocturnal subcutaneous hyperemia and the decrease in systemic mean arterial blood pressure point to a common, possibly central nervous or humoral, eliciting mechanism.......Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage unit...

  6. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  7. Expressive Writing: Enhancing the Emotional Intelligence of Human Services Majors

    Science.gov (United States)

    Castillo, Yuleinys; Fischer, Jerome M.

    2017-01-01

    The skills and tasks in the human services field are highly connected to emotional intelligence abilities. The purpose of the study was to investigate the effect of an expressive writing program involving human service students in an undergraduate rehabilitation services course. The program was developed to enhance their emotional intelligence.…

  8. [Healthcare and Christianity, the human person at the heart of God's concerns].

    Science.gov (United States)

    Onfray, Jean-Marie

    2015-10-01

    French society is still influenced by its Christian traditions and many patients are attached to this aspect. It is therefore important to clarify the reference framework put forward by the Christian religion when dealing with the notions of health, illness and care in this context. The human person, with his/her strengths and weaknesses, is at the heart of Christian reflections. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Identification of Enhancers In Human: Advances In Computational Studies

    KAUST Repository

    Kleftogiannis, Dimitrios A.

    2016-03-24

    Roughly ~50% of the human genome, contains noncoding sequences serving as regulatory elements responsible for the diverse gene expression of the cells in the body. One very well studied category of regulatory elements is the category of enhancers. Enhancers increase the transcriptional output in cells through chromatin remodeling or recruitment of complexes of binding proteins. Identification of enhancer using computational techniques is an interesting area of research and up to now several approaches have been proposed. However, the current state-of-the-art methods face limitations since the function of enhancers is clarified, but their mechanism of function is not well understood. This PhD thesis presents a bioinformatics/computer science study that focuses on the problem of identifying enhancers in different human cells using computational techniques. The dissertation is decomposed into four main tasks that we present in different chapters. First, since many of the enhancer’s functions are not well understood, we study the basic biological models by which enhancers trigger transcriptional functions and we survey comprehensively over 30 bioinformatics approaches for identifying enhancers. Next, we elaborate more on the availability of enhancer data as produced by different enhancer identification methods and experimental procedures. In particular, we analyze advantages and disadvantages of existing solutions and we report obstacles that require further consideration. To mitigate these problems we developed the Database of Integrated Human Enhancers (DENdb), a centralized online repository that archives enhancer data from 16 ENCODE cell-lines. The integrated enhancer data are also combined with many other experimental data that can be used to interpret the enhancers content and generate a novel enhancer annotation that complements the existing integrative annotation proposed by the ENCODE consortium. Next, we propose the first deep-learning computational

  10. Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats.

    Science.gov (United States)

    Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

    2016-07-06

    Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1- Control 2- Heart Failure (HF) 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×10 6 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001). Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters.

  11. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

    Science.gov (United States)

    Ardehali, Abbas; Esmailian, Fardad; Deng, Mario; Soltesz, Edward; Hsich, Eileen; Naka, Yoshifumi; Mancini, Donna; Camacho, Margarita; Zucker, Mark; Leprince, Pascal; Padera, Robert; Kobashigawa, Jon

    2015-06-27

    The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. TransMedics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Enhanced preservation of the isolated rat heart after hypothermic storage by pinacidil pretreatment and storage in lazaroid U74500A

    International Nuclear Information System (INIS)

    Hicks, M.; Du, Z.Y.; Spratt, P.; Macdonald, P.

    1998-01-01

    The aim of the present study was to compare 3 protocols incorporating these approaches on the preservation of haemodynamic function in the isolated working rat heart after hypothermic storage. These protocols were: 1) pretreatment of the heart with 200 μM pinacidil, an ATP-sensitive potassium channel opener; 2) storage in cardioplegic solution containing the lipid soluble lazaroid antioxidant U74500A (30 μM); 3) A combination of protocols 1 and 2. Methods: Hearts from Wistar rats (250 to 330g body weight) were perfused on a Langendorff apparatus. Each heart was ligated to an aortic cannula and perfused retrogradely, with oxygenated Krebs solution at a hydrostatic pressure of 100 cm H 2 O. The system was then converted to 'working mode' by switching the perfusate from aorta to a left atrial cannula (filling pressure 15 cm H 2 O). After stabilisation, the following pre-arrest indices of cardiac function were recorded: heart rate (HR), coronary flow (CF), aortic flow (AF) and cardiac output (CO). Hearts were then randomised to protocols 1-3, untreated controls or vehicle treated controls (n=6 animals/ group). Hearts were stored in an extracellular-based preservation solution for 12 hours at 2-3degC, remounted on the perfusion apparatus and stabilised as before. Haemodynamic measurements were then repeated. Conclusions: Combined pharmacological activation of ATP-sensitive potassium channels before cardioplegia and the addition of U74500A to the preservation solution is associated with a significantly enhanced haemodynamic function in the rat heart after 12 hours of hypothermic storage. These data suggest a novel use for these agents in the transplantation context

  13. Enhanced preservation of the isolated rat heart after hypothermic storage by pinacidil pretreatment and storage in lazaroid U74500A

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, M. [St Vincent`s Hospital, Darlinghurst, NSW (Australia). Division of Clinical Pharmacology and Toxicology; Du, Z.Y.; Spratt, P.; Macdonald, P. [St Vincent`s Hospital, Darlinghurst, NSW (Australia). Cardiopulmonary Transplant Unit

    1998-12-31

    The aim of the present study was to compare 3 protocols incorporating these approaches on the preservation of haemodynamic function in the isolated working rat heart after hypothermic storage. These protocols were: 1) pretreatment of the heart with 200 {mu}M pinacidil, an ATP-sensitive potassium channel opener; 2) storage in cardioplegic solution containing the lipid soluble lazaroid antioxidant U74500A (30 {mu}M); 3) A combination of protocols 1 and 2. Methods: Hearts from Wistar rats (250 to 330g body weight) were perfused on a Langendorff apparatus. Each heart was ligated to an aortic cannula and perfused retrogradely, with oxygenated Krebs solution at a hydrostatic pressure of 100 cm H{sub 2}O. The system was then converted to `working mode` by switching the perfusate from aorta to a left atrial cannula (filling pressure 15 cm H{sub 2}O). After stabilisation, the following pre-arrest indices of cardiac function were recorded: heart rate (HR), coronary flow (CF), aortic flow (AF) and cardiac output (CO). Hearts were then randomised to protocols 1-3, untreated controls or vehicle treated controls (n=6 animals/ group). Hearts were stored in an extracellular-based preservation solution for 12 hours at 2-3degC, remounted on the perfusion apparatus and stabilised as before. Haemodynamic measurements were then repeated. Conclusions: Combined pharmacological activation of ATP-sensitive potassium channels before cardioplegia and the addition of U74500A to the preservation solution is associated with a significantly enhanced haemodynamic function in the rat heart after 12 hours of hypothermic storage. These data suggest a novel use for these agents in the transplantation context Truncated abstract. 1 tab.

  14. Evaluation of heart perfusion in patients with acute myocardial infarction using dynamic contrast-enhanced magnetic resonance imaging

    DEFF Research Database (Denmark)

    Nielsen, Gitte; Fritz-Hansen, Thomas; Dirks, Christina G

    2004-01-01

    with acute transmural myocardial infarction were studied using a Turbo-fast low angle shot (FLASH) MRI sequence to monitor the first pass of an extravascular contrast agent (CA), gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). Quantitation of perfusion, expressed as Ki (mL/100 g/minute), in five......PURPOSE: To investigate the diagnostic ability of quantitative magnetic resonance imaging (MRI) heart perfusion in acute heart patients, a fast, multislice dynamic contrast-enhanced MRI sequence was applied to patients with acute myocardial infarction. MATERIALS AND METHODS: Seven patients...

  15. Why higher economic growth cannot always enhance human development

    OpenAIRE

    Ahmed, Md Montasir

    2017-01-01

    This paper studies why higher economic growth cannot always enhance human development. In general, these two dimensions have a strong and positive relationship, but some countries appear unable to balance this relationship. As a consequence, there are some countries with high economic growth but sluggish human development progress. This paper studies how other factors besides GDP – women labor force participation, urbanization, and inequality - are correlated to human development. I construct...

  16. Enhanced human performance of utility maintenance programs

    International Nuclear Information System (INIS)

    Fresco, A.; Haber, S.; O'Brien, J.

    1993-01-01

    Assuring the safe operation of a nuclear power plant depends, to a large extent, on how effectively one understands and manages the aging-related degradation that occurs in structures, systems, and components (SSCs). Aging-related degradation is typically managed through a nuclear plant's maintenance program. A review of 44 Maintenance Team Inspection (MTI) Reports indicated that while some plant organizations appeared to assume a proactive mode in preventing aging-related failures of their SSCs important to safety, others seemed to be taking a passive or reactive mode. Across all plants, what is clearly needed, is a strong recognition of the importance of aging-related degradation and the use of existing organizational assets to effectively detect and mitigate those effects. Many of those assets can be enhanced by the consideration of organizational and management factors necessary for the implementation of an effective aging management program. This report provides a discussion of this program

  17. An Intervention to Enhance Goals-of-Care Communication Between Heart Failure Patients and Heart Failure Providers.

    Science.gov (United States)

    Doorenbos, Ardith Z; Levy, Wayne C; Curtis, J Randall; Dougherty, Cynthia M

    2016-09-01

    Heart failure patients contend with a markedly impaired quality of life, experiencing emotional distress and severe physical discomfort that increases in frequency in the last months of life. Improving communication between patients and providers about goals of care has the potential to improve patient-provider communication and patient outcomes. To determine the effects of a goals-of-care (GoC) intervention compared to usual care on the number of GoC conversations, quality of communication between patients and providers, referrals to palliative care services and completion of advance care directives. A two-group randomized study (n = 40/group) compared a GoC intervention to usual care, conducted in an academic heart failure (HF) clinic. The GoC intervention was a previsit patient activation-education, telephone-based intervention delivered by a nurse. The primary outcome of the study was number of GoC conversations between HF patients and HF providers. Secondary outcomes were quality of communication, number of referrals to palliative care, and completion of advance directives. Patients averaged 58.15 ± 11.26 years of age, with mean left ventricular ejection fraction = 30.31 ± 9.72% and Seattle Heart Failure Model scores = 95.1 ± 1.60. There was a significant increase in goals-of-care conversations (58% vs. 2.6%, P communication (P = 0.03) in the GoC group compared to usual care after the intervention. There were no differences between groups on the other outcomes. The GoC intervention resulted in more GoC conversations and higher quality communication between HF patients and providers without increased anxiety or depression. Further studies are needed to assess impact on longer term quality of care and patient outcomes. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  18. A human pericardium biopolymeric scaffold for autologous heart valve tissue engineering: cellular and extracellular matrix structure and biomechanical properties in comparison with a normal aortic heart valve.

    Science.gov (United States)

    Straka, Frantisek; Schornik, David; Masin, Jaroslav; Filova, Elena; Mirejovsky, Tomas; Burdikova, Zuzana; Svindrych, Zdenek; Chlup, Hynek; Horny, Lukas; Daniel, Matej; Machac, Jiri; Skibová, Jelena; Pirk, Jan; Bacakova, Lucie

    2018-04-01

    The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.

  19. Maximal heart rate does not limit cardiovascular capacity in healthy humans

    DEFF Research Database (Denmark)

    Munch, G D W; Svendsen, J H; Damsgaard, R

    2014-01-01

    In humans, maximal aerobic power (VO2 max ) is associated with a plateau in cardiac output (Q), but the mechanisms regulating the interplay between maximal heart rate (HRmax) and stroke volume (SV) are unclear. To evaluate the effect of tachycardia and elevations in HRmax on cardiovascular function...... and capacity during maximal exercise in healthy humans, 12 young male cyclists performed incremental cycling and one-legged knee-extensor exercise (KEE) to exhaustion with and without right atrial pacing to increase HR. During control cycling, Q and leg blood flow increased up to 85% of maximal workload (WLmax...... and RAP (P healthy...

  20. Transmural expression of ion channels and transporters in human nondiseased and end-stage failing hearts

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Olesen, Søren-Peter; Christ, Torsten

    2009-01-01

    The cardiac action potential is primarily shaped by the orchestrated function of several different types of ion channels and transporters. One of the regional differences believed to play a major role in the progression and stability of the action potential is the transmural gradient of electrica...... cardiac ion channels and transporters which may in part explain the increased susceptibility to arrhythmia in end-state failing hearts....... activity across the ventricular wall. An altered balance in the ionic currents across the free wall is assumed to be a substrate for arrhythmia. A large fraction of patients with heart failure experience ventricular arrhythmia. However, the underlying substrate of these functional changes is not well......-established as expression analyses of human heart failure (HF) are sparse. We have investigated steady-state RNA levels by quantitative polymerase chain reaction of ion channels, transporters, connexin 43, and miR-1 in 11 end-stage HF and seven nonfailing (NF) hearts. The quantifications were performed on endo-, mid...

  1. Impact of space weather on human heart rate during the years 2011-2013

    Science.gov (United States)

    Galata, E.; Ioannidou, S.; Papailiou, M.; Mavromichalaki, H.; Paravolidakis, K.; Kouremeti, M.; Rentifis, L.; Simantirakis, E.; Trachanas, K.

    2017-08-01

    During the last years a possible link between different levels of solar and geomagnetic disturbances and human physiological parameters is suggested by several published studies. In this work the examination of the potential association between heart rate variations and specific space weather activities was performed. A total of 482 individuals treated at Hippocratio General Hospital in Athens, the Cardiology clinics of Nikaia General Hospital in Piraeus and the Heraklion University Hospital in Crete, Greece, were assessed from July 2011 to April 2013. The heart rate of the individuals was recorded by a Holter monitor on a n hourly basis, while the hourly variations of the cosmic ray intensity measured by the Neutron Monitor Station of the Athens University and of the geomagnetic index Dst provided by the Kyoto Observatory were used. The ANalysis Of VAriance (ANOVA) and the Multiple Linear Regression analysis were used for analysis of these data. A statistically significant effect of both cosmic rays and geomagnetic activity on heart rate was observed, which may indicate that changes in space weather could be linked to heart rate variations.

  2. Electronic human resource management: Enhancing or entrancing?

    Directory of Open Access Journals (Sweden)

    Paul Poisat

    2017-07-01

    Full Text Available Orientation: This article provides an investigation into the current level of development of the body of knowledge related to electronic human resource management (e-HRM by means of a qualitative content analysis. Several aspects of e-HRM, namely definitions of e-HRM, the theoretical perspectives around e-HRM, the role of e-HRM, the various types of e-HRM and the requirements for successful e-HRM, are examined. Research purpose: The purpose of the article was to determine the status of e-HRM and examine the studies that report on the link between e-HRM and organisational productivity. Motivation for the study: e-HRM has the capacity to improve organisational efficiency and leverage the role of human resources (HR as a strategic business partner. Main findings: The notion that the implementation of e-HRM will lead to improved organisational productivity is commonly assumed; however, empirical evidence in this regard was found to be limited. Practical/managerial implications: From the results of this investigation it is evident that more research is required to gain a greater understanding of the influence of e-HRM on organisational productivity, as well as to develop measures for assessing this influence. Contribution: This article proposes additional areas to research and measure when investigating the effectiveness of e-HRM. It provides a different lens from which to view e-HRM assessment whilst keeping it within recognised HR measurement parameters (the HR value chain. In addition, it not only provides areas for measuring e-HRM’s influence but also provides important clues as to how the measurements may be approached.

  3. Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types.

    Science.gov (United States)

    Loh, Kyle M; Chen, Angela; Koh, Pang Wei; Deng, Tianda Z; Sinha, Rahul; Tsai, Jonathan M; Barkal, Amira A; Shen, Kimberle Y; Jain, Rajan; Morganti, Rachel M; Shyh-Chang, Ng; Fernhoff, Nathaniel B; George, Benson M; Wernig, Gerlinde; Salomon, Rachel E A; Chen, Zhenghao; Vogel, Hannes; Epstein, Jonathan A; Kundaje, Anshul; Talbot, William S; Beachy, Philip A; Ang, Lay Teng; Weissman, Irving L

    2016-07-14

    Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation toward unwanted fates and rapidly steer pluripotent stem cells toward 80%-99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously unobservable human embryonic event transiently marked by HOPX expression. Collectively, this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

    Science.gov (United States)

    Richards, Dylan J; Coyle, Robert C; Tan, Yu; Jia, Jia; Wong, Kerri; Toomer, Katelynn; Menick, Donald R; Mei, Ying

    2017-10-01

    Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology.

    Directory of Open Access Journals (Sweden)

    Sebastian Schaaf

    Full Text Available Human embryonic stem cell (hESC progenies hold great promise as surrogates for human primary cells, particularly if the latter are not available as in the case of cardiomyocytes. However, high content experimental platforms are lacking that allow the function of hESC-derived cardiomyocytes to be studied under relatively physiological and standardized conditions. Here we describe a simple and robust protocol for the generation of fibrin-based human engineered heart tissue (hEHT in a 24-well format using an unselected population of differentiated human embryonic stem cells containing 30-40% α-actinin-positive cardiac myocytes. Human EHTs started to show coherent contractions 5-10 days after casting, reached regular (mean 0.5 Hz and strong (mean 100 µN contractions for up to 8 weeks. They displayed a dense network of longitudinally oriented, interconnected and cross-striated cardiomyocytes. Spontaneous hEHT contractions were analyzed by automated video-optical recording and showed chronotropic responses to calcium and the β-adrenergic agonist isoprenaline. The proarrhythmic compounds E-4031, quinidine, procainamide, cisapride, and sertindole exerted robust, concentration-dependent and reversible decreases in relaxation velocity and irregular beating at concentrations that recapitulate findings in hERG channel assays. In conclusion this study establishes hEHT as a simple in vitro model for heart research.

  6. Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E.; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Liao, Mei-Ling Chang; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D.; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W.; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A.; Unger, Andreas; Linke, Wolfgang A.; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C.; Zimmermann, Wolfram-Hubertus

    2017-01-01

    Background Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. Methods We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We employed morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M-bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency-response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release; all are classical hallmarks of heart failure. Additionally, we demonstrate scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions We provide proof-of-concept for a universally applicable technology for the engineering of macro-scale human myocardium for disease modelling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. PMID:28167635

  7. Analysis of Ion Currents Contribution to Repolarization in Human Heart Failure Using Computer Models

    Energy Technology Data Exchange (ETDEWEB)

    Marotta, F.; Paci, M.A.; Severi, S.; Trenor, B.

    2016-07-01

    The mechanisms underlying repolarization of the ventricular action potential (AP) are subject of research for anti-arrhythmic drugs. In fact, the prolongation of the AP occurs in several conditions of heart disease, such as heart failure, a major problem precursor for serious arrhythmias. In this study, we investigated the phenomena of repolarization reserve, defined as the capacity of the cell to repolarize in case of a functional loss, and the all-or-none repolarization, which depends on the delicate balance of inward and outward currents in the different phases of the AP, under conditions of human heart failure (HF). To simulate HF conditions, the O'Hara et al. human AP model was modified and specific protocols for all-or-none repolarization were applied. Our results show that in the early repolarization the threshold for all-or-none repolarization is not altered in HF even if a decrease in potassium currents can be observed. To quantify the contribution of the individual ion currents to HF induced AP prolongation, we used a novel piecewise-linear approximation approach proposed by Paci et al. In particular, INaL and ICaL are the main responsible for APD prolongation due to HF (85 and 35 ms respectively). Our results highlight this novel algorithm as a powerful tool to have a more complete picture of the complex ionic mechanisms underlying this disease and confirm the important role of the late sodium current in HF repolarization. (Author)

  8. Concentration of 24 Trace Elements in Human Heart Tissue Determined by Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wester, P O

    1964-06-15

    By means of neutron-activation analysis, human heart tissue from autopsy of 20 victims of traumatic accidents has been investigated with respect to the concentration of 24 different trace elements. A recently developed ion-exchange technique combined with gamma spectrometry has been used, which permits simultaneous determination of a large number of trace elements. The following trace elements have been determined quantitatively: Ag, As, Au, Ba, Br; Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Pt, Rb, Sb, Se, Se, Sm, Zn, W. In some heart samples, Hf and Os were determined qualitatively. The mean and standard deviation are given for the elements Cu, Fe, Se and Zn, Since none of the other quantitatively determined trace elements were normally distributed, the median is given as the central value. When possible, comparisons with values from other investigations have been made. No marked differences in the trace-element concentrations with age or sex could be detected.

  9. Combined use of autogenic therapy and biofeedback in training effective control of heart rate by humans

    Science.gov (United States)

    Cowings, P. S.

    1977-01-01

    Experiments were performed on 24 men and women (aged 20-27 yr) in three equal groups who were taught to control their own heart rates by autogenic training and biofeedback under dark and sound-isolated conditions. Group I was parasympathetic dominant, group II was sympathetic dominant, and group III consisted of parasympathetic-dominant subjects and controls who received only biofeedback of their own heart rates. The results corroborate three hypotheses: (1) subjects with para-sympathetic-dominant autonomic profiles perform in a way that is both qualitatively and quantitatively different from subjects with sympathetic-dominant autonomic profiles; (2) tests of interindividual variability yield data relevant to individual performance in visceral learning tasks; and (3) the combined use of autogenic training, biofeedback, and verbal feedback is suitable for conditioning large stable autonomic responses in humans.

  10. Concentration of 24 Trace Elements in Human Heart Tissue Determined by Neutron Activation Analysis

    International Nuclear Information System (INIS)

    Wester, P.O.

    1964-06-01

    By means of neutron-activation analysis, human heart tissue from autopsy of 20 victims of traumatic accidents has been investigated with respect to the concentration of 24 different trace elements. A recently developed ion-exchange technique combined with gamma spectrometry has been used, which permits simultaneous determination of a large number of trace elements. The following trace elements have been determined quantitatively: Ag, As, Au, Ba, Br; Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Pt, Rb, Sb, Se, Se, Sm, Zn, W. In some heart samples, Hf and Os were determined qualitatively. The mean and standard deviation are given for the elements Cu, Fe, Se and Zn, Since none of the other quantitatively determined trace elements were normally distributed, the median is given as the central value. When possible, comparisons with values from other investigations have been made. No marked differences in the trace-element concentrations with age or sex could be detected

  11. Kernel Method Based Human Model for Enhancing Interactive Evolutionary Optimization

    Science.gov (United States)

    Zhao, Qiangfu; Liu, Yong

    2015-01-01

    A fitness landscape presents the relationship between individual and its reproductive success in evolutionary computation (EC). However, discrete and approximate landscape in an original search space may not support enough and accurate information for EC search, especially in interactive EC (IEC). The fitness landscape of human subjective evaluation in IEC is very difficult and impossible to model, even with a hypothesis of what its definition might be. In this paper, we propose a method to establish a human model in projected high dimensional search space by kernel classification for enhancing IEC search. Because bivalent logic is a simplest perceptual paradigm, the human model is established by considering this paradigm principle. In feature space, we design a linear classifier as a human model to obtain user preference knowledge, which cannot be supported linearly in original discrete search space. The human model is established by this method for predicting potential perceptual knowledge of human. With the human model, we design an evolution control method to enhance IEC search. From experimental evaluation results with a pseudo-IEC user, our proposed model and method can enhance IEC search significantly. PMID:25879050

  12. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography

    International Nuclear Information System (INIS)

    Schwaiger, M.; Kalff, V.; Rosenspire, K.; Haka, M.S.; Molina, E.; Hutchins, G.D.; Deeb, M.; Wolfe, E. Jr.; Wieland, D.M.

    1990-01-01

    The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial [11C]hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, [11C]hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart

  13. Human Resource Management in the Enhancement Processes of Knowledge Management

    Directory of Open Access Journals (Sweden)

    Didi Sundiman

    2017-11-01

    Full Text Available This research explored Human Resource Management (HRM in enhancement processes of knowledge management. This research explored how HRM practice enhanced the operational of knowledge management. Data were collected by a survey by interviewing 12 informants from Small and Medium Enterprise (SME. The results show that HRM practice gives initiative in the enhancement process of the knowledge management strategy applied to the company. It can be concluded that each sub-component of HRM affects the components of knowledge management, and HRM is highly influential and has a positive effect on quality management processes and vice versa in the work environment.

  14. [Human nature and the enhancement of human beings in the light of the transhumanist program].

    Science.gov (United States)

    Goffi, Jean-Yves

    2011-01-01

    There are three main approaches about the question of Human Nature. essentialists consider that there exists a permanent Human Nature, shared by every human being. Existentialists consider that there is no such thing as human nature, but inescapable modes of being in the world. A moderate approach would consider that Human Nature can be modified within the limits of anthropological invariants. Transhumanists are conservative in that they think that there is a Human Nature; but they are radical in that they believe that it can (and must) be transcended by bio-technnologies and computer technologies. This project is evaluated as a caricature of suitable human enhancement.

  15. Nkx2.5 enhances the efficacy of mesenchymal stem cells transplantation in treatment heart failure in rats.

    Science.gov (United States)

    Deng, Bo; Wang, Jin Xin; Hu, Xing Xing; Duan, Peng; Wang, Lin; Li, Yang; Zhu, Qing Lei

    2017-08-01

    The aim of this study is to determine whether Nkx2.5 transfection of transplanted bone marrow mesenchymal stem cells (MSCs) improves the efficacy of treatment of adriamycin-induced heart failure in a rat model. Nkx2.5 was transfected in MSCs by lentiviral vector transduction. The expressions of Nkx2.5 and cardiac specific genes in MSCs and Nkx2.5 transfected mesenchymal stem cells (MSCs-Nkx2.5) were analyzed with quantitative real-time PCR and Western blot in vitro. Heart failure models of rats were induced by adriamycin and were then randomly divided into 3 groups: injected saline, MSCs or MSCs-Nkx2.5 via the femoral vein respectively. Four weeks after injection, the cardiac function, expressions of cardiac specific gene, fibrosis formation and collagen volume fraction in the myocardium as well as the expressions of GATA4 and MEF2 in rats were analyzed with echocardiography, immunohistochemistry, Masson staining, quantitative real-time PCR and Western blot, respectively. Nkx2.5 enhanced cardiac specific gene expressions including α-MHC, TNI, CKMB, connexin-43 in MSCs-Nkx2.5 in vitro. Both MSCs and MSCs-Nkx2.5 improved cardiac function, promoted the differentiation of transplanted MSCs into cardiomyocyte-like cells, decreased fibrosis formation and collagen volume fraction in the myocardium, as well as increased the expressions of GATA4 and MEF2 in adriamycin-induced rat heart failure models. Moreover, the effect was much more remarkable in MSCs-Nkx2.5 than in MSCs group. This study has found that Nkx2.5 enhances the efficacy of MSCs transplantation in treatment adriamycin-induced heart failure in rats. Nkx2.5 transfected to transplanted MSCs provides a potential effective approach to heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. CD133 antibody conjugation to decellularized human heart valves intended for circulating cell capture.

    Science.gov (United States)

    Vossler, John D; Min Ju, Young; Williams, J Koudy; Goldstein, Steven; Hamlin, James; Lee, Sang Jin; Yoo, James J; Atala, Anthony

    2015-09-03

    The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases.

  17. Plants and Human Affairs: Educational Enhancement Via a Computer.

    Science.gov (United States)

    Crovello, Theodore J.; Smith, W. Nelson

    To enhance both teaching and learning in an advanced undergraduate elective course on the interrelationships of plants and human affairs, the computer was used for information retrieval, multiple choice course review, and the running of three simulation models--plant related systems (e.g., the rise in world coffee prices after the 1975 freeze in…

  18. Enhancing Biology Instruction with the Human Genome Project

    Science.gov (United States)

    Buxeda, Rosa J.; Moore-Russo, Deborah A.

    2003-01-01

    The Human Genome Project (HGP) is a recent scientific milestone that has received notable attention. This article shows how a biology course is using the HGP to enhance students' experiences by providing awareness of cutting edge research, with information on new emerging career options, and with opportunities to consider ethical questions raised…

  19. Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*

    Science.gov (United States)

    Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.

    2013-01-01

    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

  20. National plan to enhance aviation safety through human factors improvements

    Science.gov (United States)

    Foushee, Clay

    1990-01-01

    The purpose of this section of the plan is to establish a development and implementation strategy plan for improving safety and efficiency in the Air Traffic Control (ATC) system. These improvements will be achieved through the proper applications of human factors considerations to the present and future systems. The program will have four basic goals: (1) prepare for the future system through proper hiring and training; (2) develop a controller work station team concept (managing human errors); (3) understand and address the human factors implications of negative system results; and (4) define the proper division of responsibilities and interactions between the human and the machine in ATC systems. This plan addresses six program elements which together address the overall purpose. The six program elements are: (1) determine principles of human-centered automation that will enhance aviation safety and the efficiency of the air traffic controller; (2) provide new and/or enhanced methods and techniques to measure, assess, and improve human performance in the ATC environment; (3) determine system needs and methods for information transfer between and within controller teams and between controller teams and the cockpit; (4) determine how new controller work station technology can optimally be applied and integrated to enhance safety and efficiency; (5) assess training needs and develop improved techniques and strategies for selection, training, and evaluation of controllers; and (6) develop standards, methods, and procedures for the certification and validation of human engineering in the design, testing, and implementation of any hardware or software system element which affects information flow to or from the human.

  1. Polonium 210Po activities in human blood of patients with ischaemic heart disease from Gda?sk in Poland

    OpenAIRE

    Bory?o, Alicja; Skwarzec, Bogdan; Roma?czyk, Grzegorz; Siebert, Janusz

    2013-01-01

    The determination of polonium 210Po in human blood samples is presented and discussed in this paper. The human blood samples were collected from patients of Medical University of Gda?sk with ischaemic heart disease (morbus ischaemicus cordis, MIC). The polonium concentrations in analyzed human blood samples are very differentiated. 210Po is of particular interest in public health and although is present in the environment in extremely low amounts, it is easily bioaccumulated to the human body...

  2. Rewiring food systems to enhance human health and biosphere stewardship

    Science.gov (United States)

    Gordon, Line J.; Bignet, Victoria; Crona, Beatrice; Henriksson, Patrik J. G.; Van Holt, Tracy; Jonell, Malin; Lindahl, Therese; Troell, Max; Barthel, Stephan; Deutsch, Lisa; Folke, Carl; Jamila Haider, L.; Rockström, Johan; Queiroz, Cibele

    2017-10-01

    Food lies at the heart of both health and sustainability challenges. We use a social-ecological framework to illustrate how major changes to the volume, nutrition and safety of food systems between 1961 and today impact health and sustainability. These changes have almost halved undernutrition while doubling the proportion who are overweight. They have also resulted in reduced resilience of the biosphere, pushing four out of six analysed planetary boundaries across the safe operating space of the biosphere. Our analysis further illustrates that consumers and producers have become more distant from one another, with substantial power consolidated within a small group of key actors. Solutions include a shift from a volume-focused production system to focus on quality, nutrition, resource use efficiency, and reduced antimicrobial use. To achieve this, we need to rewire food systems in ways that enhance transparency between producers and consumers, mobilize key actors to become biosphere stewards, and re-connect people to the biosphere.

  3. Enhancing prescribing of guideline-recommended medications for ischaemic heart diseases: a systematic review and meta-analysis of interventions targeted at healthcare professionals

    NARCIS (Netherlands)

    Nguyen, Thang; Nguyen, Hoa Q; Widyakusuma, Niken N; Nguyen, Thao H; Pham, Tam T; Taxis, Katja

    Objectives Ischaemic heart diseases (IHDs) are a leading cause of death worldwide. Although prescribing according to guidelines improves health outcomes, it remains suboptimal. We determined whether interventions targeted at healthcare professionals are effective to enhance prescribing and health

  4. Heart regeneration.

    Science.gov (United States)

    Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

    2016-07-01

    Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Analysis of cardiac myosin binding protein-C phosphorylation in human heart muscle.

    Science.gov (United States)

    Copeland, O'Neal; Sadayappan, Sakthivel; Messer, Andrew E; Steinen, Ger J M; van der Velden, Jolanda; Marston, Steven B

    2010-12-01

    A unique feature of MyBP-C in cardiac muscle is that it has multiple phosphorylation sites. MyBP-C phosphorylation, predominantly by PKA, plays an essential role in modulating contractility as part of the cellular response to β-adrenergic stimulation. In vitro studies indicate MyBP-C can be phosphorylated at Serine 273, 282, 302 and 307 (mouse sequence) but little is known about the level of MyBP-C phosphorylation or the sites phosphorylated in heart muscle. Since current methodologies are limited in specificity and are not quantitative we have investigated the use of phosphate affinity SDS-PAGE together with a total anti MyBP-C antibody and a range of phosphorylation site-specific antibodies for the main sites (Ser-273, -282 and -302). With these newly developed methods we have been able to make a detailed quantitative analysis of MyBP-C phosphorylation in heart tissue in situ. We have found that MyBP-C is highly phosphorylated in non-failing human (donor) heart or mouse heart; tris and tetra-phosphorylated species predominate and less than 10% of MyBP-C is unphosphorylated (0, 9.3 ± 1%: 1P, 13.4 ± 2.7%: 2P, 10.5 ± 3.3%: 3P, 28.7 ± 3.7%: 4P, 36.4 ± 2.7%, n=21). Total phosphorylation was 2.7 ± 0.07 mol Pi/mol MyBP-C. In contrast in failing heart and in myectomy samples from HCM patients the majority of MyBP-C was unphosphorylated. Total phosphorylation levels were 23% of normal in failing heart myofibrils (0, 60.1 ± 2.8%: 1P, 27.8 ± 2.8%: 2P, 4.8 ± 2.0%: 3P, 3.7 ± 1.2%: 4P, 2.8 ± 1.3%, n=19) and 39% of normal in myectomy samples. The site-specific antibodies showed a distinctive distribution pattern of phosphorylation sites in the multiple phosphorylation level species. We found that phosphorylated Ser-273, Ser-282 and Ser-302 were all present in the 4P band of MyBP-C but none of them were significant in the 1P band, indicating that there must be at least one other site of MyBP-C phosphorylation in human heart. The pattern of phosphorylation at the

  6. Application of low dose radiation and low concentration contrast media in enhanced CT scans in children with congenital heart disease.

    Science.gov (United States)

    Liu, Zhimin; Song, Lei; Yu, Tong; Gao, Jun; Zhang, Qifeng; Jiang, Ling; Liu, Yong; Peng, Yun

    2016-09-01

    The aim of this study was to explore the feasibility of using low dose radiation and low concentration contrast media in enhanced CT examinations in children with congenital heart disease. Ninety patients with congenital heart disease were randomly divided into three groups of 30 patients each who underwent contrast-enhanced cardiac scans on a Discovery CT750 HD scanner. Group A received 270 mg I/mL iodixanol, and group B received 320 mg I/mL iodixanol contrast media and was scanned with prospective ECG triggering mode. Group C received 320 mg I/mL iodixanol and was scanned with conventional retrospective ECG gating mode. The same weight-based contrast injection protocol was used for all three groups. Images were reconstructed using a 30% adaptive statistical iterative reconstruction (ASIR) algorithm and a 50% ASIR in groups A and B and a 30% ASIR in group C. The subjective and objective image quality evaluations, diagnostic accuracies, radiation doses and amounts of contrast media in the three groups were measured and compared. All images in the three groups met the diagnostic requirements, with the same diagnostic accuracy and image quality scores greater than 3 in a 4-point scoring system. However, ventricular enhancement and the objective noise, signal-to-noise ratio, contrast-to-noise ratio and subjective image quality scores in group C were better than those in groups A and B (all Pcontrast dose (14% lower than that of groups B and C). Enhanced CT scan images with low dose radiation and low concentration contrast media can meet the diagnostic requirements for examining children with congenital heart disease while reducing the potential risk of radiation damage and contrast-induced nephropathy. © 2016 John Wiley & Sons Ltd.

  7. Enhancement by platelets of oxygen radical responses of human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

    1986-03-01

    When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O-/sub 2/ and H/sub 2/O/sub 2/. This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O-/sub 2/ generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O-/sub 2/ responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils.

  8. Enhancement by platelets of oxygen radical responses of human neutrophils

    International Nuclear Information System (INIS)

    McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

    1986-01-01

    When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O- 2 and H 2 O 2 . This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O- 2 generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O- 2 responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils

  9. Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation.

    Science.gov (United States)

    Meyer-Roxlau, Stefanie; Lämmle, Simon; Opitz, Annett; Künzel, Stephan; Joos, Julius P; Neef, Stefan; Sekeres, Karolina; Sossalla, Samuel; Schöndube, Friedrich; Alexiou, Konstantin; Maier, Lars S; Dobrev, Dobromir; Guan, Kaomei; Weber, Silvio; El-Armouche, Ali

    2017-07-01

    Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms α and γ but unaltered PP1β levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1α abundance and activity, as indicated by higher phosphorylation of the PP1α-specific substrate eIF2α. Greater eIF2α phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1α activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.

  10. Applying lessons learned to enhance human performance and reduce human error for ISS operations

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, W.R.

    1998-09-01

    A major component of reliability, safety, and mission success for space missions is ensuring that the humans involved (flight crew, ground crew, mission control, etc.) perform their tasks and functions as required. This includes compliance with training and procedures during normal conditions, and successful compensation when malfunctions or unexpected conditions occur. A very significant issue that affects human performance in space flight is human error. Human errors can invalidate carefully designed equipment and procedures. If certain errors combine with equipment failures or design flaws, mission failure or loss of life can occur. The control of human error during operation of the International Space Station (ISS) will be critical to the overall success of the program. As experience from Mir operations has shown, human performance plays a vital role in the success or failure of long duration space missions. The Department of Energy`s Idaho National Engineering and Environmental Laboratory (INEEL) is developed a systematic approach to enhance human performance and reduce human errors for ISS operations. This approach is based on the systematic identification and evaluation of lessons learned from past space missions such as Mir to enhance the design and operation of ISS. This paper describes previous INEEL research on human error sponsored by NASA and how it can be applied to enhance human reliability for ISS.

  11. Staying human in the 21st century : thinking beyond human enhancement technologies inside the body

    NARCIS (Netherlands)

    Est, van Q.C.; Schuijff, M.; Boer, de T.; Fischer, R.

    2013-01-01

    The debate on human enhancement has focused so far on invasive biomedical technologies that work inside the body. To fully address the question of what does it mean to be human in the 21st century, we should also pay attention to a broad range of technologies that work outside the body, but still

  12. In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts

    Directory of Open Access Journals (Sweden)

    F Di Meglio

    2009-08-01

    Full Text Available The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR. The amount of proteins characteristic for cardiac cells (a-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively inclines toward an increase in both a-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart.

  13. Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure.

    Science.gov (United States)

    Meana, Clara; Rubín, José Manuel; Bordallo, Carmen; Suárez, Lorena; Bordallo, Javier; Sánchez, Manuel

    2016-02-01

    Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N(1)-acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO-N(1) -acetylspermine (r = -0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N(1)-acetylspermidine (r = -0.554, P = 0.032; r = -0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = -0.835, P = 0.001) and with cAMP/ODC (r = -0.794, P = 0.011), cAMP/spermidine (r = -0.813, P = 0.001) and cAMP/spermine (r = -0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N(1) -acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = -0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of

  14. Ethacrynic acid: a novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Khil, Mark S.; Sang, Hie Kim; Pinto, John T.; Jae, Ho Kim

    1996-01-01

    Purpose: Because agents that interfere with thiol metabolism and glutathione S-transferase (GST) functions have been shown to enhance antitumor effects of alkylating agents in vitro and in vivo, the present study was conceived on the basis that an inhibitor of GST would enhance the radiation response of some selected human carcinoma cells. Ethacrynic acid (EA) was chosen for the study because it is an effective inhibitor of GST and is a well known diuretic in humans. Methods and Materials: Experiments were carried out with well-established human tumor cells in culture growing in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum (FCS). Cell lines used were MCF-7, MCF-7 adriamycin resistant (AR) cells (breast carcinoma), HT-29 cells (colon carcinoma), DU-145 cells (prostate carcinoma), and U-373 cells (malignant glioma). Cell survival following the exposure of cells to drug alone, radiation alone, and a combined treatment was assayed by determining the colony-forming ability of single plated cells in culture to obtain dose-survival curves. The drug enhancement ratio was correlated with levels of GST. Results: The cytotoxicity of EA was most pronounced in MCF-7, U-373, and DU-145 cells compared to MCF-7 AR and HT-29 cells. The levels of GST activity were found to be lower in those EA-sensitive cells. A significant radiation enhancement was obtained with EA-sensitive cells exposed to nontoxic concentrations of the drug immediately before or after irradiation. The sensitizer enhancement ratio (SER) of MCF-7 cells was 1.55 with EA (20 μg/ml), while the SER of MCF-7 AR was less than 1.1. Based on five different human tumor cells, a clear inverse relationship was demonstrated between the magnitude of SER and GST levels of tumor cells prior to the combined treatment. Conclusion: The present results suggest that EA, which acts as both a reversible and irreversible inhibitor of GST activity, could significantly enhance the radiation response of

  15. Human care system for heart-rate and human-movement trajectory in home and its application to detect mental disease

    Science.gov (United States)

    Hata, Yutaka; Kanazawa, Seigo; Endo, Maki; Tsuchiya, Naoki; Nakajima, Hiroshi

    2012-06-01

    This paper proposes a heart rate monitoring system for detecting autonomic nervous system by the heart rate variability using an air pressure sensor to diagnose mental disease. Moreover, we propose a human behavior monitoring system for detecting the human trajectory in home by an infrared camera. In day and night times, the human behavior monitoring system detects the human movement in home. The heart rate monitoring system detects the heart rate in bed in night time. The air pressure sensor consists of a rubber tube, cushion cover and pressure sensor, and it detects the heart rate by setting it to bed. It unconstraintly detects the RR-intervals; thereby the autonomic nervous system can be assessed. The autonomic nervous system analysis can examine the mental disease. While, the human behavior monitoring system obtains distance distribution image by an infrared camera. It classifies adult, child and the other object from distance distribution obtained by the camera, and records their trajectories. This behavior, i.e., trajectory in home, strongly corresponds to cognitive disorders. Thus, the total system can detect mental disease and cognitive disorders by uncontacted sensors to human body.

  16. Radiation enhanced reactivation of irradiated human adenovirus type 2 in human cells

    International Nuclear Information System (INIS)

    Jeeves, W.P.

    1981-04-01

    Radiation-enhanced reactivation (ER) of a radiation-damaged mammalian virus is the term given to the observation that the survival of irradiated virus can be enhanced by irradiation of an appropriate host cell prior to infection. In this work, both UV-enhanced reactivation (UVER) and gamma-ray-enhanced reactivation (γRER) of irradiated human adenovirus type 2 (AD 2) were studied in a variety of normal and DNA repair-deficient human fibroblast host cell strains. In order to examine the lesion specificity of ER in human cells, experiments were performed using UV-irradiated and γ-irradiated virus. The investigation was carried out using a sensitive technique of indirect immunofluorescence, according to which irradiated and unirradiated cell cultures were infected with irradiated or unirradiated AD 2 and were subsequently examined for the presence of viral structural antigens ('V' Ag) at a fixed time after infection

  17. Cardiac re-entry dynamics and self-termination in DT-MRI based model of Human Foetal Heart

    Science.gov (United States)

    Biktasheva, Irina V.; Anderson, Richard A.; Holden, Arun V.; Pervolaraki, Eleftheria; Wen, Fen Cai

    2018-02-01

    The effect of human foetal heart geometry and anisotropy on anatomy induced drift and self-termination of cardiac re-entry is studied here in MRI based 2D slice and 3D whole heart computer simulations. Isotropic and anisotropic models of 20 weeks of gestational age human foetal heart obtained from 100μm voxel diffusion tensor MRI data sets were used in the computer simulations. The fiber orientation angles of the heart were obtained from the orientation of the DT-MRI primary eigenvectors. In a spatially homogeneous electrophysiological monodomain model with the DT-MRI based heart geometries, cardiac re-entry was initiated at a prescribed location in a 2D slice, and in the 3D whole heart anatomy models. Excitation was described by simplified FitzHugh-Nagumo kinetics. In a slice of the heart, with propagation velocity twice as fast along the fibres than across the fibers, DT-MRI based fiber anisotropy changes the re-entry dynamics from pinned to an anatomical re-entry. In the 3D whole heart models, the fiber anisotropy changes cardiac re-entry dynamics from a persistent re-entry to the re-entry self-termination. The self-termination time depends on the re-entry’s initial position. In all the simulations with the DT-MRI based cardiac geometry, the anisotropy of the myocardial tissue shortens the time to re-entry self-termination several folds. The numerical simulations depend on the validity of the DT-MRI data set used. The ventricular wall showed the characteristic transmural rotation of the helix angle of the developed mammalian heart, while the fiber orientation in the atria was irregular.

  18. Predicting Tissue-Specific Enhancers in the Human Genome

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  19. Mechanisms for training security inspectors to enhance human performance

    International Nuclear Information System (INIS)

    Burkhalter, H.E.; Sessions, J.C.

    1988-01-01

    The Department of Energy (DOE) has established qualification standards for protective force personnel employed at nuclear facilities [10 CFR Part 1046 (Federal Register)]. Training mechanisms used at Los Alamos to enhance human performance in meeting DOE standards include, but are not limited to, the following: for cardio-respiratory training, they utilize distance running, interval training, sprint training, pacing, indoor aerobics and circuit training; for muscular strength, free weights, weight machines, light hand weights, grip strength conditioners, and calistenics are employed; for muscular endurance, participants do high repetitions (15 - 40) using dumbbells, flex weights, resistive rubber bands, benches, and calisthenics; for flexibility, each training session devotes specific times to stretch the muscles involved for a particular activity. These training mechanisms with specific protocols can enhance human performance

  20. Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

    Directory of Open Access Journals (Sweden)

    Linn S Strandberg

    Full Text Available Congenital heart block (CHB is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation. Using human fetal hearts (20-22 wks gestation, our immunoprecipitation (IP, Western blot analysis and immunofluorescence (IF staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I. Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN cells.Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

  1. Protective effects of recombinant human brain natriuretic peptide in perioperative period during open heart surgery.

    Science.gov (United States)

    Xu, Yunbin; Li, Yong; Bao, Weiguo; Qiu, Shi

    2018-03-01

    The aim of the present study was to evaluate the protective effects and safety aspects of recombinant human brain natriuretic peptide (rhBNP) on cardiac functions of patients undergoing open-heart surgery during perioperative period. In total, 150 patients undergoing open heart surgery in the Second Hospital of Shandong Universty from August 2015 to July 2016 were randomly divided into control group and observation group each with 75 cases. Patients in control group were treated by routine rehabilitation while patients in the observation group were treated by both the routine rehabilitation and rhBNP. All the observations were made before operation, after operation and 7 days after operation. The changes of N-terminal pro-brain natriuretic peptide (NT-proBNP) of patients, the left ventricular ejection fraction (LVEF), cardiac function [Cardiac output (CO), pulmonary capillary wedge pressure (PAWP) and central venous pressure (CVP)] of patients were measured. Further, respirator support time, ICU stay time, incidence of complications and vital signs (BP, HR, SaO2) of patients in the two groups were also compared. NT-proBNP levels of all patients improved after operation but it decreased in both groups after 7 days of operation. The decrease of NT-proBNP levels in observation group was significantly higher than that of control group. Whereas, LVEF, CO, PAWP and CVP of patients in both the groups increased after operation but effects were significantly higher in the observation group after 7 days of medication. Respirator support time and ICU stay time of patients in observation group were significantly shorter than those in control group, and the incidence of postoperative complications of patients in the observation group were significantly lower than the control group. Moreover, BP, HR and SaO2 of patients in observation group were significantly elevated in comparison to control group (Popen heart surgery, and is safe as well as reliable.

  2. Human atrial natriuretic peptide treatment for acute heart failure: a systematic review of efficacy and mortality.

    Science.gov (United States)

    Kobayashi, Daiki; Yamaguchi, Norihiro; Takahashi, Osamu; Deshpande, Gautam A; Fukui, Tsuguya

    2012-01-01

    The objectives of this study were to assess the effect of human atrial natriuretic peptide (hANP) treatment on physiological parameters and mortality in acute heart failure. The MEDLINE (1966-2009), EMBASE (1980-2009), Cochrane Central Register of Controlled Trials (1991-2009), American College of Physicians Journal Club (1991), Ichushi (Japana Centra Revuo Medicina) (1983-2009), Cinni (NII Scholarly and Academic Information Navigator) (1959-2009), National Diet Library Online Public Access Catalog (1969-2009), Webcat Plus (Japanese National Institute of Informatics) (1986-2009), Medical Online (1947-2009), and JST China (1981-2009) databases were searched for studies that compared the efficacy of hANP and the mortality in patients with acute heart failure with placebo controls. Only randomized controlled trials (RCTs) were included in the study. Out of 347 articles, a total of 4 studies involving 220 patients with acute heart failure fulfilled the predefined inclusion criteria. There were significant differences in the hemodynamic parameters between the hANP and placebo groups, especially in the pulmonary capillary wedge pressure (PCWP) reduction (standard mean difference [SMD] 2.07; 95% confidence interval [CI], 0.34-3.81) and the cardiac index (SMD 1.79; 95% CI, 0.12-3.47). No statistically significant differences in mortality rates were found (relative risk 1.03; 95% CI, 0.27-3.92). In a limited number of studies, hANP appears to improve several hemodynamic parameters, including pulmonary capillary wedge pressure and cardiac index, but not mortality. Further high-quality studies are needed to corroborate these results. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  3. Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

    International Nuclear Information System (INIS)

    Mongillo, Marco; Leccisotti, Lucia; John, Anna S.; Pennell, Dudley J.; Camici, Paolo G.

    2007-01-01

    We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Eight patients (aged 67 ± 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 ± 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [ 11 C]meta-hydroxy-ephedrine (HED) volume of distribution (V d ) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 ± 4 years, p -1 .g -1 ) and dysfunctional (0.49 ± 0.14 μmol.min -1 .g -1 ) segments compared with controls (0.61 ± 0.7 μmol.min -1 .g -1 ; p d was reduced in dysfunctional segments of patients (38.9 ± 21.2 ml.g -1 ) compared with normal segments (52.2 ± 19.6 ml.g -1 ) and compared with controls (62.7 ± 11.3 ml.g -1 ). In patients, regional MGU was correlated with HED V d . The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. (orig.)

  4. Enhanced and updated American Heart Association heart-check front-of-package symbol: efforts to help consumers identify healthier food choices

    Science.gov (United States)

    A variety of nutrition symbols and rating systems are in use on the front of food packages. They are intended to help consumers make healthier food choices. One system, the American Heart Association Heart (AHA) Heart-Check Program, has evolved over time to incorporate current science-based recommen...

  5. Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support.

    Science.gov (United States)

    Yang, Kai-Chien; Yamada, Kathryn A; Patel, Akshar Y; Topkara, Veli K; George, Isaac; Cheema, Faisal H; Ewald, Gregory A; Mann, Douglas L; Nerbonne, Jeanne M

    2014-03-04

    Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD). Deep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that cis-gene regulation represents a major mechanism of action of human cardiac lncRNAs. The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.

  6. Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy

    Directory of Open Access Journals (Sweden)

    Olla Carlo

    2007-08-01

    Full Text Available Abstract Background The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21 genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microarrays we compared the gene expression profiles of hearts of human fetuses with and without Hsa21 trisomy. Results Approximately half of the 15,000 genes examined (87 of the 168 genes on Hsa21 were expressed in the heart at 18–22 weeks of gestation. Hsa21 gene expression was globally upregulated 1.5 fold in trisomic samples. However, not all genes were equally dysregulated and 25 genes were not upregulated at all. Genes located on other chromosomes were also significantly dysregulated. Functional class scoring and gene set enrichment analyses of 473 genes, differentially expressed between trisomic and non-trisomic hearts, revealed downregulation of genes encoding mitochondrial enzymes and upregulation of genes encoding extracellular matrix proteins. There were no significant differences between trisomic fetuses with and without heart defects. Conclusion We conclude that dosage-dependent upregulation of Hsa21 genes causes dysregulation of the genes responsible for mitochondrial function and for the extracellular matrix organization in the fetal heart of trisomic subjects. These alterations might be harbingers of the heart defects associated with Hsa21 trisomy, which could be based on elusive mechanisms involving genetic variability, environmental factors and/or stochastic events.

  7. Regenerating the human heart: direct reprogramming strategies and their current limitations.

    Science.gov (United States)

    Ghiroldi, Andrea; Piccoli, Marco; Ciconte, Giuseppe; Pappone, Carlo; Anastasia, Luigi

    2017-10-27

    Cardiovascular diseases are the leading cause of death in the Western world. Unfortunately, current therapies are often only palliative, consequently essentially making heart transplantation necessary for many patients. However, several novel therapeutic approaches in the past two decades have yielded quite encouraging results. The generation of induced pluripotent stem cells, through the forced expression of stem cell-specific transcription factors, has inspired the most promising strategies for heart regeneration by direct reprogramming of cardiac fibroblasts into functional cardiomyocytes. Initial attempts at this reprogramming were conducted using a similar approach to the one used with transcription factors, but during years, novel strategies have been tested, e.g., miRNAs, recombinant proteins and chemical molecules. Although preliminary results on animal models are promising, the low reprogramming efficiency, as well as the incomplete maturation of the cardiomyocytes, still represents important obstacles. This review covers direct transdifferentiation strategies that have been proposed and developed and illustrates the pros and cons of each approach. Indeed, as described in the manuscript, there are still many unanswered questions and drawbacks that require a better understanding of the basic signaling pathways and transcription factor networks before functional cells, suitable for cardiac regeneration and safe for the patients, can be generated and used for human therapies.

  8. Consciousness, mind and body : investigating Sartre's view on human being : "what lies at the heart of man?"

    OpenAIRE

    Karlsen, Lise Storm

    2008-01-01

    “What lies at the heart of human being?” That is the central theme of this paper. An investigation into human being can be approached in many ways. Mine is different than for instance psychology, anthropology, social science and biology. It is more in the direction of the metaphorically use of the expression “at the heart”: Having “her heart in it” (being committed, motivated, truly interested): Being a leader “with heart” (being generous, emphatic, accepting): A “heartfelt truth” (an intuiti...

  9. Artificial heart

    Energy Technology Data Exchange (ETDEWEB)

    1984-10-18

    Super-pure plutonium-238 could use heat produced during fission to power an implanted artificial heart. Three model hearts have worked for some time. Concern that excess heat would make the procedure unsafe for humans has broadened the search for another energy source, such as electrohydraulic drive or an external power battery. A back pack approach may provide an interim solution until materials are developed which can withstand heart activity and be small enough for implantation.

  10. Curcumin enhances human macrophage control of Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Bai, Xiyuan; Oberley-Deegan, Rebecca E; Bai, An; Ovrutsky, Alida R; Kinney, William H; Weaver, Michael; Zhang, Gong; Honda, Jennifer R; Chan, Edward D

    2016-07-01

    With the worldwide emergence of highly drug-resistant tuberculosis (TB), novel agents that have direct antimycobacterial effects or that enhance host immunity are urgently needed. Curcumin is a polyphenol responsible for the bright yellow-orange colour of turmeric, a spice derived from the root of the perennial herb Curcuma longa. Curcumin is a potent inducer of apoptosis-an effector mechanism used by macrophages to kill intracellular Mycobacterium tuberculosis (MTB). An in vitro human macrophage infection model was used to determine the effects of curcumin on MTB survival. We found that curcumin enhanced the clearance of MTB in differentiated THP-1 human monocytes and in primary human alveolar macrophages. We also found that curcumin was an inducer of caspase-3-dependent apoptosis and autophagy. Curcumin mediated these anti-MTB cellular functions, in part, via inhibition of nuclear factor-kappa B (NFκB) activation. Curcumin protects against MTB infection in human macrophages. The host-protective role of curcumin against MTB in macrophages needs confirmation in an animal model; if validated, the immunomodulatory anti-TB effects of curcumin would be less prone to drug resistance development. © 2016 Asian Pacific Society of Respirology.

  11. Thallium-201 myocardial scintigraphy and cardiac pool scintigraphy with technetium-99m labelled human serum albumin of complicated anomalous heart

    International Nuclear Information System (INIS)

    Tanaka, Minoru; Watanabe, Takashi; Murase, Mitsuya; Shimizu, Ken; Abe, Toshio

    1979-01-01

    Nuclear cardiology has been used in the diagnosis of congenital heart disease, but these studies have not shown the dramatic increase that has occurred in their use in coronary heart disease. In this report, thallium-201 myocardial scintigraphy and cardiac pool scintigraphy with technetium-99m labelled human serum albumin of 13 patients with complicated congenital heart disease were compared with contrast angiography. The application of these scanning methods to visualization of the size and shape of ventricle and interventricular septum was very useful. At times these methods give us the more accurate information about cardiac shape, especially of complicated anomalous heart, than contrast angiography. Of course these methods will never replace cardiac catheterization and contrast angiography. But these studies are non-invasive. So it was concluded that these scanning methods had better be applied in patients with complicated cardiac anomaly before invasive contrast angiography. (author)

  12. Color enhancement in multispectral image of human skin

    Science.gov (United States)

    Mitsui, Masanori; Murakami, Yuri; Obi, Takashi; Yamaguchi, Masahiro; Ohyama, Nagaaki

    2003-07-01

    Multispectral imaging is receiving attention in medical color imaging, as high-fidelity color information can be acquired by the multispectral image capturing. On the other hand, as color enhancement in medical color image is effective for distinguishing lesion from normal part, we apply a new technique for color enhancement using multispectral image to enhance the features contained in a certain spectral band, without changing the average color distribution of original image. In this method, to keep the average color distribution, KL transform is applied to spectral data, and only high-order KL coefficients are amplified in the enhancement. Multispectral images of human skin of bruised arm are captured by 16-band multispectral camera, and the proposed color enhancement is applied. The resultant images are compared with the color images reproduced assuming CIE D65 illuminant (obtained by natural color reproduction technique). As a result, the proposed technique successfully visualizes unclear bruised lesions, which are almost invisible in natural color images. The proposed technique will provide support tool for the diagnosis in dermatology, visual examination in internal medicine, nursing care for preventing bedsore, and so on.

  13. Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival.

    Science.gov (United States)

    Butts, Ryan J; Savage, Andrew J; Nietert, Paul J; Kavarana, Minoo; Moussa, Omar; Burnette, Ali L; Atz, Andrew M

    2014-12-01

    A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log-rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p HLA matching at the C locus or the DQ locus

  14. Regulatory approach to enhanced human performance during accidents

    International Nuclear Information System (INIS)

    Palla, R.L. Jr.

    1990-01-01

    It has become increasingly clear in recent years that the risk associated with nuclear power is driven by human performance. Although human errors have contributed heavily to the two core-melt events that have occurred at power reactors, effective performance during an event can also prevent a degraded situation from progressing to a more serious accident, as in the loss-of-feedwater event at Davis-Besse. Sensitivity studies in which human error rates for various categories of errors in a probabilistic risk assessment (PRA) were varied confirm the importance of human performance. Moreover, these studies suggest that actions taken during an accident are at least as important as errors that occur prior to an initiating event. A program that will lead to enhanced accident management capabilities in the nuclear industry is being developed by the US Nuclear Regulatory Commission (NRC) and industry and is a key element in NRC's integration plan for closure of severe-accident issues. The focus of the accident management (AM) program is on human performance during accidents, with emphasis on in-plant response. The AM program extends the defense-in-depth principle to plant operating staff. The goal is to take advantage of existing plant equipment and operator skills and creativity to find ways to terminate accidents that are beyond the design basis. The purpose of this paper is to describe the NRC's objectives and approach in AM as well as to discuss several human performance issues that are central to AM

  15. Relationship between the level of essential metal elements in human hair and coronary heart disease

    International Nuclear Information System (INIS)

    Bor-Tsung Hsieh; Kai-Yuan Cheng; Ying-Chen Chang

    2011-01-01

    Studies on epidemics have demonstrated the relationship between coronary heart disease (CHD) and mineral substances, such as selenium, calcium, magnesium, sodium, potassium, copper, zinc, iron, manganese, and vanadium, in human bodies. In this study, instrumental neutron activation analysis (INAA) and flame atomic absorption spectrophotometry (FAAS) were applied to evaluate the levels of selenium, calcium, magnesium, sodium, potassium, copper, zinc, and iron in healthy individuals and CHD patients. Hair samples were collected from 42 healthy participants and 28 diagnosed CHD patients. Calcium, magnesium, copper, and zinc levels in healthy individuals are significantly higher than the levels found in the patients (p < 0.01). Calcium/selenium ratio is also significantly higher in healthy individuals (p < 0.05). Based on the possible synergies and/or antagonisms of elements and their absorption and metabolism, magnesium/calcium, zinc/copper, and sodium/potassium ratios showed positive relevance (p < 0.01). (author)

  16. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.

    Directory of Open Access Journals (Sweden)

    Francesca Oltolina

    Full Text Available 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.

  17. Enhanced natural radiation exposure enhanced by human activity: the largest contributor to the Chinese population dose

    International Nuclear Information System (INIS)

    Pan Ziqiang; Liu Yanyang

    2011-01-01

    For the radiation exposure caused by human activities, the enhanced natural radiation exposure is the largest contributor to Chinese population dose. This problem has attracted social attention in recent years. Efforts have been made in several fields, such as radon indoors and in workplace, environmental problems associated with NORMs, occupational radiation hazards of non-uranium mine, and radiation dose evaluation for energy chain, but there are still many problems to be solved. In order to protect the health of workers and the public, while ensuring industrial production and economic development, it is also necessary to continue to strengthen research in all aspects above mentioned, and gradually promote the control of natural radiation exposure enhanced by human activities. (authors)

  18. Impact of intravascular enhancement, heart rate, and calcium score on diagnostic accuracy in multislice Computed Tomography coronary angiography

    International Nuclear Information System (INIS)

    Cademartiri, Filippo; Mollet, Nico R.; Kriestin, Gabriel P.; Runza, Giuseppe; Bartolotta, Tommaso Vincenzo; Galia, Massimo; Midiri, Massimo; Belgrano, Manuel; Pozzi Mucelli, Roberto

    2005-01-01

    Purpose. To assess the effect of intravascular enhancement, heart rate, and calcium score on diagnostic accuracy in the detection of significant coronary artery stenosis using 16-row multislice computed tomography (MSCT). Materials and methods. One hundred patients (88 males; 59±11 years) with suspected coronary artery disease who had undergone conventional coronary angiography (CA) and MSCT-CA were retrospectively enrolled for the study. Patients underwent a MSCT-CA, with the following protocol: collimation 16x0.75 mm, gantry rotation time 420 ms, feed/rotation 2.8 mm, kV 120, mAs 400-500. The protocol for contrast material administration was 100 ml of Iodixanol 320 mgI/nl at 4 ml/s and the scan delay was defined with a bolus tracking technique. In all patients vascular enhancement was measured in the aortic root, and the left and the right coronary arteries. The average enhancement was used to divide the population in two groups of 50 patients each, one with lower enhancement (Low), and one with higher enhancement (High). In the two groups diagnostic accuracy (per coronary segment) for the detection of significant stenosis (≥50% lumen reduction) was evaluated in vessels ≥2mm in diameter using quantitative CA as the reference standard. The differences in diagnostic accuracy were compared with a Chi-square test and a p [it

  19. Low-intensity pulsed ultrasound enhances angiogenesis and ameliorates contractile dysfunction of pressure-overloaded heart in mice.

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Ogata

    Full Text Available Chronic left ventricular (LV pressure overload causes relative ischemia with resultant LV dysfunction. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we thus examined whether LIPUS also ameliorates contractile dysfunction in LV pressure-overloaded hearts.Chronic LV pressure overload was induced with transverse aortic constriction (TAC in mice. LIPUS was applied to the whole heart three times in the first week after TAC and was repeated once a week for 7 weeks thereafter (n = 22. Animals in the control groups received the sham treatment without LIPUS (n = 23. At 8 weeks after TAC, LV fractional shortening was depressed in the TAC-Control group, which was significantly ameliorated in the TAC-LIPUS group (30.4±0.5 vs. 36.2±3.8%, P<0.05. Capillary density was higher and perivascular fibrosis was less in the LV in the TAC-LIPUS group than in the TAC-Control group. Myocardial relative ischemia evaluated with hypoxyprobe was noted in the TAC-Control group, which was significantly attenuated in the TAC-LIPUS group. In the TAC-LIPUS group, as compared with the control group, mRNA expressions of BNP and collagen III were significantly lower (both P<0.05 and protein expressions of VEGF and eNOS were significantly up-regulated associated with Akt activation (all P<0.05. No adverse effect related to the LIPUS therapy was noted.These results indicate that the LIPUS therapy ameliorates contractile dysfunction in chronically pressure-overloaded hearts through enhanced myocardial angiogenesis and attenuated perivascular fibrosis. Thus, the LIPUS therapy may be a promising, non-invasive treatment for cardiac dysfunction due to chronic pressure overload.

  20. Whole-heart 3D late gadolinium-enhanced MR imaging. Investigation of optimal scan parameters and clinical usefulness

    International Nuclear Information System (INIS)

    Yorimitsu, Misako; Yokoyama, Kenichi; Nitatori, Toshiaki; Yoshino, Hideaki; Isono, Sachiko; Kuhara, Shigehide

    2012-01-01

    Whole-heart 3-dimensional (3D) late-gadolinium-enhanced magnetic resonance (MR) imaging (WH-LGE) uses respiratory gating combined with acquisition of 3D data for the entire heart in a single scan, which permits reconstruction of any plane with high resolution. We investigated the optimal scan parameters and compared WH-LGE with the conventional scanning method. We employed inversion recovery 3D fast field echo using a 1.5-tesla system and scan parameters: repetition time (TR), 6.6 ms; echo time (TE), 2.5 ms; number of segments, 2; parallel imaging factor, 1.8; matrix size, 128 x 256; field of view (FOV), 320 x 320 mm; and acquisition slice thickness, 3 mm (reconstruction slice thickness, 1.5 mm). Five healthy volunteers underwent scanning during free breathing with real-time motion correction, from which we determined optimal scan parameters. We then used those parameters to scan 25 patients with myocardial infarction to compare scan time and image quality between the WH-LGE and conventional 3D breath-holding methods (slice thickness, 10 mm; matrix size, 128 x 256). Results in volunteers showed optimal scan parameters of 12deg flip angle, fat suppression turned off in combination, and interleaved ordering. In clinical cases, scan times did not differ significantly. Sharpness of the margins of normal myocardium at the apex of the heart and contrast between enhanced and nonenhanced myocardium improved significantly with WH-LGE. WH-LGE yields high resolution images during free breathing and is considered useful for accurately estimating the area and transmural extent of myocardial infarction. (author)

  1. An Enhanced Method to Estimate Heart Rate from Seismocardiography via Ensemble Averaging of Body Movements at Six Degrees of Freedom

    Directory of Open Access Journals (Sweden)

    Hyunwoo Lee

    2018-01-01

    Full Text Available Continuous cardiac monitoring has been developed to evaluate cardiac activity outside of clinical environments due to the advancement of novel instruments. Seismocardiography (SCG is one of the vital components that could develop such a monitoring system. Although SCG has been presented with a lower accuracy, this novel cardiac indicator has been steadily proposed over traditional methods such as electrocardiography (ECG. Thus, it is necessary to develop an enhanced method by combining the significant cardiac indicators. In this study, the six-axis signals of accelerometer and gyroscope were measured and integrated by the L2 normalization and multi-dimensional kineticardiography (MKCG approaches, respectively. The waveforms of accelerometer and gyroscope were standardized and combined via ensemble averaging, and the heart rate was calculated from the dominant frequency. Thirty participants (15 females were asked to stand or sit in relaxed and aroused conditions. Their SCG was measured during the task. As a result, proposed method showed higher accuracy than traditional SCG methods in all measurement conditions. The three main contributions are as follows: (1 the ensemble averaging enhanced heart rate estimation with the benefits of the six-axis signals; (2 the proposed method was compared with the previous SCG method that employs fewer-axis; and (3 the method was tested in various measurement conditions for a more practical application.

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

    Directory of Open Access Journals (Sweden)

    Robert S Stephenson

    Full Text Available 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(2KI, 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.

  3. BST2/Tetherin enhances entry of human cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Kasinath Viswanathan

    2011-11-01

    Full Text Available Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV, indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV.

  4. Nicotianamine, a novel enhancer of rice iron bioavailability to humans.

    Directory of Open Access Journals (Sweden)

    Luqing Zheng

    Full Text Available BACKGROUND: Polished rice is a staple food for over 50% of the world's population, but contains little bioavailable iron (Fe to meet human needs. Thus, biofortifying the rice grain with novel promoters or enhancers of Fe utilization would be one of the most effective strategies to prevent the high prevalence of Fe deficiency and iron deficiency anemia in the developing world. METHODOLOGY/PRINCIPAL FINDINGS: We transformed an elite rice line cultivated in Southern China with the rice nicotianamine synthase gene (OsNAS1 fused to a rice glutelin promoter. Endosperm overexpression of OsNAS1 resulted in a significant increase in nicotianamine (NA concentrations in both unpolished and polished grain. Bioavailability of Fe from the high NA grain, as measured by ferritin synthesis in an in vitro Caco-2 cell model that simulates the human digestive system, was twice as much as that of the control line. When added at 1:1 molar ratio to ferrous Fe in the cell system, NA was twice as effective when compared to ascorbic acid (one of the most potent known enhancers of Fe bioavailability in promoting more ferritin synthesis. CONCLUSIONS: Our data demonstrated that NA is a novel and effective promoter of iron utilization. Biofortifying polished rice with this compound has great potential in combating global human iron deficiency in people dependent on rice for their sustenance.

  5. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells.

    Science.gov (United States)

    Chen, Li; Hu, Huimin; Qiu, Weimin; Shi, Kaikai; Kassem, Moustapha

    2018-05-01

    Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Microneedle Enhanced Delivery of Cosmeceutically Relevant Peptides in Human Skin

    Science.gov (United States)

    Mohammed, Yousuf H.; Yamada, Miko; Lin, Lynlee L.; Grice, Jeffrey E.; Roberts, Michael S.; Raphael, Anthony P.; Benson, Heather A. E.; Prow, Tarl W.

    2014-01-01

    Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides. PMID:25033398

  7. Microneedle enhanced delivery of cosmeceutically relevant peptides in human skin.

    Directory of Open Access Journals (Sweden)

    Yousuf H Mohammed

    Full Text Available Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides.

  8. Endurance training enhances BDNF release from the human brain

    DEFF Research Database (Denmark)

    Seifert, Thomas; Brassard, Patrice; Wissenberg, Mads

    2010-01-01

    The circulating level of brain-derived neurotrophic factor (BDNF) is reduced in patients with major depression and type-2 diabetes. Because acute exercise increases BDNF production in the hippocampus and cerebral cortex, we hypothesized that endurance training would enhance the release of BDNF from...... the human brain as detected from arterial and internal jugular venous blood samples. In a randomized controlled study, 12 healthy sedentary males carried out 3 mo of endurance training (n = 7) or served as controls (n = 5). Before and after the intervention, blood samples were obtained at rest and during...... exercise. At baseline, the training group (58 + or - 106 ng x 100 g(-1) x min(-1), means + or - SD) and the control group (12 + or - 17 ng x 100 g(-1) x min(-1)) had a similar release of BDNF from the brain at rest. Three months of endurance training enhanced the resting release of BDNF to 206 + or - 108...

  9. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Hu, Huimin; Qiu, Weimin

    2018-01-01

    Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined...... differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte...... differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating h...

  10. Estramustine: A novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Ryu, S.; Gabel, M.; Khil, M.S.

    1994-01-01

    Estramustine (EM), an antimicrotubule agent, binds microtubule-associated proteins, causes spindle disassembly, and arrests cells at the late G 2 /M phase of the cell cycle. Since cells in the G 2 /M phase are the most radiosensitive and some human cancer cells contain high level of EM-binding protein, experiments were carried out to determine whether radiation sensitization could be obtained in human carcinoma cells. Cells containing a high level of EM-binding protein such as prostate carcinoma (DU-145), breast carcinoma (MCF-7), and malignant glioma (U-251) were used to demonstrate radiosensitization. Cervical carcinoma (HeLa-S 3 ) and colon carcinoma (HT-29) cells which are not known to contain EM-binding protein were also employed. Cell survival was assayed by the colony forming ability of single plated cells in culture to obtain dose-survival curves. Pretreatment of DU-145, MCF-7, and U-251 cells to a nontoxic concentration (5 μM) of EM for more than one cell cycle time, substantially enhanced the radiation-induced cytotoxicity. The sensitizer enhancement ratio of these cells ranged from 1.35-1.52. The magnitude of the enhancement was dependent on the drug concentration and exposure time. The rate of cell accumulation in G 2 /M phase, as determined by flow cytometry, increased with longer treatment time in the cell lines which showed radiosensitization. Other antimicrotubule agents such as taxol and vinblastine caused minimal or no radiosensitization at nontoxic concentrations. The data provide a radiobiological basis for using EM as a novel radiation enhancer, with the property of tissue selectivity. 29 refs., 4 figs., 1 tab

  11. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

    Directory of Open Access Journals (Sweden)

    Li Chen

    2018-05-01

    Full Text Available Human stromal stem cells (hMSCs differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs: Cofilin 1 (CFL1 and Destrin (DSTN or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4. In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1 which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation. Keywords: Actin cytoskeleton, Actin depolymerizing factors, Adipocyte differentiation, Human stromal stem cells

  12. Adopting a music-to-heart rate alignment strategy to measure the impact of music and its tempo on human heart rate

    OpenAIRE

    Van Dyck, Edith; Six, Joren; Soyer, Esin Nisa; Denys, Marlies; Bardijn, Ilka; Leman, Marc

    2017-01-01

    Music is frequently used as a means of relaxation. Conversely, it is used as a means of arousal in sports and exercise contexts. Previous research suggests that tempo is one of the most significant determinants of music-related arousal and relaxation effects. Here we investigate the specific effect of music tempo, but also more generally, the influence of music on human heart rate. We took the pulses of 32 participants in silence, and then we played them non-vocal, ambient music at a tempo co...

  13. Tailoring consumer resources to enhance self-care in chronic heart failure.

    Science.gov (United States)

    Driscoll, Andrea; Davidson, Patricia; Clark, Robyn; Huang, Nancy; Aho, Zoe

    2009-08-01

    Chronic heart failure (CHF) is associated with high hospitalisation and mortality rates and debilitating symptoms. In an effort to reduce hospitalisations and improve symptoms individuals must be supported in managing their condition. Patients who can effectively self-manage their symptoms through lifestyle modification and adherence to complex medication regimens will experience less hospitalisations and other adverse events. The purpose of this paper is to explain how providing evidence-based information, using patient education resources, can support self-care. Self-care relates to the activities that individuals engage in relation to health seeking behaviours. Supporting self-care practices through tailored and relevant information can provide patients with resources and advice on strategies to manage their condition. Evidence-based approaches to improve adherence to self-care practices in patients with heart failure are not often reported. Low health literacy can result in poor understanding of the information about CHF and is related to adverse health outcomes. Also a lack of knowledge can lead to non-adherence with self-care practices such as following fluid restriction, low sodium diet and daily weighing routines. However these issues need to be addressed to improve self-management skills. Recently the Heart Foundation CHF consumer resource was updated based on evidence-based national clinical guidelines. The aim of this resource is to help consumers improve understanding of the disease, reduce uncertainty and anxiety about what to do when symptoms appear, encourage discussions with local doctors, and build confidence in self-care management. Evidence-based CHF patient education resources promote self-care practices and early detection of symptom change that may reduce hospitalisations and improve the quality of life for people with CHF.

  14. Profile of Heart Donors from the Human Valve Bank of the Santa Casa de Misericórdia de Curitiba.

    Science.gov (United States)

    Ferreira, Renata Maria; da Costa, Marise Teresinha Brenner Affonso; Canciglieri Junior, Osiris; Sant'Anna, Ângelo Márcio Oliveira

    2016-04-01

    Human heart valves are used as replacement valves and have satisfactory functional results compared with conventional prostheses. Characterize the profile of effective heart donors from the human valve bank of the santa casa de misericórdia de curitiba and analyze the association between the profile variables. It consists of a retrospective and quantitative study of electronic medical records from heart donors for heart valves. every heart donation made to the bank between january 2004 and december 2014 was studied. 2,149 donations were analyzed, from donors aged 0 to 71 years old, with an average of 34.9 ± 15.03 years old. most donors were male 65.7% (n=1,411) and 34.3% (n=738) were female. among the most frequent causes of the donors' death are trauma at 53% (n=1,139) and cerebral vascular accident at 34.2% (n=735). there was significant statistical association between the analyzed variables. There has been an improvement in brazil's donation rate, being essential that the tissue banks work together with the state and federal district centers for notification, procurement and distribution of organs in order to increase the number of donors.

  15. Image enhancement using thermal-visible fusion for human detection

    Science.gov (United States)

    Zaihidee, Ezrinda Mohd; Hawari Ghazali, Kamarul; Zuki Saleh, Mohd

    2017-09-01

    An increased interest in detecting human beings in video surveillance system has emerged in recent years. Multisensory image fusion deserves more research attention due to the capability to improve the visual interpretability of an image. This study proposed fusion techniques for human detection based on multiscale transform using grayscale visual light and infrared images. The samples for this study were taken from online dataset. Both images captured by the two sensors were decomposed into high and low frequency coefficients using Stationary Wavelet Transform (SWT). Hence, the appropriate fusion rule was used to merge the coefficients and finally, the final fused image was obtained by using inverse SWT. From the qualitative and quantitative results, the proposed method is more superior than the two other methods in terms of enhancement of the target region and preservation of details information of the image.

  16. Fibroblast Growth Factor-9 Activates c-Kit Progenitor Cells and Enhances Angiogenesis in the Infarcted Diabetic Heart

    Directory of Open Access Journals (Sweden)

    Dinender Singla

    2016-01-01

    Full Text Available We hypothesized that fibroblast growth factor-9 (FGF-9 would enhance angiogenesis via activating c-kit positive stem cells in the infarcted nondiabetic and diabetic heart. In brief, animals were divided into three groups: Sham, MI, and MI+FGF-9. Two weeks following MI or sham surgery, our data suggest that treatment with FGF-9 significantly diminished vascular apoptosis compared to the MI group in both C57BL/6 and db/db mice (p<0.05. Additionally, the number of c-kit+ve/SM α-actin+ve cells and c-kit+ve/CD31+ve cells were greatly enhanced in the MI+FGF-9 groups relative to the MI suggesting FGF-9 enhances c-Kit cell activation and their differentiation into vascular smooth muscle cells and endothelial cells, respectively (p<0.05. Histology shows that the total number of vessels were quantified for all groups and our data suggest that the FGF-9 treated groups had significantly more vessels than their MI counterparts (p<0.05. Finally, echocardiographic data suggests a significant improvement in left ventricular output, as indicated by fractional shortening and ejection fraction in both nondiabetic and diabetic animals treated with FGF-9 (p<0.05. Overall, our data suggests FGF-9 has the potential to attenuate vascular cell apoptosis, activate c-Kit progenitor cells, and enhance angiogenesis and neovascularization in C57BL/6 and db/db mice leading to improved cardiac function.

  17. CONSUMPTION OF SATURATED ANIMAL FATS IN THE DIET OF HUMANS MAY DECREASE THE RATE OF HEART DISEASE IN THE FUTURE

    OpenAIRE

    Somayeh Zaminpira; Sorush Niknamian

    2017-01-01

    Fats, as part of the human dietary regime are a concentrated source of energy. Animals contain saturated and plants contain unsaturated type of fatty acids. In this prospective research, the role of animal saturated fatty acids is highlighted and is proven to be a rational dietary source for the human diet. Saturated fats consumption is a wise choice in order to reduce the coronary heart disease risk, although it is believed in an opposite way. Researching through the healthiest tribes and kn...

  18. The effect of excess expression of GFP in a novel heart-specific green fluorescence zebrafish regulated by nppa enhancer at early embryonic development.

    Science.gov (United States)

    Huang, Wen; Deng, Yun; Dong, Wei; Yuan, Wuzhou; Wan, Yongqi; Mo, Xiaoyan; Li, Yongqing; Wang, Zequn; Wang, Yuequn; Ocorr, Karen; Zhang, Bo; Lin, Shuo; Wu, Xiushan

    2011-02-01

    In order to study the impalpable effect of GFP in homozygous heart-specific GFP-positive zebrafish during the early stage, the researchers analyzed the heart function of morphology and physiology at the first 3 days after fertilization. This zebrafish line was produced by a large-scale Tol2 transposon mediated enhancer trap screen that generated a transgenic zebrafish with a heart-specific expression of green fluorescent protein (GFP)-tagged under control of the nppa enhancer. In situ hybridization experiments showed that the nppa:GFP line faithfully recapitulated both the spatial and temporal expressions of the endogenous nppa. Green fluorescence was intensively and specifically expressed in the myocardial cells located both in the heart chambers and in the atrioventricular canal. The embryonic heart of nppa:GFP line developed normally compared with those in the wild type. There was no difference between the nappa:GFP and wild type lines with respect to heart rate, overall size, ejection volume, and fractional shortening. Thus the excess expression of GFP in this transgenic line seemed to exert no detrimental effects on zebrafish hearts during the early stages.

  19. Human engineered heart tissue as a model system for drug testing.

    Science.gov (United States)

    Eder, Alexandra; Vollert, Ingra; Hansen, Arne; Eschenhagen, Thomas

    2016-01-15

    Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

    Energy Technology Data Exchange (ETDEWEB)

    Mongillo, Marco; Leccisotti, Lucia [Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, London (United Kingdom); John, Anna S. [Hammersmith Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom); Pennell, Dudley J. [Royal Brompton Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom); Camici, Paolo G. [Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, London (United Kingdom); Hammersmith Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom)

    2007-08-15

    We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic {beta}-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Eight patients (aged 67 {+-} 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 {+-} 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [{sup 11}C]meta-hydroxy-ephedrine (HED) volume of distribution (V{sub d}) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 {+-} 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 {+-} 6 years, p < 0.01 vs patients) data. MGU in patients was reduced in both normal remote (0.44 {+-} 0.14 {mu}mol.min{sup -1}.g{sup -1}) and dysfunctional (0.49 {+-} 0.14 {mu}mol.min{sup -1}.g{sup -1}) segments compared with controls (0.61 {+-} 0.7 {mu}mol.min{sup -1}.g{sup -1}; p < 0.001 vs both). HED V{sub d} was reduced in dysfunctional segments of patients (38.9 {+-} 21.2 ml.g{sup -1}) compared with normal segments (52.2 {+-} 19.6 ml.g{sup -1}) and compared with controls (62.7 {+-} 11.3 ml.g{sup -1}). In patients, regional MGU was correlated with HED V{sub d}. The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. (orig.)

  1. 31P MR spectroscopic measurement of intracellular pH in normal human hearts

    International Nuclear Information System (INIS)

    Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min

    2002-01-01

    To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of γ-ATP after performing MRS with ECG-gated two-dimensional 31 P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled 31 P CSI was performed on a 1.5-T scanner using a 1 H 31 P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of α-, β-, γ-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and γ-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm (γ-ATP), -7.8 ppm (α-ATP), and -16.3 ppm (β-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/β-ATP ratio was 2.20±0.17 and the PDE/β-ATP ratio, 1.04±0.09 pHi readings were 7.31±0.23 (calculated by the shift of Pi) and 6.81±0.20 (calculated by the shift of γ-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method

  2. {sup 31}P MR spectroscopic measurement of intracellular pH in normal human hearts

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min [Kyungpook National Univ., Taegu (Korea, Republic of)] [and others

    2002-05-01

    To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of {gamma}-ATP after performing MRS with ECG-gated two-dimensional {sup 31}P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled {sup 31}P CSI was performed on a 1.5-T scanner using a {sup 1}H{sup 31}P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of {alpha}-, {beta}-, {gamma}-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and {gamma}-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm ({gamma}-ATP), -7.8 ppm ({alpha}-ATP), and -16.3 ppm ({beta}-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/{beta}-ATP ratio was 2.20{+-}0.17 and the PDE/{beta}-ATP ratio, 1.04{+-}0.09 pHi readings were 7.31{+-}0.23 (calculated by the shift of Pi) and 6.81{+-}0.20 (calculated by the shift of {gamma}-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method.

  3. Elasticity-based determination of isovolumetric phases in the human heart

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    Braun Jürgen

    2010-10-01

    Full Text Available Abstract Background/Motivation To directly determine isovolumetric cardiac time intervals by magnetic resonance elastography (MRE using the magnitude of the complex signal for deducing morphological information combined with the phase of the complex signal for tension-relaxation measurements. Methods Thirty-five healthy volunteers and 11 patients with relaxation abnormalities were subjected to transthoracic wave stimulation using vibrations of approximately 25 Hz. A k-space-segmented, ECG-gated gradient-recalled echo steady-state sequence with a 500-Hz bipolar motion-encoding gradient was used for acquiring a series of 360 complex images of a short-axis view of the heart at a frame rate of less than 5.2 ms. Magnitude images were employed for measuring the cross-sectional area of the left ventricle, while phase images were used for analyzing the amplitudes of the externally induced waves. The delay between the decrease in amplitude and onset of ventricular contraction was determined in all subjects and assigned to the time of isovolumetric tension. Conversely, the delay between the increase in wave amplitude and ventricular dilatation was used for measuring the time of isovolumetric elasticity relaxation. Results Wave amplitudes decreased during systole and increased during diastole. The variation in wave amplitude occurred ahead of morphological changes. In healthy volunteers the time of isovolumetric elasticity relaxation was 75 ± 31 ms, which is significantly shorter than the time of isovolumetric tension of 136 ± 36 ms (P n = 11 isovolumetric elasticity relaxation was significantly prolonged, with 133 ± 57 ms (P P = 0.053. Conclusion The complex MRE signal conveys complementary information on cardiac morphology and elasticity, which can be combined for directly measuring isovolumetric tension and elasticity relaxation in the human heart.

  4. Using the Human Activity Profile to Assess Functional Performance in Heart Failure.

    Science.gov (United States)

    Ribeiro-Samora, Giane Amorim; Pereira, Danielle Aparecida Gomes; Vieira, Otávia Alves; de Alencar, Maria Clara Noman; Rodrigues, Roseane Santo; Carvalho, Maria Luiza Vieira; Montemezzo, Dayane; Britto, Raquel Rodrigues

    2016-01-01

    To investigate (1) the validity of using the Human Activity Profile (HAP) in patients with heart failure (HF) to estimate functional capacity; (2) the association between the HAP and 6-Minute Walk Test (6MWT) distance; and (3) the ability of the HAP to differentiate between New York Heart Association (NYHA) functional classes. In a cross-sectional study, we evaluated 62 clinically stable patients with HF (mean age, 47.98 years; NYHA class I-III). Variables included maximal functional capacity as measured by peak oxygen uptake ((Equation is included in full-text article.)O2) using a cardiopulmonary exercise test (CPET), peak (Equation is included in full-text article.)O2 as estimated by the HAP, and exercise capacity as measured by the 6MWT. The difference between the measured (CPET) and estimated (HAP) peak (Equation is included in full-text article.)O2 against the average values showed a bias of 2.18 mL/kg/min (P = .007). No agreement was seen between these measures when applying the Bland-Altman method. Peak (Equation is included in full-text article.)O2 in the HAP showed a moderate association with the 6MWT distance (r = 0.62; P < .0001). Peak (Equation is included in full-text article.)O2 in the HAP was able to statistically differentiate NYHA functional classes I, II, and III (P < .05). The estimated peak (Equation is included in full-text article.)O2 using the HAP was not concordant with the gold standard CPET measure. On the contrary, the HAP was able to differentiate NYHA functional class associated with the 6MWT distance; therefore, the HAP is a useful tool for assessing functional performance in patients with HF.

  5. Morphologic expression of the left coronary artery in pigs. An approach in relation to human heart

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    Fabian Alejandro Gómez

    2014-04-01

    Full Text Available Introduction: In spite of its importance as an experimental model, the information on the left coronary artery in pigs is sparse. Objective: To determine the morphologic features of the left coronary artery in pigs. Methods: We evaluated 158 pig hearts. The left coronary artery was perfused with synthetic resin after their ostia had been catheterized. Diameters and courses of the vascular beds were measured with an electronic caliper (Mitutoyo(r. Results: The diameter of left coronary artery was 6.98 ± 1.56 mm and its length was 3.51±0.99 mm. It was found to end up by bifurcating itself into the anterior interventricular artery and the circumflex artery in 79% of the cases, and by trifurcating in 21% of the cases, with the presence of the diagonal artery. The anterior interventricular artery ended up at the apex in 79.7% of the cases, and the circumflex artery at the posterior aspect of the left ventricle in 64% of the case, this artery never reached the posterior interventricular sulcus. An anastomosis between the terminal branches of the anterior interventricular artery and the posterior interventricular artery was found in 7.6% of the specimens. The antero-superior branch of the anterior interventricular artery occurred in 89.9% of the hearts. A left marginal branch was observed in 87.9% of the cases with a diameter of 2.25±0.55 mm. Conclusion: Compared with humans, pigs have shorter left coronary artery trunks and branches; even the circumflex artery never reaches the posterior interventricular sulcus. Our findings are useful for the design of experimental hemodynamic and procedural models.

  6. Hunger enhances consistent economic choices in non-human primates.

    Science.gov (United States)

    Yamada, Hiroshi

    2017-05-24

    Hunger and thirst are fundamental biological processes that drive consumption behavior in humans and non-human animals. While the existing literature in neuroscience suggests that these satiety states change how consumable rewards are represented in the brain, it remains unclear as to how they change animal choice behavior and the underlying economic preferences. Here, I used combined techniques from experimental economics, psychology, and neuroscience to measure food preferences of marmoset monkeys (Callithrix jacchus), a recently developed primate model for neuroscience. Hunger states of animals were manipulated by scheduling feeding intervals, resulting in three different conditions: sated, non-sated, and hungry. During these hunger states, animals performed pairwise choices of food items, which included all possible pairwise combinations of five different food items except for same-food pairs. Results showed that hunger enhanced economic rationality, evident as a decrease of transitivity violations (item A was preferred to item B, and B to C, but C was preferred to A). Further analysis demonstrated that hungry monkeys chose more-preferred items over less-preferred items in a more deterministic manner, while the individual food preferences appeared to remain stable across hunger states. These results suggest that hunger enhances consistent choice behavior and shifts animals towards efficient outcome maximization.

  7. Procreative liberty, enhancement and commodification in the human cloning debate.

    Science.gov (United States)

    Shapshay, Sandra

    2012-12-01

    The aim of this paper is to scrutinize a contemporary standoff in the American debate over the moral permissibility of human reproductive cloning in its prospective use as a eugenic enhancement technology. I shall argue that there is some significant and under-appreciated common ground between the defenders and opponents of human cloning. Champions of the moral and legal permissibility of cloning support the technology based on the right to procreative liberty provided it were to become as safe as in vitro fertilization and that it be used only by adults who seek to rear their clone children. However, even champions of procreative liberty oppose the commodification of cloned embryos, and, by extension, the resulting commodification of the cloned children who would be produced via such embryos. I suggest that a Kantian moral argument against the use of cloning as an enhancement technology can be shown to be already implicitly accepted to some extent by champions of procreative liberty on the matter of commodification of cloned embryos. It is in this argument against commodification that the most vocal critics of cloning such as Leon Kass and defenders of cloning such as John Robertson can find greater common ground. Thus, I endeavor to advance the debate by revealing a greater degree of moral agreement on some fundamental premises than hitherto recognized.

  8. A simulation study of the reaction of human heart to biphasic electrical shocks

    Directory of Open Access Journals (Sweden)

    Seemann Gunnar

    2004-06-01

    Full Text Available Abstract Background This article presents a study, which examines the effects of biphasic electrical shocks on human ventricular tissue. The effects of this type of shock are not yet fully understood. Animal experiments showed the superiority of biphasic shocks over monophasic ones in defibrillation. A mathematical computer simulation can increase the knowledge of human heart behavior. Methods The research presented in this article was done with different models representing a three-dimensional wedge of ventricular myocardium. The electrophysiology was described with Priebe-Beuckelmann model. The realistic fiber twist, which is specific to human myocardium was included. Planar electrodes were placed at the ends of the longest side of the virtual cardiac wedge, in a bath medium. They were sources of electrical shocks, which varied in magnitude from 0.1 to 5 V. In a second arrangement ring electrodes were placed directly on myocardium for getting a better view on secondary electrical sources. The electrical reaction of the tissue was generated with a bidomain model. Results The reaction of the tissue to the electrical shock was specific to the initial imposed characteristics. Depolarization appeared in the first 5 ms in different locations. A further study of the cardiac tissue behavior revealed, which features influence the response of the considered muscle. It was shown that the time needed by the tissue to be totally depolarized is much shorter when a biphasic shock is applied. Each simulation ended only after complete repolarization was achieved. This created the possibility of gathering information from all states corresponding to one cycle of the cardiac rhythm. Conclusions The differences between the reaction of the homogeneous tissue and a tissue, which contains cleavage planes, reveals important aspects of superiority of biphasic pulses. ...

  9. Improving human object recognition performance using video enhancement techniques

    Science.gov (United States)

    Whitman, Lucy S.; Lewis, Colin; Oakley, John P.

    2004-12-01

    Atmospheric scattering causes significant degradation in the quality of video images, particularly when imaging over long distances. The principle problem is the reduction in contrast due to scattered light. It is known that when the scattering particles are not too large compared with the imaging wavelength (i.e. Mie scattering) then high spatial resolution information may be contained within a low-contrast image. Unfortunately this information is not easily perceived by a human observer, particularly when using a standard video monitor. A secondary problem is the difficulty of achieving a sharp focus since automatic focus techniques tend to fail in such conditions. Recently several commercial colour video processing systems have become available. These systems use various techniques to improve image quality in low contrast conditions whilst retaining colour content. These systems produce improvements in subjective image quality in some situations, particularly in conditions of haze and light fog. There is also some evidence that video enhancement leads to improved ATR performance when used as a pre-processing stage. Psychological literature indicates that low contrast levels generally lead to a reduction in the performance of human observers in carrying out simple visual tasks. The aim of this paper is to present the results of an empirical study on object recognition in adverse viewing conditions. The chosen visual task was vehicle number plate recognition at long ranges (500 m and beyond). Two different commercial video enhancement systems are evaluated using the same protocol. The results show an increase in effective range with some differences between the different enhancement systems.

  10. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Science.gov (United States)

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  11. Effects of Moxa (Folium Artemisiae argyi Smoke Exposure on Heart Rate and Heart Rate Variability in Healthy Young Adults: A Randomized, Controlled Human Study

    Directory of Open Access Journals (Sweden)

    Yingxue Cui

    2013-01-01

    Full Text Available Objective. To determine the effects of the moxa smoke on human heart rate (HR and heart rate variability (HRV. Methods. Fifty-five healthy young adults were randomly divided into experimental (n=28 and control (n=27 groups. Experimental subjects were exposed to moxa smoke (2.5 ± 0.5 mg/m3 twice for 25 minutes in one week. ECG monitoring was performed before, during, and after exposure. Control subjects were exposed to normal indoor air in a similar environment and similarly monitored. Followup was performed the following week. Short-term (5 min HRV parameters were analyzed with HRV analysis software. SPSS software was used for statistical analysis. Results. During and after the first exposure, comparison of percentage changes or changes in all parameters between groups showed no significant differences. During the second exposure, percentage decrease in HR, percentage increases in lnTP, lnHF, lnLF, and RMSSD, and increase in PNN50 were significantly greater in the experimental group than in control. Conclusion. No significant adverse HRV effects were associated with this clinically routine 25-minute exposure to moxa smoke, and the data suggests that short-term exposure to moxa smoke might have positive regulating effects on human autonomic function. Further studies are warranted to confirm these findings.

  12. Combined effect of whole-body vibration and ambient lighting on human discomfort, heart rate, and reaction time.

    Science.gov (United States)

    Monazzam, Mohammad Reza; Shoja, Esmaeil; Zakerian, Seyed Abolfazl; Foroushani, Abbas Rahimi; Shoja, Mohsen; Gharaee, Masoumeh; Asgari, Amin

    2018-03-12

    This study aimed to investigate the effect of whole-body vibration and ambient lighting, as well as their combined effect on human discomfort, heart rate, and reaction time in laboratory conditions. 44 men were recruited with an average age of 25.4 ± 1.9 years. Each participant was subjected to 12 experimental steps, each step lasting five minutes for four different vibration accelerations in X, Y, and Z axes at a fixed frequency; three different lighting intensities of 50, 500, and 1000 lx were also considered. At each step, a visual computerized reaction test was taken from subjects and their heart rate recorded by pulse oximeter. In addition, the discomfort rate of subjects was measured using Borg scale. Increasing vibration acceleration significantly increased the discomfort rate and heart beat but not the reaction time. Lack of lighting caused more discomfort in the subjects, but there was no significant correlation between lighting intensity with heart rate and reaction time. The results also showed that the combined effect of vibration and lighting had no significant effect on any of the discomfort, heart rate, and reaction time variables. Whole-body vibration is an important factor in the development of human subjective and physiological reactions compared to lighting. Therefore, consideration of the level of vibration to which an individual is exposed in workplaces subject to vibration plays an important role in reducing the level of human discomfort, but its interaction with ambient lighting does not have a significant effect on human subjective and physiological responses.

  13. Contribution of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort.

    Science.gov (United States)

    Sliwa, Karen; Carrington, Melinda J; Becker, Anthony; Thienemann, Friedrich; Ntsekhe, Mpiko; Stewart, Simon

    2012-04-01

    The contemporary impact of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic on heart disease in South Africa (>5 million people affected) is unknown. The Heart of Soweto Study provides a unique opportunity to identify the contribution of cardiac manifestations of this epidemic to de novo presentations of heart disease in an urban African community in epidemiological transition. Chris Hani Baragwanath Hospital services the >1 million people living in Soweto, South Africa. A prospective, clinical registry captured data from all de novo cases of heart disease presenting to the Cardiology Unit during 2006-08. We describe all cases where HIV/AIDS was concurrently diagnosed. Overall, 518 of 5328 de novo cases of heart disease were identified as HIV-positive (9.7%) with 54% of these prescribed highly active anti-retroviral therapies on presentation. Women (62%) and Africans (97%) predominated with women being significantly younger than men 38 ± 13 vs. 42 ± 13 years (P = 0.002). The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (196 cases, 38%); being prescribed more anti-retroviral therapy (127/196 vs. 147/322; odds ratio 2.85, 95% confidence interval 1.81-3.88) with higher viral loads [median 110 000 (inter-quartile range 26 000-510 000) vs. 19 000 (3200-87 000); P = 0.018] and a lower CD4 count [median 180 (71-315) vs. 211 (96-391); P = 0.019] than the rest. An additional 128 cases (25%) were diagnosed with pericarditis/pericardial effusion with a range of other concurrent diagnoses evident, including 42 cases (8.1%) of HIV-related pulmonary arterial hypertension. Only 14 of all 581 cases of coronary artery disease (CAD) (2.4%, mean age 41 ± 13 years) were confirmed HIV-positive. Cardiac manifestations of HIV/AIDS identified within this cohort were relatively infrequent. While HIV-related cardiomyopathy and pericardial disease remain important targets for early detection and treatment in

  14. Overview Electrotactile Feedback for Enhancing Human Computer Interface

    Science.gov (United States)

    Pamungkas, Daniel S.; Caesarendra, Wahyu

    2018-04-01

    To achieve effective interaction between a human and a computing device or machine, adequate feedback from the computing device or machine is required. Recently, haptic feedback is increasingly being utilised to improve the interactivity of the Human Computer Interface (HCI). Most existing haptic feedback enhancements aim at producing forces or vibrations to enrich the user’s interactive experience. However, these force and/or vibration actuated haptic feedback systems can be bulky and uncomfortable to wear and only capable of delivering a limited amount of information to the user which can limit both their effectiveness and the applications they can be applied to. To address this deficiency, electrotactile feedback is used. This involves delivering haptic sensations to the user by electrically stimulating nerves in the skin via electrodes placed on the surface of the skin. This paper presents a review and explores the capability of electrotactile feedback for HCI applications. In addition, a description of the sensory receptors within the skin for sensing tactile stimulus and electric currents alsoseveral factors which influenced electric signal to transmit to the brain via human skinare explained.

  15. Flat panel computed tomography of human ex vivo heart and bone specimens: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaou, Konstantin; Becker, Christoph R.; Reiser, Maximilian F. [Ludwig-Maximilians-University, Department of Clinical Radiology, Munich (Germany); Flohr, Thomas; Stierstorfer, Karl [CT Division, Siemens Medical Solutions, Forchheim (Germany)

    2005-02-01

    The aim of this technical investigation was the detailed description of a prototype flat panel detector computed tomography system (FPCT) and its initial evaluation in an ex vivo setting. The prototype FPCT scanner consists of a conventional radiographic flat panel detector, mounted on a multi-slice CT scanner gantry. Explanted human ex vivo heart and foot specimens were examined. Images were reformatted with various reconstruction algorithms and were evaluated for high-resolution anatomic information. For comparison purposes, the ex vivo specimens were also scanned with a conventional 16-detector-row CT scanner (Sensation 16, Siemens Medical Solutions, Forchheim, Germany). With the FPCT prototype used, a 1,024 x 768 resolution matrix can be obtained, resulting in an isotropic voxel size of 0.25 x 0.25 x 0.25 mm at the iso-center. Due to the high spatial resolution, very small structures such as trabecular bone or third-degree, distal branches of coronary arteries could be visualized. This first evaluation showed that flat panel detector systems can be used in a cone-beam computed tomography scanner and that very high spatial resolutions can be achieved. However, there are limitations for in vivo use due to constraints in low contrast resolution and slow scan speed. (orig.)

  16. Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts.

    Science.gov (United States)

    Mori, M; Takeuchi, M; Takaoka, H; Hata, K; Hayashi, Y; Yamakawa, H; Yokoyama, M

    1997-03-01

    The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.

  17. Effect of propionyl-L-carnitine on L-type calcium channels in human heart sarcolemma

    International Nuclear Information System (INIS)

    Bevilacqua, M.; Vago, T.; Norbiato, G.

    1991-01-01

    Propionyl-L-carnitine (PC) protects perfused rat hearts against damage by ischemia-reperfusion. Activation of L-type calcium channel play a role on ischemia-reperfusion damage. Therefore, we studied the effect of PC on some properties of L-type calcium channels in an in vitro preparation from human myocardium sarcolemma (from patients with idiopathic dilated cardiomyopathy). Binding of the L-type calcium channel blockers isradipine [ 3 H]-PN 200-110 (PN) to plasma membrane preparations revealed a single population of binding sites (total number: Bmax = 213 +/- 34 fM/mg protein and affinity: Kd = 152 +/- 19 nM; n = 6). The characteristics of these binding sites were evaluated in the presence and in the absence of Ca 2+ and of calcium blockers (D-888, a verapamillike drug, and diltiazem). Incubation in a Ca 2+ -containing buffer increased the affinity of PN binding sites. Binding sites for PN were modulated by organic calcium channel blockers; in competition isotherms at 37 degree C, D-888 (desmethoxyverapamil) decreased the PN binding, whereas diltiazem increased it. These results strongly suggest that the site labelled by PN is the voltage-operated calcium channel of the human myocardium. The addition of PC (1 mM) to plasma membranes labelled with PN at 37 degree C decreased the affinity of the binding; this effect was counteracted by the addition of Ca 2+ to the medium. This result was consistent with a competition between Ca 2+ and PC. The effect of PC incubation at 4 degree C was the opposite; at this temperature PC increased the affinity of the binding sites and the effect was obscured by Ca 2+

  18. Bee venom enhances the differentiation of human regulatory T cells.

    Science.gov (United States)

    Caramalho, I; Melo, A; Pedro, E; Barbosa, M M P; Victorino, R M M; Pereira Santos, M C; Sousa, A E

    2015-10-01

    Venom-specific immunotherapy (VIT) is well recognized by its efficacy, and compelling evidence implicates regulatory T cells (Tregs) in the underlying tolerogenic mechanisms. Additionally, hymenoptera venom has for a long time been claimed to modulate immunity. Here, we investigated the putative role of bee venom (Bv) in human FOXP3-expressing Treg homeostasis and differentiation, irrespective of the donors' allergic status. We found that Bv significantly enhanced the differentiation of FOXP3-expressing cells both from conventional naïve CD4 T cells and mature CD4 thymocytes, a property that may contribute to the VIT's capacity to expand circulating Tregs in allergic individuals. We expect that our data enlightening the Treg-mediated immunomodulatory properties of Bv regardless of TCR specificity, to have application in other allergies, as well as in other clinical settings, such as autoimmunity and transplantation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Human PrimPol activity is enhanced by RPA.

    Science.gov (United States)

    Martínez-Jiménez, María I; Lahera, Antonio; Blanco, Luis

    2017-04-10

    Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.

  20. A New Approach to Heart Valve Tissue Engineering Based on Modifying Autologous Human Pericardium by 3D Cellular Mechanotransduction

    Czech Academy of Sciences Publication Activity Database

    Straka, František; Schorník, David; Mašín, J.; Filová, Elena; Miřejovský, T.; Burdíková, Z.; Švindrych, Z.; Chlup, H.; Horný, L.; Veselý, J.; Pirk, J.; Bačáková, Lucie

    2017-01-01

    Roč. 7, č. 7 (2017), s. 527-543 ISSN 2157-9083 R&D Projects: GA MZd(CZ) NV15-29153A; GA MZd(CZ) NT11270 Institutional support: RVO:67985823 Keywords : autologous human pericardium * pericardial interstitial cells * heart valve * 3D mechanotranduction * bioreactor Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Cardiac and Cardiovascular systems Impact factor: 1.383, year: 2016

  1. Effects of Adenovirus-Mediated Delivery of the Human Hepatocyte Growth Factor Gene in Experimental Radiation-Induced Heart Disease

    International Nuclear Information System (INIS)

    Hu Shunying; Chen Yundai; Li Libing; Chen Jinlong; Wu Bin; Zhou, Xiao; Zhi Guang; Li Qingfang; Wang Rongliang; Duan Haifeng; Guo Zikuan; Yang Yuefeng; Xiao Fengjun; Wang Hua; Wang Lisheng

    2009-01-01

    Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 ± 9.01 vs. 41.94 ± 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 ± 1303 vs. 1667 ± 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 ± 1084 vs. 1566 ± 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.

  2. Heart Rate Variability (HRV) biofeedback: A new training approach for operator’s performance enhancement

    OpenAIRE

    Auditya Purwandini Sutarto; Muhammad Nubli Abdul Wahab; Nora Mat Zin

    2010-01-01

    The widespread implementation of advanced and complex systems requires predominantly operators’ cognitive functions and less importance of human manual control. On the other hand, most operators perform their cognitive functions below their peak cognitive capacity level due to fatigue, stress, and boredom. Thus, there is a need to improve their cognitive functions during work. The goal of this paper is to present a psychophysiology training approach derived from cardiovascular response ...

  3. Polonium 210Po activities in human blood of patients with ischaemic heart disease from Gdansk in Poland

    International Nuclear Information System (INIS)

    Alicja Borylo; Bogdan Skwarzec; Grzegorz Romanczyk; Janusz Siebert

    2013-01-01

    The determination of polonium 210 Po in human blood samples is presented and discussed in this paper. The human blood samples were collected from patients of Medical University of Gdansk with ischaemic heart disease (morbus ischaemicus cordis, MIC). The polonium concentrations in analyzed human blood samples are very differentiated. 210 Po is of particular interest in public health and although is present in the environment in extremely low amounts, it is easily bioaccumulated to the human body. The study shows that the amount of 210 Po that is incorporated into the human body depends on the food habits and some difference in its levels could be observed between smokers and non-smokers. (author)

  4. Polonium 210Po activities in human blood of patients with ischaemic heart disease from Gdańsk in Poland.

    Science.gov (United States)

    Boryło, Alicja; Skwarzec, Bogdan; Romańczyk, Grzegorz; Siebert, Janusz

    The determination of polonium 210 Po in human blood samples is presented and discussed in this paper. The human blood samples were collected from patients of Medical University of Gdańsk with ischaemic heart disease ( morbus ischaemicus cordis , MIC ). The polonium concentrations in analyzed human blood samples are very differentiated. 210 Po is of particular interest in public health and although is present in the environment in extremely low amounts, it is easily bioaccumulated to the human body. The study shows that the amount of 210 Po that is incorporated into the human body depends on the food habits and some difference in its levels could be observed between smokers and non-smokers.

  5. Human Heart Pulse Wave Responses Measured Simultaneously at Several Sensor Placements by Two MR-Compatible Fibre Optic Methods

    Directory of Open Access Journals (Sweden)

    Teemu Myllylä

    2012-01-01

    Full Text Available This paper presents experimental measurements conducted using two noninvasive fibre optic methods for detecting heart pulse waves in the human body. Both methods can be used in conjunction with magnetic resonance imaging (MRI. For comparison, the paper also performs an MRI-compatible electrocardiogram (ECG measurement. By the simultaneous use of different measurement methods, the propagation of pressure waves generated by each heart pulse can be sensed extensively in different areas of the human body and at different depths, for example, on the chest and forehead and at the fingertip. An accurate determination of a pulse wave allows calculating the pulse transit time (PTT of a particular heart pulse in different parts of the human body. This result can then be used to estimate the pulse wave velocity of blood flow in different places. Both measurement methods are realized using magnetic resonance-compatible fibres, which makes the methods applicable to the MRI environment. One of the developed sensors is an extraordinary accelerometer sensor, while the other one is a more common sensor based on photoplethysmography. All measurements, involving several test patients, were performed both inside and outside an MRI room. Measurements inside the MRI room were conducted using a 3-Tesla strength closed MRI scanner in the Department of Diagnostic Radiology at the Oulu University Hospital.

  6. Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts

    NARCIS (Netherlands)

    van der Velden, J.; Klein, L. J.; Zaremba, R.; Boontje, N. M.; Huybregts, M. A.; Stooker, W.; Eijsman, L.; de Jong, J. W.; Visser, C. A.; Visser, F. C.; Stienen, G. J.

    2001-01-01

    During ischemia, the intracellular calcium and inorganic phosphate (P(i)) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the

  7. Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure.

    Science.gov (United States)

    Pandit, Sudip; Jo, Ji Yoon; Lee, Sang Ung; Lee, Young Jae; Lee, So Yeong; Ryu, Pan Dong; Lee, Jung Un; Kim, Hyun-Woo; Jeon, Byeong Hwa; Park, Jin Bong

    2015-08-01

    γ-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents (Itonic) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABAA receptors (GABAARs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of Itonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The Itonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced Itonic sensitivity to THIP argued for the decreased function of GABAAR δ subunits in HF, whereas similar Itonic sensitivity to benzodiazepines argued against the difference of γ2 subunit-containing GABAARs in SHAM and HF rats. HF Itonic attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal Itonic responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF Itonic attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABAARs function, the enhanced astroglial GABA uptake-induced attenuation of Itonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure. Copyright © 2015 the American Physiological Society.

  8. Effects of train noise and vibration on human heart rate during sleep: an experimental study.

    Science.gov (United States)

    Croy, Ilona; Smith, Michael G; Waye, Kerstin Persson

    2013-05-28

    Transportation of goods on railways is increasing and the majority of the increased numbers of freight trains run during the night. Transportation noise has adverse effects on sleep structure, affects the heart rate (HR) during sleep and may be linked to cardiovascular disease. Freight trains also generate vibration and little is known regarding the impact of vibration on human sleep. A laboratory study was conducted to examine how a realistic nocturnal railway traffic scenario influences HR during sleep. Case-control. Healthy participants. 24 healthy volunteers (11 men, 13 women, 19-28 years) spent six consecutive nights in the sleep laboratory. All participants slept during one habituation night, one control and four experimental nights in which train noise and vibration were reproduced. In the experimental nights, 20 or 36 trains with low-vibration or high-vibration characteristics were presented. Polysomnographical data and ECG were recorded. The train exposure led to a significant change of HR within 1 min of exposure onset (p=0.002), characterised by an initial and a delayed increase of HR. The high-vibration condition provoked an average increase of at least 3 bpm per train in 79% of the participants. Cardiac responses were in general higher in the high-vibration condition than in the low-vibration condition (p=0.006). No significant effect of noise sensitivity and gender was revealed, although there was a tendency for men to exhibit stronger HR acceleration than women. Freight trains provoke HR accelerations during sleep, and the vibration characteristics of the trains are of special importance. In the long term, this may affect cardiovascular functioning of persons living close to railways.

  9. Increased heart rate variability but normal resting metabolic rate in hypocretin/orexin-deficient human narcolepsy.

    NARCIS (Netherlands)

    Fronczek, R.; Overeem, S.; Reijntjes, R.; Lammers, G.J.; Dijk, J.G.M.; Pijl, H.

    2008-01-01

    STUDY OBJECTIVES: We investigated autonomic balance and resting metabolic rate to explore their possible involvement in obesity in hypocretin/orexin-deficient narcoleptic subjects. METHODS: Resting metabolic rate (using indirect calorimetry) and variability in heart rate and blood pressure were

  10. Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction.

    Science.gov (United States)

    Xue, Xiaodong; Liu, Yu; Zhang, Jian; Liu, Tao; Yang, Zhonglu; Wang, Huishan

    2015-01-01

    Objectives. Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

  11. The characterisation of blood rotation in a human heart chamber based on statistical analysis of vorticity maps

    Science.gov (United States)

    Wong, Kelvin K. L.; Kelso, Richard M.; Worthley, Stephen G.; Sanders, Prashanthan; Mazumdar, Jagannath; Abbott, Derek

    2008-12-01

    Modelling of non-stationary cardiac structures is complicated by the complexity of their intrinsic and extrinsic motion. The first known study of haemodynamics due to the beating of heart was made by Leonardo Da Vinci, giving the idea of fluid-solid interaction by describing how vortices develop during cardiac structural interaction with the blood. Heart morphology affects in changes of cardio dynamics during the systolic and diastolic phrases. In a chamber of the heart, vortices are discovered to exist as the result of the unique morphological changes of the cardiac chamber wall by using flow-imaging techniques such as phase contrast magnetic resonance imaging. The first part of this paper attempts to quantify vortex characteristics by means of calculating vorticity numerically and devising two dimensional vortical flow maps. The technique relies on determining the properties of vorticity using a statistical quantification of the flow maps and comparison of these quantities based on different scenarios. As the characteristics of our vorticity maps vary depending on the phase of a cardiac cycle, there is a need for robust quantification method to analyse vorticity. In the second part of the paper, the approach is then utilised for examining vortices within the human right atrium. Our study has shown that a proper quantification of vorticity for the flow field can indicate the strength and number of vortices within a heart chamber.

  12. ALDH1A2 (RALDH2 genetic variation in human congenital heart disease

    Directory of Open Access Journals (Sweden)

    Mesquita Sonia MF

    2009-11-01

    Full Text Available Abstract Background Signaling by the vitamin A-derived morphogen retinoic acid (RA is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2 is critical for cardiac development, we screened patients with congenital heart disease (CHDs for genetic variation at the ALDH1A2 locus. Methods One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430 at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay. Results We describe in Tetralogy of Fallot (TOF the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT design using single marker genotype, or haplotype information do not show differences between cases and controls. Conclusion In summary, our screen indicates that

  13. Heart Health - Brave Heart

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Brave Heart Past Issues / Winter 2009 Table of Contents For ... you can have a good life after a heart attack." Lifestyle Changes Surviving—and thriving—after such ...

  14. Human tumor cell proliferation evaluated using manganese-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Rod D Braun

    Full Text Available Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn(2+ [measured with manganese-enhanced MRI (MEMRI], is linked to proliferation rate in vitro.Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl(2 for one hour and then thoroughly washed. MEMRI R(1 values (longitudinal relaxation rates, which have a positive linear relationship with Mn(2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn(2+-induced increases in R(1 compared to cells not exposed to Mn(2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R(1 values and proliferation rate (p≤0.005, while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R(1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet.These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.

  15. Xe enhanced CT in the human newborn infant

    International Nuclear Information System (INIS)

    Fuse, Yozen; Nemoto, Yuko; Shimizu, Mitsumasa; Uga, Naoki; Tada, Hiroshi; Fujii, Toshi; Machida, Keiichi; Kikuchi, Hideo; Izumi, Shigemitsu.

    1990-01-01

    With a cranial computed tomography (CT) using stable xenon gas as a diffusible tracer, we measured regional cerebral blood flow (rCBF) in 6 newborn infants with a variety of neurological abnormalities. Gestational ages and birthweights were 35 to 43 weeks and 2436 to 3540 g, respectively. Four infants exhibited hypoxic-ischemic encephalopathy (HIE), one infant had subdural hemorrhage and the other one was the infant with hyponatremia. A baseline CT was done during denitrogenation by 100% oxygen breathing and then a mixture of 35% xenon and 65% oxygen was breathed for 6 minutes. Six scans were obtained during the inhalation period then the infant was returned to breathing 100% oxygen and additional 7 scans were taken. Four samples of arterial blood were collected every 2 minutes before and during inhalation of the xenon gas. A rCBF was calculated with the changes of Hounsfield units in brain tissue and arterial blood. Relatively high blood flows in the region of the basal nuclei as well as decreased flows in the occipital white matter were observed in the infants with HIE. In an infant with subdural hemorrhage, the blood flows were markedly reduced in the areas adjacent to the lesion, including the basal nuclei, and frontal white matter in the opposite hemisphere. Xenon-enhanced CT by inhaling low concentration of the xenon gas enables to measure rCBF in the human newborn infants without no obvious side effect. (author)

  16. Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

    Directory of Open Access Journals (Sweden)

    Matthew A Schechter

    Full Text Available The molecular differences between ischemic (IF and non-ischemic (NIF heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins and 823 phosphopeptides (corresponding to 400 proteins from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05 when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.

  17. The human heart and the circulatory system as an interesting interdisciplinary topic in lessons of physics and biology

    International Nuclear Information System (INIS)

    Volná, M; Látal, F; Kubínek, R; Richterek, L

    2014-01-01

    Many topics which are closely related can be found in the national curriculum of the Czech Republic for physics and biology. One of them is the heart and the circulatory system in the human body. This topic was examined cross curriculum, a teaching module was created and the topic was chosen for our research. The task was to determine if the students of bachelor study are aware of connections between physics and biology within this topic and whether we can help them effectively to describe the corresponding physics phenomena in the human body connected, for example, with a heart attack or with the measurement of blood pressure. In this paper, the heart and the circulatory system are presented as suitable topics for an interdisciplinary teaching module which includes both theoretical and experimental parts. The module was evaluated by a group of first-year undergraduate students of physics at the Faculty of Science, Palacký University. The acquired knowledge was compared with another control group through a test. The highest efficiency of the module was evaluated on the basis of questions that covered the calculation problems. (paper)

  18. Heart Attack Payment - National

    Data.gov (United States)

    U.S. Department of Health & Human Services — Payment for heart attack patients measure – national data. This data set includes national-level data for payments associated with a 30-day episode of care for heart...

  19. Heart Attack Payment - Hospital

    Data.gov (United States)

    U.S. Department of Health & Human Services — Payment for heart attack patients measure – provider data. This data set includes provider data for payments associated with a 30-day episode of care for heart...

  20. Heart Attack Payment - State

    Data.gov (United States)

    U.S. Department of Health & Human Services — Payment for heart attack patients measure – state data. This data set includes state-level data for payments associated with a 30-day episode of care for heart...

  1. A pilot investigation of the effect of extremely low frequency pulsed electromagnetic fields on humans' heart rate variability.

    Science.gov (United States)

    Baldi, Emilio; Baldi, Claudio; Lithgow, Brian J

    2007-01-01

    The question whether pulsed electromagnetic field (PEMF) can affect the heart rhythm is still controversial. This study investigates the effects on the cardiocirculatory system of ELF-PEMFs. It is a follow-up to an investigation made of the possible therapeutic effect ELF-PEMFs, using a commercially available magneto therapeutic unit, had on soft tissue injury repair in humans. Modulation of heart rate (HR) or heart rate variability (HRV) can be detected from changes in periodicity of the R-R interval and/or from changes in the numbers of heart-beat/min (bpm), however, R-R interval analysis gives only a quantitative insight into HRV. A qualitative understanding of HRV can be obtained considering the power spectral density (PSD) of the R-R intervals Fourier transform. In this study PSD is the investigative tool used, more specifically the low frequency (LF) PSD and high frequency (HF) PSD ratio (LF/HF) which is an indicator of sympatho-vagal balance. To obtain the PSD value, variations of the R-R time intervals were evaluated from a continuously recorded ECG. The results show a HR variation in all the subjects when they are exposed to the same ELF-PEMF. This variation can be detected by observing the change in the sympatho-vagal equilibrium, which is an indicator of modulation of heart activity. Variation of the LF/HF PSD ratio mainly occurs at transition times from exposure to nonexposure, or vice versa. Also of interest are the results obtained during the exposure of one subject to a range of different ELF-PEMFs. This pilot study suggests that a full investigation into the effect of ELF-PEMFs on the cardiovascular system is justified.

  2. Common variation in ISL1 confers genetic susceptibility for human congenital heart disease.

    Directory of Open Access Journals (Sweden)

    Kristen N Stevens

    Full Text Available Congenital heart disease (CHD is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1 is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant-common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations.

  3. Reconstruction and Visualization of Fiber and Laminar Structure in the Normal Human Heart from Ex Vivo DTMRI Data

    International Nuclear Information System (INIS)

    Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

    2006-01-01

    Background--The human heart is composed of a helical network of muscle fibers. These fibers are organized to form sheets that are separated by cleavage surfaces. This complex structure of fibers and sheets is responsible for the orthotropic mechanical properties of cardiac muscle. The understanding of the configuration of the 3D fiber and sheet structure is important for modeling the mechanical and electrical properties of the heart and changes in this configuration maybe of significant importance to understand the remodeling after myocardial infarction. Methods--Anisotropic least square filtering followed by fiber and sheet tracking techniques were applied to Diffusion Tensor Magnetic Resonance Imaging (DTMRI) data of the excised human heart. The fiber configuration was visualized by using thin tubes to increase 3-dimensional visual perception of the complex structure. The sheet structures were reconstructed from the DTMRI data, obtaining surfaces that span the wall from the endo- to the epicardium. All visualizations were performed using the high-quality ray-tracing software POV-Ray. Results--The fibers are shown to lie in sheets that have concave or convex transmural structure which correspond to histological studies published in the literature. The fiber angles varied depending on the position between the epi- and endocardium. The sheets had a complex structure that depended on the location within the myocardium. In the apex region the sheets had more curvature. Conclusions--A high-quality visualization algorithm applied to demonstrated high quality DTMRI data is able to elicit the comprehension of the complex 3 dimensional structure of the fibers and sheets in the heart

  4. Myocardial blood flow and its transit time, oxygen utilization, and efficiency of highly endurance-trained human heart.

    Science.gov (United States)

    Heinonen, Ilkka; Kudomi, Nobuyuki; Kemppainen, Jukka; Kiviniemi, Antti; Noponen, Tommi; Luotolahti, Matti; Luoto, Pauliina; Oikonen, Vesa; Sipilä, Hannu T; Kopra, Jaakko; Mononen, Ilkka; Duncker, Dirk J; Knuuti, Juhani; Kalliokoski, Kari K

    2014-07-01

    Highly endurance-trained athlete's heart represents the most extreme form of cardiac adaptation to physical stress, but its circulatory alterations remain obscure. In the present study, myocardial blood flow (MBF), blood mean transit time (MTT), oxygen extraction fraction (OEF) and consumption (MVO2), and efficiency of cardiac work were quantified in highly trained male endurance athletes and control subjects at rest and during supine cycling exercise using [(15)O]-labeled radiotracers and positron emission tomography. Heart rate and MBF were lower in athletes both at rest and during exercise. OEF increased in response to exercise in both groups, but was higher in athletes (70 ± 21 vs. 63 ± 11 % at rest and 86 ± 13 vs. 73 ± 10 % during exercise). MTT was longer and vascular resistance higher in athletes both at rest and during exercise, but arterial content of 2,3-diphosphoglycerate (oxygen affinity) was unchanged. MVO2 per gram of myocardium trended (p = 0.08) lower in athletes both at rest and during exercise, while myocardial efficiency of work and MVO2 per beat were not different between groups. Arterial levels of free fatty acids were ~twofold higher in athletes likely leading to higher myocardial fatty acid oxidation and hence oxygen cost, which may have blunted the bradycardia-induced decrease in MVO2. Finally, the observed group differences in MBF, OEF, MTT and vascular resistance remained significant also after they were controlled for differences in MVO2. In conclusion, in highly endurance-trained human heart, increased myocardial blood transition time enables higher oxygen extraction levels with a lower myocardial blood flow and higher vascular resistance. These physiological adaptations to exercise training occur independently of the level of oxygen consumption and together with training-induced bradycardia may serve as mechanisms to increase functional reserve of the human heart.

  5. Cardioprotection of Electroacupuncture for Enhanced Recovery after Surgery on Patients Undergoing Heart Valve Replacement with Cardiopulmonary Bypass: A Randomized Control Clinical Trial

    Directory of Open Access Journals (Sweden)

    Fangxiang Zhang

    2017-01-01

    Full Text Available We attempted to investigate cardioprotection of electroacupuncture (EA for enhanced recovery after surgery on patients undergoing heart valve replacement with cardiopulmonary bypass. Forty-four patients with acquired heart valve replacement were randomly allocated to the EA group or the control group. Patients in the EA group received EA stimulus at bilateral Neiguan (PC6, Ximen (PC4, Shenting (GV24, and Baihui (GV20 acupoints twenty minutes before anesthesia induction to the end of surgery. The primary end point was cardioprotection effect of electroacupuncture postoperatively and the secondary endpoints were quality of recovery and cognitive functioning postoperatively. The present study demonstrated that electroacupuncture reduced the occurrence of complications and played a role of cardioprotective effect on patients after heart valve replacement surgery with cardiopulmonary bypass, and it benefits patients more comfortable and contributes to recovery after surgery. This trial is registered with ChiCTR-IOC-16009123.

  6. Bleeding-Heart Liberals and Hard-Hearted Conservatives: Subtle Political Dehumanization Through Differential Attributions of Human Nature and Human Uniqueness Traits

    Directory of Open Access Journals (Sweden)

    Jarret T. Crawford

    2013-10-01

    Full Text Available This research demonstrated that human nature (HN and human uniqueness (HU traits capture the content of Americans’ stereotypes about liberals and conservatives, respectively. Consistent with expectations derived from dehumanization theory, people more strongly associated HN traits with liberals than with conservatives, and more strongly associated HU traits with conservatives than with liberals. A trait × target ideology × perceiver ideology × trait valence interaction suggested that both liberals and conservatives more strongly associated their ingroup with stereotype-consistent positive traits, and their outgroup with stereotype-consistent negative traits. Mediation analyses revealed that outgroup antipathy, but not ingroup liking, explained the relationship between ideology and political outgroup dehumanization. Finally, humanness traits captured subtle differences in political stereotype content not captured with the warmth and competence dimensions derived from the stereotype content model. Together, these results indicate that differential attributions of HN and HU traits capture political stereotype content and function to subtly dehumanize one’s political opponents.

  7. Growth and remodeling play opposing roles during postnatal human heart valve development.

    Science.gov (United States)

    Oomen, Pim J A; Holland, Maria A; Bouten, Carlijn V C; Kuhl, Ellen; Loerakker, Sandra

    2018-01-19

    Tissue growth and remodeling are known to govern mechanical homeostasis in biological tissue, but their relative contributions to homeostasis remain unclear. Here, we use mechanical models, fueled by experimental findings, to demonstrate that growth and remodeling have different effects on heart valve stretch homeostasis during physiological postnatal development. Two developmental stages were considered: early-stage (from infant to adolescent) and late-stage (from adolescent to adult) development. Our models indicated that growth and remodeling play opposing roles in preserving tissue stretch and with time. During early-stage development, excessive tissue stretch was decreased by tissue growth and increased by remodeling. In contrast, during late-stage development tissue stretch was decreased by remodeling and increased by growth. Our findings contribute to an improved understanding of native heart valve adaptation throughout life, and are highly relevant for the development of tissue-engineered heart valves.

  8. Enhanced external counterpulsation for the treatment of stable angina and heart failure: a systematic review and economic analysis.

    Science.gov (United States)

    McKenna, C; McDaid, C; Suekarran, S; Hawkins, N; Claxton, K; Light, K; Chester, M; Cleland, J; Woolacott, N; Sculpher, M

    2009-04-01

    To determine the clinical effectiveness and cost-effectiveness of enhanced external counterpulsation (EECP) compared with usual care and placebo for refractory stable angina and heart failure, and to undertake analyses of the expected value of information to assess the potential value of future research on EECP. Major electronic databases were searched between November 2007 and March 2008. A systematic review of the literature was undertaken and a decision model developed to compare EECP treatment with no treatment in adults with chronic stable angina. Five studies were included in the review. In the Multicenter Study of Enhanced External Counterpulsation (MUST-EECP), time to greater than or equal to 1-mm ST segment depression (exercise-induced ischaemia) was statistically significantly improved in the EECP group compared with the control group (sham EECP), mean difference (MD) 41 seconds [95% confidence interval (CI) 9.10-73.90]. However, there was no statistically significant difference between the EECP and control groups in the change in exercise duration from baseline to end of treatment, self-reported angina episodes or daily nitroglycerin use, and the clinical significance of the limited benefits was unclear. There was also a lack of data on long-term outcomes. There were more withdrawals due to adverse events in the EECP group than in the control group, as well as a greater proportion of patients with adverse events [relative risk (RR) 2.13, 95% CI 1.35-3.38]. The three non-randomised studies compared EECP with elective percutaneous coronary intervention (PCI) and usual care. There was a high risk of selection bias in all three studies and the results should be treated with considerable caution. The study comparing an EECP registry with a PCI registry reported similar 1-year all-cause mortality in both groups. In the Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) trial, patients with heart failure were randomised to EECP or to usual care

  9. Effect of enhanced external counterpulsation therapy on myeloperoxidase in lowering cardiovascular events of patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Starry H. Rampengan

    2013-08-01

    Full Text Available Background: Chronic heart failure (CHF is a slowly progressive disease with high morbidity and mortality; therefore, the management using pharmacological treatments frequently fails to improve outcome. Enhanced external counterpulsation (EECP, a non-invasive treatment, may serve as alternative treatment for heart failure. This study was aimed to evaluate the influence of EECP on myeloperoxidase (MPO as inflammatory marker as well as cardiac events outcome.Methods: This was an open randomized controlled clinical trial on 66 CHF patients visiting several cardiovascular clinics in Manado between January-December 2012. The subjects were randomly divided into two groups, i.e. the group who receive EECP therapy and those who did not receive EECP therapy with 33 patients in each group. Myeloperoxidase (MPO as inflammatory marker was examined at baseline and after 6 months of observation. Cardiovascular events were observed as well after 6 months of observation. Unpaired t-test was use to analyze the difference of MPO between the two groups, and chi-square followed by calculation of relative risk were used for estimation of cardiovascular event outcomes.Results: MPO measurement at baseline and after 6 months in EECP group were 643.16 ± 239.40 pM and 422.31 ± 156.26 pM, respectively (p < 0.001. Whereas in non EECP group, the MPO values were 584.69 ± 281.40 pM and 517.64 ± 189.68 pM, repectively (p = 0.792. MPO reduction was observed in all patients of EECP group and in 13 patients (48% of non-EECP group (p < 0.001. Cardiovascular events were observed in 7 (21.21% and 15 (45.45% of patients in EECP and non-EECP groups, respectively (p = 0.037.Conclusion: EECP therapy significantly decreased the level of MPO as inflammatory marker and this decrease was correlated with the reduction of cardiovascular events in CHF patients. (Med J Indones. 2013;22:152-60. doi: 10.13181/mji.v22i3.584Keywords: CHF, cardiovascular events, EECP, myeloperoxidase

  10. Interactions between Activation and Repolarization Restitution Properties in the Intact Human Heart: In-Vivo Whole-Heart Data and Mathematical Description.

    Directory of Open Access Journals (Sweden)

    Michele Orini

    Full Text Available The restitution of the action potential duration (APDR and conduction velocity (CVR are mechanisms whereby cardiac excitation and repolarization adapt to changes in heart rate. They modulate the vulnerability to dangerous arrhythmia, but the mechanistic link between restitution and arrhythmogenesis remains only partially understood.This paper provides an experimental and theoretical study of repolarization and excitation restitution properties and their interactions in the intact human epicardium. The interdependence between excitation and repolarization dynamic is studied in 8 patients (14 restitution protocols, 1722 restitution curves undergoing global epicardial mapping with multi-electrode socks before open heart surgery. A mathematical description of the contribution of both repolarization and conduction dynamics to the steepness of the APDR slope is proposed.This study demonstrates that the APDR slope is a function of both activation and repolarization dynamics. At short cycle length, conduction delay significantly increases the APDR slope by interacting with the diastolic interval. As predicted by the proposed mathematical formulation, the APDR slope was more sensitive to activation time prolongation than to the simultaneous shortening of repolarization time. A steep APDR slope was frequently identified, with 61% of all cardiac sites exhibiting an APDR slope > 1, suggesting that a slope > 1 may not necessarily promote electrical instability in the human epicardium. APDR slope did not change for different activation or repolarization times, and it was not a function of local baseline APD. However, it was affected by the spatial organization of electrical excitation, suggesting that in tissue APDR is not a unique function of local electrophysiological properties. Spatial heterogeneity in both activation and repolarization restitution contributed to the increase in the modulated dispersion of repolarization, which for short cycle length was

  11. Heart MRI

    Science.gov (United States)

    Magnetic resonance imaging - cardiac; Magnetic resonance imaging - heart; Nuclear magnetic resonance - cardiac; NMR - cardiac; MRI of the heart; Cardiomyopathy - MRI; Heart failure - MRI; Congenital heart disease - MRI

  12. Evaluation of radiation dose in chest scan with enhanced dual-source computed tomography in children with congenital heart disease

    International Nuclear Information System (INIS)

    Hou Zhihui; Lu Bin; Tang Xiang; Han Lei

    2011-01-01

    Objective: To evaluate the radiation dose from enhanced dual-source computed Tomography (DSCT) scan on children with congenital heart disease (CHD). Methods: Seventy children with CHD, age from 1 month to 8 years old, were scanned with enhanced DSCT. Children were divided by age into 5 years old group. The differences among three groups were tested by F test. Then, the SNK test was used to compare the difference between each group. Multiple linear regression analysis was used to test the relationship of dose length product (DLP) with the age, weight, voltage, current, pitch and scan sheet. Results: The average value of DLP was (144.46± 74.07) mGy·cm for all the 70 cases, and that of effective does (ED) was (4.68±2.34) mSv. There were significant differences of DLP among the 3 groups [ 5 years (208.00±73.87) mGy · cm, F=8.26, P=0.0009]. The SNK test showed statistical differences of DLP between 5 years old group (q=5.21, 6.52, P=0.009, 0.004). The difference of DLP between 1-5 years old group and > 5 years old group did not reach significant (q=0.28, P=0.48). The differences of ED was not statistically significant among the three groups [ 5 years (3.74±1.33) mSv, F=0.54, P=0.59]. DLP was positively correlated with age (4.3 years, r=0.54186, P=0.0008), weight (12.1 kg, r=0.56371, P=0.0004), voltage [(95.48±6.99) kV, r=0.63269, P<0.01], current [(138.55±40.67) mA, r=0.79608, P< 0.0001] and scan sheet (236.10±46.51, r=0.72192, P<0.01). DLP was negative correlated with pitch (0.48±0.03, r=-0.46693, P=0.0047). Conclusion: Higher DLP was observed in children over 1 year old under enhanced DSCT scan, but ED was not statistically significant among the three groups due to the higher K value in the children under 1 year old. (authors)

  13. Vortex ring behavior provides the epigenetic blueprint for the human heart.

    Science.gov (United States)

    Arvidsson, Per M; Kovács, Sándor J; Töger, Johannes; Borgquist, Rasmus; Heiberg, Einar; Carlsson, Marcus; Arheden, Håkan

    2016-02-26

    The laws of fluid dynamics govern vortex ring formation and precede cardiac development by billions of years, suggesting that diastolic vortex ring formation is instrumental in defining the shape of the heart. Using novel and validated magnetic resonance imaging measurements, we show that the healthy left ventricle moves in tandem with the expanding vortex ring, indicating that cardiac form and function is epigenetically optimized to accommodate vortex ring formation for volume pumping. Healthy hearts demonstrate a strong coupling between vortex and cardiac volumes (R(2) = 0.83), but this optimized phenotype is lost in heart failure, suggesting restoration of normal vortex ring dynamics as a new, and possibly important consideration for individualized heart failure treatment. Vortex ring volume was unrelated to early rapid filling (E-wave) velocity in patients and controls. Characteristics of vortex-wall interaction provide unique physiologic and mechanistic information about cardiac diastolic function that may be applied to guide the design and implantation of prosthetic valves, and have potential clinical utility as therapeutic targets for tailored medicine or measures of cardiac health.

  14. Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models.

    Science.gov (United States)

    Deddens, Janine C; Sadeghi, Amir Hossein; Hjortnaes, Jesper; van Laake, Linda W; Buijsrogge, Marc; Doevendans, Pieter A; Khademhosseini, Ali; Sluijter, Joost P G

    2017-02-01

    Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the failing heart. With recent advances in both disease biology and cardiac tissue engineering, the translation of fundamental laboratory research toward the treatment of chronic heart failure patients becomes a more realistic option. Here, the current understanding of cardiac fibrosis and the great potential of tissue engineering are presented. Approaches using hydrogel-based tissue engineered heart constructs are discussed to contemplate key challenges for modeling tissue engineered cardiac fibrosis and to provide a future outlook for preclinical and clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Modeling the Human Scarred Heart In Vitro : Toward New Tissue Engineered Models

    NARCIS (Netherlands)

    Deddens, Janine C.; Sadeghi, Amir Hossein; Hjortnaes, Jesper; van Laake, Linda W.; Buijsrogge, Marc; Doevendans, Pieter A.; Khademhosseini, Ali; Sluijter, Joost P G

    2017-01-01

    Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An

  16. Decreased mitochondrial oxidative phosphorylation capacity in the human heart with left ventricular systolic dysfunction

    DEFF Research Database (Denmark)

    Stride, Nis; Larsen, Steen; Hey-Mogensen, Martin

    2013-01-01

    Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could...

  17. Variation in tissue outcome of ovine and human engineered heart valve constructs : relevance for tissue engineering

    NARCIS (Netherlands)

    Geemen, van D.; Driessen - Mol, A.; Grootzwagers, L.G.M.; Soekhradj - Soechit, R.S.; Riem Vis, P.W.; Baaijens, F.P.T.; Bouten, C.V.C.

    AIM: Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and

  18. Hydrocortisone at stress-associated concentrations helps maintain human heart rate variability during subsequent endotoxin challenge.

    Science.gov (United States)

    Rassias, Athos J; Guyre, Paul M; Yeager, Mark P

    2011-12-01

    We evaluated the differential impact of stress-associated vs high pharmacologic concentrations of hydrocortisone pretreatment on heart rate variability (HRV) during a subsequent systemic inflammatory stimulus. Healthy volunteers were randomized to receive placebo (Control) and hydrocortisone at 1.5 μg/kg per minute (STRESS) or at 3.0 μg/kg per minute (PHARM) as a 6-hour infusion. The STRESS dose was chosen to replicate the condition of physiologic adrenal cortical output during acute systemic stress. The PHARM dose was chosen to induce a supraphysiologic concentration of cortisol. The next day, all subjects received 2 ng/kg Escherichia coli endotoxin (lipopolysaccharide). Heart rate variability was analyzed with the statistic approximate entropy (ApEn). A lower ApEn correlates with decreased HRV. At the 3-hour nadir, the decrease in ApEn in the STRESS group was significantly less compared to placebo (P statistically different. We also found that the maximal decrease in ApEn preceded maximal increase in heart rate in all groups. The decrease in R-R interval was maximal at 4 hours, whereas the ApEn nadir was 1 hour earlier at 3 hours. Pretreatment with a stress dose of hydrocortisone but not a higher pharmacologic dose maintained a significantly higher ApEn after endotoxin exposure when compared to a placebo. In addition, decreases in ApEn preceded increases in heart rate. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Seasonal superoxide overproduction and endothelial activation in guinea-pig heart; seasonal oxidative stress in rats and humans.

    Science.gov (United States)

    Konior, Anna; Klemenska, Emilia; Brudek, Magdalena; Podolecka, Ewa; Czarnowska, Elżbieta; Beręsewicz, Andrzej

    2011-04-01

    Seasonality in endothelial dysfunction and oxidative stress was noted in humans and rats, suggesting it is a common phenomenon of a potential clinical relevance. We aimed at studying (i) seasonal variations in cardiac superoxide (O(2)(-)) production in rodents and in 8-isoprostane urinary excretion in humans, (ii) the mechanism of cardiac O(2)(-) overproduction occurring in late spring/summer months in rodents, (iii) whether this seasonal O(2)(-)-overproduction is associated with a pro-inflammatory endothelial activation, and (iv) how the summer-associated changes compare to those caused by diabetes, a classical cardiovascular risk factor. Langendorff-perfused guinea-pig and rat hearts generated ~100% more O(2)(-), and human subjects excreted 65% more 8-isoprostane in the summer vs. other seasons. Inhibitors of NADPH oxidase, xanthine oxidase, and NO synthase inhibited the seasonal O(2)(-)-overproduction. In the summer vs. other seasons, cardiac NADPH oxidase and xanthine oxidase activity, and protein expression were increased, the endothelial NO synthase and superoxide dismutases were downregulated, and, in guinea-pig hearts, adhesion molecules upregulation and the endothelial glycocalyx destruction associated these changes. In guinea-pig hearts, the summer and a streptozotocin-induced diabetes mediated similar changes, yet, more severe endothelial activation associated the diabetes. These findings suggest that the seasonal oxidative stress is a common phenomenon, associated, at least in guinea-pigs, with the endothelial activation. Nonetheless, its biological meaning (regulatory vs. deleterious) remains unclear. Upregulated NADPH oxidase and xanthine oxidase and uncoupled NO synthase are the sources of the seasonal O(2)(-)-overproduction. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

    International Nuclear Information System (INIS)

    Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

    2009-01-01

    The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

  1. Reconstruction and Visualization of Fiber and Laminar Structure inthe Normal Human Heart from Ex Vivo DTMRI Data

    Energy Technology Data Exchange (ETDEWEB)

    Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

    2006-12-18

    Background - The human heart is composed of a helicalnetwork of muscle fibers. These fibers are organized to form sheets thatare separated by cleavage surfaces. This complex structure of fibers andsheets is responsible for the orthotropic mechanical properties ofcardiac muscle. The understanding of the configuration of the 3D fiberand sheet structure is important for modeling the mechanical andelectrical properties of the heart and changes in this configuration maybe of significant importance to understand the remodeling aftermyocardial infarction.Methods - Anisotropic least square filteringfollowed by fiber and sheet tracking techniques were applied to DiffusionTensor Magnetic Resonance Imaging (DTMRI) data of the excised humanheart. The fiber configuration was visualized by using thin tubes toincrease 3-dimensional visual perception of the complex structure. Thesheet structures were reconstructed from the DTMRI data, obtainingsurfaces that span the wall from the endo- to the epicardium. Allvisualizations were performed using the high-quality ray-tracing softwarePOV-Ray. Results - The fibers are shown to lie in sheets that haveconcave or convex transmural structure which correspond to histologicalstudies published in the literature. The fiber angles varied depending onthe position between the epi- and endocardium. The sheets had a complexstructure that depended on the location within the myocardium. In theapex region the sheets had more curvature. Conclusions - A high-qualityvisualization algorithm applied to demonstrated high quality DTMRI datais able to elicit the comprehension of the complex 3 dimensionalstructure of the fibers and sheets in the heart.

  2. Anizotropy characteristics of the left ventricle false chordae tendineae as one of varieties of myoendocardial formations of the human heart

    Science.gov (United States)

    Gavrylyak, M. S.; Malyk, Yu. Yu.; Tsyhykalo, O. V.; Semeniuk, T. O.; Penteleichuk, N. P.; Burkovets, D. N.; Yermolenko, S. B.

    2018-01-01

    The morphological and anizotropy characteristics of the left ventricle false chordae tendineae of human heart in the aspect of their anisotropic properties using spectroscopic-polarization methods was studied. There are given the results of statistical correlation structure of the spectral dependence of the two-dimensional Mueller matrix elements and phase shifts of histological sections of different morphological structure and physiological state. The relationship between the distribution of orientations of the optical axes birefringent miozyn fibrils with a set of statistical moments that characterize the distributions of Mueller matrix elements in different spectral ranges and half-width corresponding autocorrelation functions are established.

  3. Hypoxia changes the expression of the epidermal growth factor (EGF) system in human hearts and cultured cardiomyocytes

    DEFF Research Database (Denmark)

    Munk, Mathias; Memon, Ashfaque Ahmed; Goetze, Jens Peter

    2012-01-01

    by treatment with trastuzumab (20 nM). This resulted in inhibition of cardiomyocyte proliferation, but interestingly only in hypoxic cells. Co-treatment of HL-1 cells with HB-EGF (10 nM) but not with NRG-1 (5 ng/ml) rescued the cardiomyocytes from HER2 inhibition. HL-1 cardiomyocytes exposed to hypoxia...... revealed nuclear translocation of activated MAPK and the activity of this downstream signaling molecule was decreased by HER2 inhibition (20 nM trastuzumab), and re-established by HB-EGF (10 nM). CONCLUSIONS/SIGNIFICANCE: Hypoxia in the human heart alters the expression of the EGF system. Mimicking the HER...

  4. Political Minimalism and Social Debates: The Case of Human-Enhancement Technologies.

    Science.gov (United States)

    Rodríguez-Alcázar, Javier

    2017-09-01

    A faulty understanding of the relationship between morality and politics encumbers many contemporary debates on human enhancement. As a result, some ethical reflections on enhancement undervalue its social dimensions, while some social approaches to the topic lack normative import. In this essay, I use my own conception of the relationship between ethics and politics, which I call "political minimalism," in order to support and strengthen the existing social perspectives on human-enhancement technologies.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Y. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China); Liu, B. [Department of Pathology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei (China); Wang, H.P. [Department of Histology and Embryology, Hebei North University, Zhangjiakou, Hebei (China); Zhang, L. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China)

    2016-05-31

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Science.gov (United States)

    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 iso-PGF2α (P < 0.05). Inhibition of CYP epoxygenases with MS-PPOH attenuated CRH (P < 0.05). Ischemia caused a decrease in mid-chain HETEs (5-, 11-, 12-, 15-HETEs P < 0.05) and HODEs (P < 0.05). These data demonstrate that vascular endothelial overexpression of CYP2J2, through changing the oxylipin profiles, enhances CRH. Inhibition of CYP epoxygenases decreases CRH, whereas inhibition of ω-hydroxylases enhances CRH. PMID:28328948

  8. Evaluation of methods for MR imaging of human right ventricular heart volumes and mass

    International Nuclear Information System (INIS)

    Jauhiainen, T.; Jaervinen, V.M.; Hekali, P.E.

    2002-01-01

    Purpose: To assess the utility of two different imaging directions in the evaluation of human right ventricular (RV) heart volumes and mass with MR imaging; to compare breath-hold vs. non-breath-hold imaging in volume analysis; and to compare turbo inversion recovery imaging (TIR) with gradient echo imaging in RV mass measurement. Material and Methods: We examined 12 healthy volunteers (age 27-59 years). Breath-hold gradient echo MR imaging was performed in two imaging planes: 1) perpendicular to the RV inflow tract (RVIT view), and 2) in the transaxial view (TA view). The imaging was repeated in the TA view while the subjects were breathing freely. To analyze RV mass using TIR images, the RV was again imaged at end-diastole using the two views. The RV end-diastolic cavity (RVEDV) and muscle volume as well as end-systolic cavity volume (RVESV) were determined with the method of discs. All measurements were done blindly twice to assess repeatability of image analysis. To assess reproducibility of the measurements, 6 of the subjects were imaged twice at an interval of 5-9 weeks. Results: RVEDV averaged 133.2 ml, RVESV 61.5 ml and the RVmass 46.2 g in the RVIT view and 119.9 ml, 56.9 ml and 38.3 g in the TA view, respectively. The volumes obtained with breath-holding were slightly but not significantly smaller than the volumes obtained during normal breathing. There were no marked differences in the RV muscle mass obtained with gradient echo imaging compared to TIR imaging in either views. Repeatability of volume analysis was better in TA than RVIT view: the mean differences were 0.7±4.0 ml and 5.4±14.0 ml in end-diastole and 1.6±3.1 ml and 1.5±13.9 ml in end-systole, respectively. Repeatability of mass analysis was good in both TIR and cine images in the RVIT view but slightly better in TIR images: 0.5±2.4 g compared to 0.8±2.9 g in cine images. Reproducibility of imaging was good, mean differences for RVEDV and RVESV were 1.0±4.8 ml and 0.8±2.8 ml

  9. The relationship between the parameters (Heart rate, Ejection fraction and BMI) and the maximum enhancement time of ascending aorta

    International Nuclear Information System (INIS)

    Jang, Young Ill; June, Woon Kwan; Dong, Kyeong Rae

    2007-01-01

    In this study, Bolus Tracking method was used to investigate the parameters affecting the time when contrast media is reached at 100 HU (T 100 ) and studied the relationship between parameters and T 100 because the time which is reached at aorta through antecubital vein after injecting contrast media is different from person to person. Using 64 MDCT, Cadiac CT, the data were obtained from 100 patients (male: 50, female: 50, age distribution: 21⁓81, average age: 57.5) during July and September, 2007 by injecting the contrast media at 4 ml∙sec -1 through their antecubital vein except having difficulties in stopping their breath and having arrhythmia. Using Somatom Sensation Cardiac 64 Siemens, patients’ height and weight were measured to know their mean Heart rate and BMI. Ejection Fraction was measured using Argus Program at Wizard Workstation. Variances of each parameter were analyzed depending on T 100 ’s variation with multiple comparison and the correlation of Heart rate, Ejection Fraction and BMI were analyzed, as well. According to T 100 ’s variation caused by Heart rate, Ejection Fraction and BMI variations, the higher patients’ Heart Rate and Ejection Fraction were, the faster T 100 ’s variations caused by Heart Rate and Ejection Fraction were. The lower their Heart Rate and Ejection Fraction were, the slower T 100 ’s variations were, but T 100 ’s variations caused by BMI were not affected. In the correlation between T 100 and parameters, Heart Rate (p⁄0.01) and Ejection Fraction (p⁄0.05) were significant, but BMI was not significant (p¤0.05). In the Heart Rate, Ejection Fraction and BMI depending on Fast (17 sec and less), Medium (18⁓21 sec), Slow (22 sec and over) Heart Rate was significant at Fast and Slow and Ejection Fraction was significant Fast and Slow as well as Medium and Slow (p⁄0.05), but BMI was not statistically significant. Of the parameters (Heart Rate, Ejection Fraction and BMI) which would affect T 100 , Heart

  10. Gallium-67 imaging in human heart transplantation: correlation with endomyocardial biopsy

    International Nuclear Information System (INIS)

    Meneguetti, J.C.; Camargo, E.E.; Soares, J. Jr.

    1987-01-01

    Endomyocardial biopsy seems to be the most accurate method to use for diagnosis and follow-up of acute rejection of the transplanted heart. This investigation compared a noninvasive procedure, gallium-67 imaging, with endomyocardial biopsy in the detection of acute rejection in heart transplantation. Seven male patients (aged 41 to 54 years) sequentially had 46 gallium-67 scintigrams and 46 endomyocardial biopsies between 1 week and 8 months after transplantation. Both studies were obtained in the same day, 48 hours after the administration of an intravenous injection of gallium-67 citrate. Cardiac uptake was graded as negative, mild, moderate, and marked according to an increasing count ratio with rib and sternal uptakes. Histologic findings were graded as negative, mild acute rejection, moderate acute rejection, severe acute rejection, resolving rejection, and nonspecific reaction. Negative biopsies were not found with moderate uptake, and neither moderate nor severe acute rejection were found with negative scintigrams. Imaging sensitivity was 83% with 17% false negatives and 9% false positives. Of seven studies with moderate uptake, five showed moderate acute rejection, and the patients had specific therapy with a decline in uptake, which correlated with resolving rejection. It is conceivable that in the future this technique may be used as a screening procedure for sequential endomyocardial biopsies in the follow-up of heart transplant patients

  11. Identification of Enhancers In Human: Advances In Computational Studies

    KAUST Repository

    Kleftogiannis, Dimitrios A.

    2016-01-01

    Finally, we take a step further by developing a novel feature selection method suitable for defining a computational framework capable of analyzing the genomic content of enhancers and reporting cell-line specific predictive signatures.

  12. The Heart of Coaching

    Science.gov (United States)

    Docheff, Dennis M.; Gerdes, Dan

    2015-01-01

    This article challenges coaches to address the more personal, human elements of coaching--the HEART of coaching. While there is much research on numerous aspects of coaching, this article provides ideas that make a lasting impact on the hearts of athletes. Using HEART as an acronym, five elements of effective coaching are presented: Humility,…

  13. Coping with continuous human disturbance in the wild: insights from penguin heart rate response to various stressors.

    Science.gov (United States)

    Viblanc, Vincent A; Smith, Andrew D; Gineste, Benoit; Groscolas, René

    2012-07-11

    A central question for ecologists is the extent to which anthropogenic disturbances (e.g. tourism) might impact wildlife and affect the systems under study. From a research perspective, identifying the effects of human disturbance caused by research-related activities is crucial in order to understand and account for potential biases and derive appropriate conclusions from the data. Here, we document a case of biological adjustment to chronic human disturbance in a colonial seabird, the king penguin (Aptenodytes patagonicus), breeding on remote and protected islands of the Southern ocean. Using heart rate (HR) as a measure of the stress response, we show that, in a colony with areas exposed to the continuous presence of humans (including scientists) for over 50 years, penguins have adjusted to human disturbance and habituated to certain, but not all, types of stressors. When compared to birds breeding in relatively undisturbed areas, birds in areas of high chronic human disturbance were found to exhibit attenuated HR responses to acute anthropogenic stressors of low-intensity (i.e. sounds or human approaches) to which they had been subjected intensely over the years. However, such attenuation was not apparent for high-intensity stressors (i.e. captures for scientific research) which only a few individuals experience each year. Habituation to anthropogenic sounds/approaches could be an adaptation to deal with chronic innocuous stressors, and beneficial from a research perspective. Alternately, whether penguins have actually habituated to anthropogenic disturbances over time or whether human presence has driven the directional selection of human-tolerant phenotypes, remains an open question with profound ecological and conservation implications, and emphasizes the need for more knowledge on the effects of human disturbance on long-term studied populations.

  14. Coping with continuous human disturbance in the wild: insights from penguin heart rate response to various stressors

    Directory of Open Access Journals (Sweden)

    Viblanc Vincent A

    2012-07-01

    Full Text Available Abstract Background A central question for ecologists is the extent to which anthropogenic disturbances (e.g. tourism might impact wildlife and affect the systems under study. From a research perspective, identifying the effects of human disturbance caused by research-related activities is crucial in order to understand and account for potential biases and derive appropriate conclusions from the data. Results Here, we document a case of biological adjustment to chronic human disturbance in a colonial seabird, the king penguin (Aptenodytes patagonicus, breeding on remote and protected islands of the Southern ocean. Using heart rate (HR as a measure of the stress response, we show that, in a colony with areas exposed to the continuous presence of humans (including scientists for over 50 years, penguins have adjusted to human disturbance and habituated to certain, but not all, types of stressors. When compared to birds breeding in relatively undisturbed areas, birds in areas of high chronic human disturbance were found to exhibit attenuated HR responses to acute anthropogenic stressors of low-intensity (i.e. sounds or human approaches to which they had been subjected intensely over the years. However, such attenuation was not apparent for high-intensity stressors (i.e. captures for scientific research which only a few individuals experience each year. Conclusions Habituation to anthropogenic sounds/approaches could be an adaptation to deal with chronic innocuous stressors, and beneficial from a research perspective. Alternately, whether penguins have actually habituated to anthropogenic disturbances over time or whether human presence has driven the directional selection of human-tolerant phenotypes, remains an open question with profound ecological and conservation implications, and emphasizes the need for more knowledge on the effects of human disturbance on long-term studied populations.

  15. Heart murmurs

    Science.gov (United States)

    Chest sounds - murmurs; Heart sounds - abnormal; Murmur - innocent; Innocent murmur; Systolic heart murmur; Diastolic heart murmur ... The heart has 4 chambers: Two upper chambers (atria) Two lower chambers (ventricles) The heart has valves that close ...

  16. 3D Whole-Heart Coronary MR Angiography at 1.5T in Healthy Volunteers: Comparison between Unenhanced SSFP and Gd-Enhanced FLASH Sequences

    International Nuclear Information System (INIS)

    Gweon, Hye Mi; Kim, Sang Jin; Lee, Sang Min; Hong, Yoo Jin; Kim, Tae Hoon

    2011-01-01

    To validate the optimal cardiac phase and appropriate acquisition window for three-dimensional (3D) whole-heart coronary magnetic resonance angiography (MRA) with a steady-state free precession (SSFP) sequence, and to compare image quality between SSFP and Gd-enhanced fast low-angle shot (FLASH) MR techniques at 1.5 Tesla (T). Thirty healthy volunteers (M:F 25:5; mean age, 35 years; range, 24-54 years) underwent a coronary MRA at 1.5T. 3D whole-heart coronary MRA with an SSFP was performed at three different times: 1) at end-systole with a narrow (120-msec) acquisition window (ESN), 2) mid-diastole with narrow acquisition (MDN); and 3) mid-diastole with wide (170-msec) acquisition (MDW). All volunteers underwent a contrast enhanced coronary MRA after undergoing an unenhanced 3D true fast imaging with steady-state precession (FISP) MRA three times. A contrast enhanced coronary MRA with FLASH was performed during MDN. Visibility of the coronary artery and image quality were evaluated for 11 segments, as suggested by the American Heart Association. Image quality was scored by a five-point scale (1 = not visible to 5 = excellent). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated at the proximal coronary arteries. The SSFP sequence rendered higher visibility coronary segments, higher image quality, as well as higher SNR and CNR than the Gd-enhanced FLASH technique at 1.5T (p < 0.05). The visibility of coronary segments, image quality, SNR and CNR in the ESN, MDN and MDW with SSFP sequence did not differ significantly. An SSFP sequence provides an excellent method for the 3D whole-heart coronary MRA at 1.5T. Contrast enhanced coronary MRA using the FLASH sequence does not help improve the visibility of coronary segments, image quality, SNR or CNR on the 3D whole-heart coronary MRA.

  17. Noradrenergic enhancement of associative fear memory in humans

    NARCIS (Netherlands)

    Soeter, M.; Kindt, M.

    2011-01-01

    Ample evidence in animals and humans supports the noradrenergic modulation in the formation of emotional memory. However, in humans the effects of stress on emotional memory are traditionally investigated by declarative memory tests (e.g., recall, recognition) for non-associative emotional stimuli

  18. Engineering Substantially Prolonged Human Lifespans: Biotechnological Enhancement and Ethics

    NARCIS (Netherlands)

    Derkx, P.H.J.M.

    2006-01-01

    Substantial extension of the human lifespan has recently become a subject of lively debate. One reason for this is the completion in 2001 of the Human Genome Project and the experimental avenues for biogerontological research it has opened. Another is recent theoretical progress in biogerontology.

  19. Enhancement of human capital assets role in current economic situation

    Directory of Open Access Journals (Sweden)

    Pechenaia Liudmila Timofeevna

    2014-02-01

    Full Text Available The paper presents transformation of the notion “human capital assets” in economics. Methodical approaches to evaluation of human capital assets and involvement in innovation process. Generalization of theoretical overview data allows conclusion about strong interest to this economic category, testifying to good promise of this field development.

  20. Dehydration enhances pain-evoked activation in the human brain compared with rehydration.

    Science.gov (United States)

    Ogino, Yuichi; Kakeda, Takahiro; Nakamura, Koji; Saito, Shigeru

    2014-06-01

    Negative effects of dehydration on the human brain and cognitive function have been reported. In this study, we examined the effects of dehydration on pain thresholds and cortical activations in response to pain, compared with rehydration with an oral rehydration solution (ORS) by functional magnetic resonance imaging. Five healthy adult men were subjected to dehydration and rehydration on 2 different days. The condition on the first day was randomly assigned to each subject. They completed a 40-minute exercise protocol using a walking machine after 12 hours of fasting under both conditions. For rehydration, the subjects consumed up to 3000 mL ORS starting from the night before the test day. After exercise, a painful stimulus (cold pressor test) was applied to the subjects' medial forearm in a magnetic resonance imaging scanning gantry, and pain-evoked brain activation was analyzed. On the rehydration day, each of the subjects consumed an average of 2040 mL (range; 1800-2500 mL) ORS. Physiological data revealed that subjects when dehydrated lost more weight from exercise than subjects when rehydrated had a larger heart rate increase, a higher tympanic temperature, and a higher urine osmolality. Subjective data revealed that the subjects reported significantly stronger thirst while dehydrated than while rehydrated with ORS, although the levels of hunger and anxiety and mood did not significantly differ between conditions. The cold pressor test robustly activated the pain-related neural network, notably the anterior cingulate cortex, insula, and thalamus. Such activations in the dehydrated subjects were greater than those in the rehydrated subjects in terms of peak and cluster, accompanied by a decrease in pain threshold (P = 0.001). Our findings suggest that dehydration brings about increased brain activity related to painful stimuli together with enhanced thirst, whereas rehydration with ORS alleviates thirst and decreases brain activity related to painful stimuli.

  1. Human torso phantom for imaging of heart with realistic modes of cardiac and respiratory motion

    Science.gov (United States)

    Boutchko, Rostyslav; Balakrishnan, Karthikayan; Gullberg, Grant T; O& #x27; Neil, James P

    2013-09-17

    A human torso phantom and its construction, wherein the phantom mimics respiratory and cardiac cycles in a human allowing acquisition of medical imaging data under conditions simulating patient cardiac and respiratory motion.

  2. Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis

    Czech Academy of Sciences Publication Activity Database

    Melenovský, V.; Petrák, J.; Mráček, Tomáš; Beneš, J.; Borlaug, B. A.; Nůsková, Hana; Pluháček, T.; Špatenka, J.; Kovalčíková, Jana; Drahota, Zdeněk; Kautzner, J.; Pirk, J.; Houštěk, Josef

    2017-01-01

    Roč. 19, č. 4 (2017), s. 522-530 ISSN 1388-9842 R&D Projects: GA ČR(CZ) GB14-36804G; GA MZd(CZ) NT14050; GA MŠk(CZ) LQ1604; GA MZd NT14250; GA MŠk(CZ) ED1.1.00/02.0109; GA MZd(CZ) NV16-27496A Institutional support: RVO:67985823 Keywords : heart failure * mitochondria * iron deficiency * bioenergetics * metabolism * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 6.968, year: 2016

  3. Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure.

    Science.gov (United States)

    Marques, Francine Z; Prestes, Priscilla R; Byars, Sean G; Ritchie, Scott C; Würtz, Peter; Patel, Sheila K; Booth, Scott A; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P; Curl, Claire L; Bell, James R; Wai, Bryan; Srivastava, Piyush M; Kangas, Antti J; Soininen, Pasi; Ruohonen, Saku; Kähönen, Mika; Lehtimäki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E; Lewandowski, Paul A; Delbridge, Lea M; Burrell, Louise M; Inouye, Michael; Harrap, Stephen B; Charchar, Fadi J

    2017-06-14

    Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2 -knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2 -knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis -eQTL for LCN2 expression. Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  4. Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

    Science.gov (United States)

    Delgado, Nathalie T. B.; Rouver, Wender do N.; Freitas-Lima, Leandro C.; de Paula, Tiago D.-C.; Duarte, Andressa; Silva, Josiane F.; Lemos, Virgínia S.; Santos, Alexandre M. C.; Mauad, Helder; Santos, Roger L.; Moysés, Margareth R.

    2017-01-01

    Decline in estrogen levels promotes endothelial dysfunction and, consequently, the most prevalent cardiovascular diseases in menopausal women. The use of natural therapies such as pomegranate can change these results. Pomegranate [Punica granatum L. (Punicaceae)] is widely used as a phytotherapeutic agent worldwide, including in Brazil. We hypothesized that treatment with pomegranate hydroalcoholic extract (PHE) would improve coronary vascular reactivity and cardiovascular parameters. At the beginning of treatment, spontaneously hypertensive female rats were divided into Sham and ovariectomized (OVX) groups, which received pomegranate extract (PHE) (250 mg/kg) or filtered water (V) for 30 days by gavage. Systolic blood pressure was measured by tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed by Langendorff retrograde perfusion technique. A dose-response curve for bradykinin was performed, followed by L-NAME inhibition. The protein expression of p-eNOS Ser1177, p-eNOS Thr495, total eNOS, p-AKT Ser473, total AKT, SOD-2, and catalase was quantified by Western blotting. The detection of coronary superoxide was performed using the protocol of dihydroethidium (DHE) staining Plasma nitrite measurement was analyzed by Griess method. Systolic blood pressure increased in both Sham-V and OVX-V groups, whereas it was reduced after treatment in Sham-PHE and OVX-PHE groups. The baseline coronary perfusion pressure was reduced in the Sham-PHE group. The relaxation was significantly higher in the treated group, and L-NAME attenuated the relaxation in all groups. The treatment has not changed p-eNOS (Ser1177), total eNOS, p-AKT (Ser473) and total AKT in any groups. However, in Sham and OVX group the treatment reduced the p-eNOS (Thr495) and SOD-2. The ovariectomy promoted an increasing in the superoxide anion levels and the treatment was able to prevent this elevation and reducing oxidative stress. Moreover, the treatment

  5. Enhanced Detection of Human Plasma Proteins on Nanostructured Silver Surfaces

    Directory of Open Access Journals (Sweden)

    Zuzana Orságová Králová

    2013-08-01

    enhancement factor of 3.6×102 was achieved for a band with a Raman shift of 2104cm‐1 for globulin deposited onto silver nanostructured film on unpolished stainless steel substrate. The detection limit was 400g/mL. Plasma or serum could present a preferable material for non‐ invasive cancer disease diagnosis using the SERS method.

  6. Human Cognitive Enhancement Ethical Implications for Airman-Machine Teaming

    Science.gov (United States)

    2017-04-06

    involved with memory, emotion , and reasoning which can lead to improved task design and decision support systems. • Training efficiency: enabling...Kraemer, Felicitas. 2011. "Authenticity Anyone? The Enhancement of Emotions via Neuro- Psychopharmascology." Neuroethics (Springer) (4): 51-64...Impact Emerging Technology - What You Need to Know: Definitions, Adoptions, Impact, Benefits, Maturity , Vendors. LaVergne, Tennessee, USA: Lightning

  7. Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases

    Directory of Open Access Journals (Sweden)

    Jianhong Lu

    2017-08-01

    Full Text Available Coronary heart disease (CHD is a complex human disease associated with inflammation and oxidative stress. The underlying mechanisms and diagnostic biomarkers for the different types of CHD remain poorly defined. Metabolomics has been increasingly recognized as an enabling technique with the potential to identify key metabolomic features in an attempt to understand the pathophysiology and differentiate different stages of CHD. We performed comprehensive metabolomic analysis in human plasma from 28 human subjects with stable angina (SA, myocardial infarction (MI, and healthy control (HC. Subsequent analysis demonstrated a uniquely altered metabolic profile in these CHD: a total of 18, 37 and 36 differential metabolites were identified to distinguish SA from HC, MI from SA, and MI from HC groups respectively. Among these metabolites, glycerophospholipid (GPL metabolism emerged as the most significantly disturbed pathway. Next, we used a targeted metabolomic approach to systematically analyze GPL, oxidized phospholipid (oxPL, and downstream metabolites derived from polyunsaturated fatty acids (PUFAs, such as arachidonic acid and linoleic acid. Surprisingly, lipids associated with lipid peroxidation (LPO pathways including oxidized PL and isoprostanes, isomers of prostaglandins, were significantly elevated in plasma of MI patients comparing to HC and SA, consistent with the notion that oxidative stress-induced LPO is a prominent feature in CHD. Our studies using the state-of-the-art metabolomics help to understand the underlying biological mechanisms involved in the pathogenesis of CHD; LPO metabolites may serve as potential biomarkers to differentiation MI from SA and HC. Keywords: Metabolomics, Lipid peroxidation, Lipidomics, Myocardial infarction, Isoprostanes, Coronary heart disease (CHD

  8. Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate.

    Science.gov (United States)

    Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O'Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

    2014-06-01

    Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (P=0.001). APD decreased during the stressful parts of the film clip, for example, for global right ventricular activation recovery interval at end of film clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end film left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the film clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate. © 2014 American Heart Association, Inc.

  9. Human Fitting Studies of Cleveland Clinic Continuous-Flow Total Artificial Heart

    Science.gov (United States)

    Karimov, Jamshid H.; Steffen, Robert J.; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Cruz, Vincent; Golding, Leonard A.R.; Fukamachi, Kiyotaka; Moazami, Nader

    2015-01-01

    Implantation of mechanical circulatory support devices is challenging, especially in patients with a small chest cavity. We evaluated how well the Cleveland Clinic continuous-flow total artificial heart (CFTAH) fit the anatomy of patients about to receive a heart transplant. A mock pump model of the CFTAH was rapid-prototyped using biocompatible materials. The model was brought to the operative table, and the direction, length, and angulation of the inflow/outflow ports and outflow conduits were evaluated after the recipient's ventricles had been resected. Thoracic cavity measurements were based on preoperative computed tomographic data. The CFTAH fit well in all five patients (height, 170 ± 9 cm; weight, 75 ± 24 kg). Body surface area was 1.9 ± 0.3 m2 (range, 1.6-2.1 m2). The required inflow and outflow port orientation of both the left and right housings appeared consistent with the current version of the CFTAH implanted in calves. The left outflow conduit remained straight, but the right outflow direction necessitated a 73 ± 22 degree angulation to prevent potential kinking when crossing over the connected left outflow. These data support the fact that our design achieves the proper anatomical relationship of the CFTAH to a patient's native vessels. PMID:25806613

  10. Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity

    Directory of Open Access Journals (Sweden)

    Ashraf H. ElGhandour

    2009-04-01

    Full Text Available Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin’s lymphoma (NHL may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP, not exceeding the total allowed dose of doxorubicin (500 mg/m2. Ten healthy controls were included in our study. Human heart-type fatty acid binding protein (H-FABP was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.

  11. Acute cardiovascular toxicity of sterilizers, PHMG, and PGH: severe inflammation in human cells and heart failure in zebrafish.

    Science.gov (United States)

    Kim, Jae-Yong; Kim, Hak Hyeon; Cho, Kyung-Hyun

    2013-06-01

    In 2011, dozens of children and pregnant women in Korea died by exposure to sterilizer for household humidifier, such as Oxy(®) and Cefu(®). Until now, however, it remains unknown how the sterilizer affect the human health to cause the acute deaths. To find its toxicity for organ, we investigated the putative toxicity of the sterilizer in the cardiovascular system. The sterilizers, polyhexamethylene guanidine phosphate (PHMG, Cefu(®)), and oligo-[2-(2-ethoxy)-ethoxyethyl)-guanidinium-chloride (PGH, Oxy(®)) were treated to human lipoproteins, macrophages, and dermal fibroblast cells. The PGH and PHMG at normal dosages caused severe atherogenic process in human macrophages, cytotoxic effect, and aging in human dermal cell. Zebrafish embryos, which were exposed to the sterilizer, showed early death with acute inflammation and attenuated developmental speed. All zebrafish exposed to the working concentration of PHMG (final 0.3 %) and PGH (final 10 mM) died within 70 min and displayed acute increases in serum triacylglycerol level and fatty liver induction. The dead zebrafish showed severe accumulation of fibrous collagen in the bulbous artery of the heart with elevation of reactive oxygen species. In conclusion, the sterilizers showed acute toxic effect in blood circulation system, causing by severe inflammation, atherogenesis, and aging, with embryo toxicity.

  12. The Development of Marine Accidents Human Reliability Assessment Approach: HEART Methodology and MOP Model

    OpenAIRE

    Ludfi Pratiwi Bowo; Wanginingastuti Mutmainnah; Masao Furusho

    2017-01-01

    Humans are one of the important factors in the assessment of accidents, particularly marine accidents. Hence, studies are conducted to assess the contribution of human factors in accidents. There are two generations of Human Reliability Assessment (HRA) that have been developed. Those methodologies are classified by the differences of viewpoints of problem-solving, as the first generation and second generation. The accident analysis can be determined using three techniques of analysis; sequen...

  13. Enhanced Chromatographic Determination of Nicotine in Human Plasma: Applied to Human Volunteers.

    Science.gov (United States)

    Ayoub, Bassam M; Mohamady, Samy; Hendy, Moataz S; Elmazar, Mohamed M

    2015-12-01

    Development of enhanced UPLC-UV method for determination of nicotine in human plasma was achieved on a Symmetry(®) C18 column (100 mm × 2.1 mm, 2.2 μm) applying isocratic elution based on Methanol: Acetonitrile: Phosphate Buffer (pH: 2.7) with the ratio (20:30:50, v/v/v) as a mobile phase. The ultraviolet detector was operated at 260 nm. The mobile phase was pumped through the column at a flow rate of 0.2 mL min(-1). The column temperature was adjusted to 50ºC and the injection volume was 2 μL. Quinine was selected as an internal standard (IS) due to its structure similarity to nicotine having basic pyridine ring to optimize the liquid liquid extraction procedure using diethyl ether coupled with vacuum evaporation at 40°C. Validation parameters for nicotine were found to be acceptable over the concentration range of 2.5-50 ng ml(-1). The application of the proposed method on four healthy human volunteers was approved by the ethical committee. The study was carried out under fasting conditions and the concerned subjects were informed about the objectives and possible risks involved in the study. The proposed method proved to be simple and fast which is a major advantage to analyze large number of samples per day using the accelerated vacuum evaporation technique. The method showed satisfactory data for all the parameters tested within the limits for bioanalytical assays. The lower limit of quantification (LLOQ) permits the application of the method for further pharmacological and clinical studies.

  14. The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses α Myosin Heavy-Chain Gene Expression

    Science.gov (United States)

    Sucharov, Carmen C.; Helmke, Steve M.; Langer, Stephen J.; Perryman, M. Benjamin; Bristow, Michael; Leinwand, Leslie

    2004-01-01

    Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure. PMID:15367688

  15. Enhanced/Synthetic Vision Systems - Human factors research and implications for future systems

    Science.gov (United States)

    Foyle, David C.; Ahumada, Albert J.; Larimer, James; Sweet, Barbara T.

    1992-01-01

    This paper reviews recent human factors research studies conducted in the Aerospace Human Factors Research Division at NASA Ames Research Center related to the development and usage of Enhanced or Synthetic Vision Systems. Research discussed includes studies of field of view (FOV), representational differences of infrared (IR) imagery, head-up display (HUD) symbology, HUD advanced concept designs, sensor fusion, and sensor/database fusion and evaluation. Implications for the design and usage of Enhanced or Synthetic Vision Systems are discussed.

  16. Engineering Education Development to Enhance Human Skill in DENSO

    Science.gov (United States)

    Isogai, Emiko; Nuka, Takeji

    Importance of human skills such as communication or instruction capability to their staff members has recently been highlighted in a workplace, due to decreasing opportunity of face-to-face communication between supervisors and their staff, or Instruction capability through OJT (On the Job Training) . Currently, communication skills are being reinforced mainly through OJT at DENSO. Therefore, as part of supplemental support tools, DENSO has established comprehensive engineers training program on off-JT basis for developing human skills, covering from newly employeed enginners up to managerial class since 2003. This paper describes education activities and reports the results.

  17. A study on human performance enhancement plan in maintenance field by survey on actual condition of human performance tools - 15035

    International Nuclear Information System (INIS)

    Park, J.; Jeong, H.; Kim, Y.

    2015-01-01

    Human errors in nuclear power plant are one of the important factors that may cause reactor trip. Most operating companies of nuclear power plants manage human factor systematically through tools like HPES (Human Performance Enhancement), PSR (Periodic Safety Review), OE (Operating Experience), human performance tools, safety culture assessment and CAP (Corrective Action Program). But human factors are managed passively in maintenance field, because maintenance works are carrying out by partner companies. KHNP also contracts the maintenance work to the partner companies, and advise them to use human performance tools. But the actual condition on partner companies has not been surveyed. This paper suggests some plans that can improve human performance by analyzing the opinion of partner company employees about the causes and solutions of human errors, by analyzing utilization of human performance tools and by comparing the results of the partner companies survey with the results of the operating company survey. The survey is conducted to 3 partner companies by similar contents and categories in order to compare partner company with operating company, and the main analysis fields are the following: -1) Level of understanding and utilization of the human performance tools, -2) Difficulties of applying the human performance tools, -3) Level of employee's training (or education) in the use of the human performance tools, and -4) Root causes of human errors and countermeasures. (authors)

  18. The Effect of Multispectral Image Fusion Enhancement on Human Efficiency

    Science.gov (United States)

    2017-03-20

    and discrete wavelet transformation (DWT). A seventh function was added after we noticed a number of cases where PCA produced uninterpretable...component analysis and adjusted PCA Principal component analysis (PCA) is a general math - ematical technique that transforms a set of potentially correlated...equivalent to sampling the image with Laplacian operators of many scales, which tends to enhance salient image features. Discrete wavelet transform The

  19. Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Dehai Yu

    2017-01-01

    Full Text Available Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal. By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.

  20. Development of the Human Placenta and Fetal Heart: Synergic or Independent?

    Directory of Open Access Journals (Sweden)

    Graham J. Burton

    2018-04-01

    Full Text Available The placenta is the largest fetal organ, and toward the end of pregnancy the umbilical circulation receives at least 40% of the biventricular cardiac output. It is not surprising, therefore, that there are likely to be close haemodynamic links between the development of the placenta and the fetal heart. Development of the placenta is precocious, and in advance of that of the fetus. The placenta undergoes considerable remodeling at the end of the first trimester of pregnancy, and its vasculature is capable of adapting to environmental conditions and to variations in the blood supply received from the mother. There are two components to the placental membranes to consider, the secondary yolk sac and the chorioallantoic placenta. The yolk sac is the first of the extraembryonic membranes to be vascularized, and condensations in the mesenchyme at ~17 days post-conception (p.c. give rise to endothelial and erythroid precursors. A network of blood vessels is established ~24 days p.c., with the vitelline vein draining through the region of the developing liver into the sinus venosus. Gestational sacs of early pregnancy failures often display aberrant development of the yolk sac, which is likely to be secondary to abnormal fetal development. Vasculogenesis occurs in the villous mesenchyme of the chorioallantoic placenta at a similarly early stage. Nucleated erythrocytes occupy the lumens of the placental capillaries and end-diastolic flow is absent in the umbilical arterial circulation throughout most of the first trimester, indicating a high resistance to blood flow. Resistance begins to fall in the umbilico-placental circulation around 12–14 weeks. During normal early pregnancy the placental capillary network is plastic, and considerable remodeling occurs in response to the local oxygen concentration, and in particular to oxidative stress. In pregnancies complicated by preeclampsia and/or fetal growth restriction, utero-placental malperfusion induces

  1. Enlarged Heart

    Science.gov (United States)

    ... rheumatic fever, a heart defect, infections (infectious endocarditis), connective tissue disorders, certain medications or radiation treatments for cancer, your heart may enlarge. Disease of the heart ...

  2. Enhancement, ethics and society: towards an empirical research agenda for the medical humanities and social sciences.

    Science.gov (United States)

    Pickersgill, Martyn; Hogle, Linda

    2015-12-01

    For some time now, bioethicists have paid close attention to issues associated with 'enhancement'; specifically, the appropriate use and regulation of substances and artefacts understood by some to improve the functioning of human bodies beyond that associated with 'normal' function. Medical humanities scholars (aside from philosophers and lawyers) and social scientists have not been frequent participants in debates around enhancement, but could shine a bright light on the range of dilemmas and opportunities techniques of enhancement are purported to introduce. In this paper, we argue that empirical research into the notion and practice of enhancement is necessary and timely. Such work could fruitfully engage with-and further develop-existing conceptual repertoires within the medical humanities and social sciences in ways that would afford benefit to scholars in those disciplines. We maintain that empirical engagements could also provide important resources to bioethicists seeking to regulate new enhancements in ways that are sensitive to societal context and cultural difference. To this end, we outline an empirical agenda for the medical humanities and social sciences around enhancement, emphasising especially how science and technology studies could bring benefits to-and be benefitted by-research in this area. We also use the example of (pharmaceutical) cognitive enhancement to show how empirical studies of actual and likely enhancement practices can nuance resonant bioethical debates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Functional assessment of human enhancer activities using whole-genome STARR-sequencing.

    Science.gov (United States)

    Liu, Yuwen; Yu, Shan; Dhiman, Vineet K; Brunetti, Tonya; Eckart, Heather; White, Kevin P

    2017-11-20

    Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome.  In the current study, we use a human prostate cancer cell line, LNCaP as a model to perform whole human genome STARR-seq (WHG-STARR-seq) to reliably obtain an assessment of enhancer activity. This approach builds upon previously developed STARR-seq in the fly genome and CapSTARR-seq techniques in targeted human genomic regions. With an improved library preparation strategy, our approach greatly increases the library complexity per unit of starting material, which makes it feasible and cost-effective to explore the landscape of regulatory activity in the much larger human genome. In addition to our ability to identify active, accessible enhancers located in open chromatin regions, we can also detect sequences with the potential for enhancer activity that are located in inaccessible, closed chromatin regions. When treated with the histone deacetylase inhibitor, Trichostatin A, genes nearby this latter class of enhancers are up-regulated, demonstrating the potential for endogenous functionality of these regulatory elements. WHG-STARR-seq provides an improved approach to current pipelines for analysis of high complexity genomes to gain a better understanding of the intricacies of transcriptional regulation.

  4. The Effect of Multispectral Image Fusion Enhancement on Human Efficiency

    Science.gov (United States)

    2017-03-20

    basic human behavior. The former asks participants for rankings of characteristics ranging from pure preference of imagery up to self-ratings of their...PCA) is a general math - ematical technique that transforms a set of potentially correlated variables into a set of linearly uncorrelated vari- ables

  5. Enhancement of Human Cheek Skin Texture by Acacia Nilotica Bark ...

    African Journals Online (AJOL)

    HP

    Purpose: To evaluate the effect of a topical application of a cream formulation containing extract of. Acacia nilotica bark extract on human cheek skin texture. Methods: A cream containing 3 % concentrated extract of Acacia nilotica bark was developed by entrapping the extract in the internal aqueous phase of the cream ...

  6. Erythropoietin treatment enhances muscle mitochondrial capacity in humans

    DEFF Research Database (Denmark)

    Plenge, Ulla; Belhage, Bo; Guadalupe-Grau, Amelia

    2012-01-01

    in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis...

  7. Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies.

    Science.gov (United States)

    Heiskanen, Nonna; Saarelainen, Heli; Valtonen, Pirjo; Lyyra-Laitinen, Tiina; Laitinen, Tomi; Vanninen, Esko; Heinonen, Seppo

    2008-11-01

    The aim of the present study was to evaluate pregnancy-related changes in autonomic regulatory functions in healthy subjects. We studied cardiovascular autonomic responses to head-up tilt (HUT) in 28 pregnant women during the third trimester of pregnancy and 3 months after parturition. The maternal ECG and non-invasive beat-to-beat blood pressure were recorded in the horizontal position (left-lateral position) and during HUT in the upright position. Stroke volume was assessed from blood pressure signal by using the arterial pulse contour method. Heart rate variability (HRV) was analysed in frequency domain, and baroreflex sensitivity by the cross-spectral and the sequence methods. In the horizontal position, all frequency components of HRV were lower during pregnancy than 3 months after parturition (P pregnancy had no influence on normalized low frequency and high frequency powers. During pregnancy haemodynamics was well balanced with only minor changes in response to postural change while haemodynamic responses to HUT were more remarkable after parturition. In pregnant women HRV and especially its very low frequency component increased in response to HUT, whereas at 3 months after parturition the direction of these changes was opposite. Parasympathetic deactivation towards term is likely to contribute to increased heart rate and cardiac output at rest, whereas restored sympathetic modulation with modest responses may contribute stable peripheral resistance and sufficient placental blood supply under stimulated conditions. It is important to understand cardiovascular autonomic nervous system and haemodynamic control in normal pregnancy before being able to judge whether they are dysregulated in complicated pregnancies.

  8. An integrative analysis of DNA methylation and RNA-Seq data for human heart, kidney and liver

    Directory of Open Access Journals (Sweden)

    Xie Linglin

    2011-12-01

    Full Text Available Abstract Background Many groups, including our own, have proposed the use of DNA methylation profiles as biomarkers for various disease states. While much research has been done identifying DNA methylation signatures in cancer vs. normal etc., we still lack sufficient knowledge of the role that differential methylation plays during normal cellular differentiation and tissue specification. We also need thorough, genome level studies to determine the meaning of methylation of individual CpG dinucleotides in terms of gene expression. Results In this study, we have used (insert statistical method here to compile unique DNA methylation signatures from normal human heart, lung, and kidney using the Illumina Infinium 27 K methylation arraysand compared those to gene expression by RNA sequencing. We have identified unique signatures of global DNA methylation for human heart, kidney and liver, and showed that DNA methylation data can be used to correctly classify various tissues. It indicates that DNA methylation reflects tissue specificity and may play an important role in tissue differentiation. The integrative analysis of methylation and RNA-Seq data showed that gene methylation and its transcriptional levels were comprehensively correlated. The location of methylation markers in terms of distance to transcription start site and CpG island showed no effects on the regulation of gene expression by DNA methylation in normal tissues. Conclusions This study showed that an integrative analysis of methylation array and RNA-Seq data can be utilized to discover the global regulation of gene expression by DNA methylation and suggests that DNA methylation plays an important role in normal tissue differentiation via modulation of gene expression.

  9. The role of human reliability analysis for enhancing crew performance

    International Nuclear Information System (INIS)

    Hannaman, G.W.; Joksimovich, V.; Worledge, D.H.; Spurgin, A.J.

    1986-01-01

    This paper summarizes some aspects of EPRI-sponsored research undertaken in support of improving the PRA technology. In particular, the consideration of how human actions that impact accident sequences can be analyzed in a systematic way to supplement the type of ergonomic studies normally carried out in support of control room design. The HRA/PRA approach described not only identifies the operator information and interface needs, but also helps to identify issues and areas for additional research. The process includes a link to data collections. Preliminary collections of data and analytical benchmark support the idea that such analytical frameworks and models provide support for ranking the importance of various human reliability issues

  10. Virtual assistant: Enhancing content acquisition by eliciting information from humans

    OpenAIRE

    Ozeki, Motoyuki; Maeda, Shunichi; Obata, Kanako; Nakamura, Yuichi

    2009-01-01

    In this paper, we propose the "Virtual Assistant, " a novel framework for supporting knowledge capturing in videos. The Virtual Assistant is an artificial agent that simulates a human assistant shown in TV programs and prompts users to provide feedback by asking questions. This framework ensures that sufficient information is provided in the captured content while users interact in a natural and enjoyable way with the agent. We developed a prototype agent based on a chatbot-like approach and ...

  11. Erythropoietin enhances hippocampal response during memory retrieval in humans

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla; O'Sullivan, Ursula; Harmer, Catherine J

    2007-01-01

    Although erythropoietin (Epo) is best known for its effects on erythropoiesis, recent evidence suggests that it also has neurotrophic and neuroprotective properties in animal models of hippocampal function. Such an action in humans would make it an intriguing novel compound for the treatment....... This is consistent with upregulation of hippocampal BDNF and neurotrophic actions found in animals and highlights Epo as a promising candidate for treatment of psychiatric disorders....

  12. A new dynamic 3D virtual methodology for teaching the mechanics of atrial septation as seen in the human heart.

    Science.gov (United States)

    Schleich, Jean-Marc; Dillenseger, Jean-Louis; Houyel, Lucile; Almange, Claude; Anderson, Robert H

    2009-01-01

    Learning embryology remains difficult, since it requires understanding of many complex phenomena. The temporal evolution of developmental events has classically been illustrated using cartoons, which create difficulty in linking spatial and temporal aspects, such correlation being the keystone of descriptive embryology. We synthesized the bibliographic data from recent studies of atrial septal development. On the basis of this synthesis, consensus on the stages of atrial septation as seen in the human heart has been reached by a group of experts in cardiac embryology and pediatric cardiology. This has permitted the preparation of three-dimensional (3D) computer graphic objects for the anatomical components involved in the different stages of normal human atrial septation. We have provided a virtual guide to the process of normal atrial septation, the animation providing an appreciation of the temporal and morphologic events necessary to separate the systemic and pulmonary venous returns. We have shown that our animations of normal human atrial septation increase significantly the teaching of the complex developmental processes involved, and provide a new dynamic for the process of learning.

  13. 76 FR 54408 - Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing...

    Science.gov (United States)

    2011-09-01

    ... and Drug Administration 21 CFR Parts 50 and 56 Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators; Extension of... Secretary of the Department of Health and Human Services (HHS) in coordination with the Office of Science...

  14. Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progenitors.

    Science.gov (United States)

    El Harane, Nadia; Kervadec, Anaïs; Bellamy, Valérie; Pidial, Laetitia; Neametalla, Hany J; Perier, Marie-Cécile; Lima Correa, Bruna; Thiébault, Léa; Cagnard, Nicolas; Duché, Angéline; Brunaud, Camille; Lemitre, Mathilde; Gauthier, Jeanne; Bourdillon, Alexandra T; Renault, Marc P; Hovhannisyan, Yeranuhi; Paiva, Solenne; Colas, Alexandre R; Agbulut, Onnik; Hagège, Albert; Silvestre, Jean-Sébastien; Menasché, Philippe; Renault, Nisa K E

    2018-05-21

    We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy. In vitro bioactivity assays were used to evaluate their cellular effects. Cell and EV microRNA (miRNA) content were assessed by miRNA array. Myocardial infarction was induced in 199 nude mice. Three weeks later, mice with left ventricular ejection fraction (LVEF) ≤ 45% received transcutaneous echo-guided injections of iPSC-CM (1.4 × 106, n = 19), iPSC-Pg (1.4 × 106, n = 17), total EV secreted by 1.4 × 106 iPSC-Pg (n = 19), or phosphate-buffered saline (control, n = 17) into the peri-infarct myocardium. Seven weeks later, hearts were evaluated by echocardiography, histology, and gene expression profiling, blinded to treatment group. In vitro, EV were internalized by target cells, increased cell survival, cell proliferation, and endothelial cell migration in a dose-dependent manner and stimulated tube formation. Extracellular vesicles were rich in miRNAs and most of the 16 highly abundant, evolutionarily conserved miRNAs are associated with tissue-repair pathways. In vivo, EV outperformed cell injections, significantly improving cardiac function through decreased left ventricular volumes (left ventricular end systolic volume: -11%, P < 0.001; left

  15. Human developmental enhancers conserved between deuterostomes and protostomes.

    Directory of Open Access Journals (Sweden)

    Shoa L Clarke

    Full Text Available The identification of homologies, whether morphological, molecular, or genetic, is fundamental to our understanding of common biological principles. Homologies bridging the great divide between deuterostomes and protostomes have served as the basis for current models of animal evolution and development. It is now appreciated that these two clades share a common developmental toolkit consisting of conserved transcription factors and signaling pathways. These patterning genes sometimes show common expression patterns and genetic interactions, suggesting the existence of similar or even conserved regulatory apparatus. However, previous studies have found no regulatory sequence conserved between deuterostomes and protostomes. Here we describe the first such enhancers, which we call bilaterian conserved regulatory elements (Bicores. Bicores show conservation of sequence and gene synteny. Sequence conservation of Bicores reflects conserved patterns of transcription factor binding sites. We predict that Bicores act as response elements to signaling pathways, and we show that Bicores are developmental enhancers that drive expression of transcriptional repressors in the vertebrate central nervous system. Although the small number of identified Bicores suggests extensive rewiring of cis-regulation between the protostome and deuterostome clades, additional Bicores may be revealed as our understanding of cis-regulatory logic and sample of bilaterian genomes continue to grow.

  16. Effect of global cardiac ischemia on human ventricular fibrillation: insights from a multi-scale mechanistic model of the human heart.

    Directory of Open Access Journals (Sweden)

    Ivan V Kazbanov

    2014-11-01

    Full Text Available Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF, which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements.

  17. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Hu, Huimin; Qiu, Weimin

    2018-01-01

    Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined...... the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte...

  18. Nietzsche and Human Enhancement. On the Concept of Life

    Directory of Open Access Journals (Sweden)

    Marina García-Granero

    2017-11-01

    Full Text Available This paper exposes the dialogue between Nietzsche and the Darwinian school, highlighting the contrast between two different concepts of «life»: the Darwinian struggle for life or life as will to power. In opposition to the natural selection, which according to nietzsche doesn’t favor the strong and powerful but the mediocre and the many, the German philosopher conceives a breeding (Züchtung, a formation that is physiological as well as moral, and aspires to a true elevation of the human being, through the overcoming of nihilism and the transvaluation of all values from a vitalist perspective.

  19. Social interaction enhances motor resonance for observed human actions.

    Science.gov (United States)

    Hogeveen, Jeremy; Obhi, Sukhvinder S

    2012-04-25

    Understanding the neural basis of social behavior has become an important goal for cognitive neuroscience and a key aim is to link neural processes observed in the laboratory to more naturalistic social behaviors in real-world contexts. Although it is accepted that mirror mechanisms contribute to the occurrence of motor resonance (MR) and are common to action execution, observation, and imitation, questions remain about mirror (and MR) involvement in real social behavior and in processing nonhuman actions. To determine whether social interaction primes the MR system, groups of participants engaged or did not engage in a social interaction before observing human or robotic actions. During observation, MR was assessed via motor-evoked potentials elicited with transcranial magnetic stimulation. Compared with participants who did not engage in a prior social interaction, participants who engaged in the social interaction showed a significant increase in MR for human actions. In contrast, social interaction did not increase MR for robot actions. Thus, naturalistic social interaction and laboratory action observation tasks appear to involve common MR mechanisms, and recent experience tunes the system to particular agent types.

  20. Oxytocin modulates human communication by enhancing cognitive exploration.

    Science.gov (United States)

    de Boer, Miriam; Kokal, Idil; Blokpoel, Mark; Liu, Rui; Stolk, Arjen; Roelofs, Karin; van Rooij, Iris; Toni, Ivan

    2017-12-01

    Oxytocin is a neuropeptide known to influence how humans share material resources. Here we explore whether oxytocin influences how we share knowledge. We focus on two distinguishing features of human communication, namely the ability to select communicative signals that disambiguate the many-to-many mappings that exist between a signal's form and meaning, and adjustments of those signals to the presumed cognitive characteristics of the addressee ("audience design"). Fifty-five males participated in a randomized, double-blind, placebo controlled experiment involving the intranasal administration of oxytocin. The participants produced novel non-verbal communicative signals towards two different addressees, an adult or a child, in an experimentally-controlled live interactive setting. We found that oxytocin administration drives participants to generate signals of higher referential quality, i.e. signals that disambiguate more communicative problems; and to rapidly adjust those communicative signals to what the addressee understands. The combined effects of oxytocin on referential quality and audience design fit with the notion that oxytocin administration leads participants to explore more pervasively behaviors that can convey their intention, and diverse models of the addressees. These findings suggest that, besides affecting prosocial drive and salience of social cues, oxytocin influences how we share knowledge by promoting cognitive exploration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart

    NARCIS (Netherlands)

    Schultz, D; Mikala, G; Yatani, A; Engle, D B; Iles, D E; Segers, B; Sinke, R J; Weghuis, D O; Klöckner, U; Wakamori, M

    1993-01-01

    A unique structural variant of the cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha 1 subunits. However, differences from

  2. Effects of halothane on the conduction system of the heart in humans

    NARCIS (Netherlands)

    Scheffer, G. J.; Jonges, R.; Holley, H. S.; Grimbergen, C. A.; Ros, H. H.; Peper, A.; Booij, L. H.

    1989-01-01

    The effects of 2.0 MAC halothane on atrioventricular conduction times in humans were studied. A real-time recording system for the detection of surface His-Purkinje potentials based on signal averaging techniques was used. Recordings were made in 23 patients before and after the administration of

  3. Characterization of Common Measures of Heart Period Variability in Healthy Human Subjects: Implications for Patient Monitoring

    Science.gov (United States)

    2010-01-01

    sports medicine and science. Sports Med 2000; 30: 1–15. 41. Eckberg DL. The human respiratory gate. J Physiol 2003; 548: 339–352. 42. Kamen PW, Krum H...in short-term HRV analysis. Biomed Tech 2006; 51: 190–193. 45. Hayano J, Taylor JA, Yamada A, et al. Continuous assessment of hemodynamic control by

  4. Letting Our Hearts Break: On Facing the "Hidden Wound" of Human Supremacy

    Science.gov (United States)

    Martusewicz, Rebecca

    2014-01-01

    In this paper I argue that education must be defined by our willingness to experience compassion in the face of others' suffering and thus by an ethical imperative, and seek to expose psycho-social processes of shame as dark matters that inferiorize and subjugate those expressing such compassion for the more-than-human world. Beginning with…

  5. Heart rate biofeedback fails to enhance children's ability to identify time spent in moderate to vigorous physical activity.

    Science.gov (United States)

    Conley, Marguerite M; Gastin, Paul B; Brown, Helen; Shaw, Christine

    2011-03-01

    Physical activity recommendations for children in several countries advise that all young people should accumulate at least 60 min of moderate to vigorous physical activity every day. Perceiving physical activity intensity, however, can be a difficult task for children and it is not clear whether children can identify their levels of moderate to vigorous physical activity in accordance with the recommended guidelines. This study aimed to (1) explore whether children can identify time spent in moderate to vigorous physical activity; and (2) investigate whether heart rate biofeedback would improve children's ability to estimate time spent in moderate to vigorous physical activity. Thirty seven children (15 boys and 22 girls, mean age 12.6 years) wore data recording Polar E600 heart rate monitors during eight physical education lessons. At the end of each lesson children's estimated time in zone was compared to their actual time in zone. During a six lesson Intervention phase, one class was assigned to a biofeedback group whilst the other class acted as the control group and received no heart rate biofeedback. Post-Intervention, students in the biofeedback group were no better than the control group at estimating time spent in zone (mean relative error of estimation biofeedback group: Pre-Intervention 41±32% to Post-Intervention 28±26%; control group: Pre-Intervention 40±39% to Post-Intervention 31±37%). Thus it seems that identifying time spent in moderate to vigorous physical activity remains a complex task for children aged 11-13 even with the help of heart rate biofeedback. Copyright © 2010 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  6. Radial Pressure Pulse and Heart Rate Variability in Heat- and Cold-Stressed Humans

    Directory of Open Access Journals (Sweden)

    Chin-Ming Huang

    2011-01-01

    Full Text Available This study aims to explore the effects of heat and cold stress on the radial pressure pulse (RPP and heart rate variability (HRV. The subjects immersed their left hand into 45°C and 7°C water for 2 minutes. Sixty healthy subjects (age 25±4 yr; 29 men and 31 women were enrolled in this study. All subjects underwent the supine temperature measurements of the bilateral forearms, brachial arterial blood pressure, HRV and RPP with a pulse analyzer in normothermic conditions, and thermal stresses. The power spectral low-frequency (LF and high-frequency (HF components of HRV decreased in the heat test and increased in the cold test. The heat stress significantly reduced radial augmentation index (AIr (P<.05, but the cold stress significantly increased AIr (P<.01. The spectral energy of RPP did not show any statistical difference in 0∼10 Hz region under both conditions, but in the region of 10∼50 Hz, there was a significant increase (P<.01 in the heat test and a significant decrease in the cold test (P<.01. The changes in AIr induced by heat and cold stress were significantly negatively correlated with the spectral energy in the region of 10∼50 Hz (SE10−50 Hz but not in the region of 0∼10 Hz (SE0−10 Hz. The results demonstrated that the SE10−50 Hz, which only possessed a small percentage in total pulse energy, presented more physiological characteristics than the SE0−10 Hz under the thermal stresses.

  7. Radial Pressure Pulse and Heart Rate Variability in Heat- and Cold-Stressed Humans

    Science.gov (United States)

    Huang, Chin-Ming; Chang, Hsien-Cheh; Kao, Shung-Te; Li, Tsai-Chung; Wei, Ching-Chuan; Chen, Chiachung; Liao, Yin-Tzu; Chen, Fun-Jou

    2011-01-01

    This study aims to explore the effects of heat and cold stress on the radial pressure pulse (RPP) and heart rate variability (HRV). The subjects immersed their left hand into 45°C and 7°C water for 2 minutes. Sixty healthy subjects (age 25 ± 4 yr; 29 men and 31 women) were enrolled in this study. All subjects underwent the supine temperature measurements of the bilateral forearms, brachial arterial blood pressure, HRV and RPP with a pulse analyzer in normothermic conditions, and thermal stresses. The power spectral low-frequency (LF) and high-frequency (HF) components of HRV decreased in the heat test and increased in the cold test. The heat stress significantly reduced radial augmentation index (AIr) (P < .05), but the cold stress significantly increased AIr (P < .01). The spectral energy of RPP did not show any statistical difference in 0 ~ 10 Hz region under both conditions, but in the region of 10 ~ 50 Hz, there was a significant increase (P < .01) in the heat test and a significant decrease in the cold test (P < .01). The changes in AIr induced by heat and cold stress were significantly negatively correlated with the spectral energy in the region of 10 ~ 50 Hz (SE10−50 Hz) but not in the region of 0 ~ 10 Hz (SE0−10 Hz). The results demonstrated that the SE10−50 Hz, which only possessed a small percentage in total pulse energy, presented more physiological characteristics than the SE0−10 Hz under the thermal stresses. PMID:21113292

  8. Efficient computation of electrograms and ECGs in human whole heart simulations using a reaction-eikonal model.

    Science.gov (United States)

    Neic, Aurel; Campos, Fernando O; Prassl, Anton J; Niederer, Steven A; Bishop, Martin J; Vigmond, Edward J; Plank, Gernot

    2017-10-01

    Anatomically accurate and biophysically detailed bidomain models of the human heart have proven a powerful tool for gaining quantitative insight into the links between electrical sources in the myocardium and the concomitant current flow in the surrounding medium as they represent their relationship mechanistically based on first principles. Such models are increasingly considered as a clinical research tool with the perspective of being used, ultimately, as a complementary diagnostic modality. An important prerequisite in many clinical modeling applications is the ability of models to faithfully replicate potential maps and electrograms recorded from a given patient. However, while the personalization of electrophysiology models based on the gold standard bidomain formulation is in principle feasible, the associated computational expenses are significant, rendering their use incompatible with clinical time frames. In this study we report on the development of a novel computationally efficient reaction-eikonal (R-E) model for modeling extracellular potential maps and electrograms. Using a biventricular human electrophysiology model, which incorporates a topologically realistic His-Purkinje system (HPS), we demonstrate by comparing against a high-resolution reaction-diffusion (R-D) bidomain model that the R-E model predicts extracellular potential fields, electrograms as well as ECGs at the body surface with high fidelity and offers vast computational savings greater than three orders of magnitude. Due to their efficiency R-E models are ideally suitable for forward simulations in clinical modeling studies which attempt to personalize electrophysiological model features.

  9. Contrast-enhanced time-resolved 4D MRA of congenital heart and vessel anomalies: image quality and diagnostic value compared with 3D MRA

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, Florian M.; Hunold, Peter; Barkhausen, Joerg [University Hospital Schleswig-Holstein, Clinic for Radiology and Nuclear Medicine, Luebeck (Germany); Theysohn, Jens M.; Kinner, Sonja [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Michna, Dariusz [Elisabeth Hospital, Department of Neonatology, Essen (Germany); Neudorf, Ulrich [University Hospital Essen, Clinic for Pediatrics III, Essen (Germany); Quick, Harald H. [University of Erlangen-Nuernberg, Institute of Medical Physics, Erlangen (Germany)

    2013-09-15

    To evaluate time-resolved interleaved stochastic trajectories (TWIST) contrast-enhanced 4D magnetic resonance angiography (MRA) and compare it with 3D FLASH MRA in patients with congenital heart and vessel anomalies. Twenty-six patients with congenital heart and vessel anomalies underwent contrast-enhanced MRA with both 3D FLASH and 4D TWIST MRA. Images were subjectively evaluated regarding total image quality, artefacts, diagnostic value and added diagnostic value of 4D dynamic imaging. Quantitative comparison included signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and vessel sharpness measurements. Three-dimensional FLASH MRA was judged to be significantly better in terms of image quality (4.0 {+-} 0.6 vs 3.4 {+-} 0.6, P < 0.05) and artefacts (3.8 {+-} 0.4 vs 3.3 {+-} 0.5, P < 0.05); no difference in diagnostic value was found (4.2 {+-} 0.4 vs 4.0 {+-} 0.4); important additional functional information was found in 21/26 patients. SNR and CNR were higher in the pulmonary trunk in 4D TWIST, but slightly higher in the systemic arteries in 3D FLASH. No difference in vessel sharpness delineation was found. Although image quality was inferior compared with 3D FLASH MRA, 4D TWIST MRA yields robust images and added diagnostic value through dynamic acquisition was found. Thus, 4D TWIST MRA is an attractive alternative to 3D FLASH MRA. (orig.)

  10. Significance of myoglobin as an oxygen store and oxygen transporter in the intermittently perfused human heart: a model study.

    Science.gov (United States)

    Endeward, Volker; Gros, Gerolf; Jürgens, Klaus D

    2010-07-01

    The mechanisms by which the left ventricular wall escapes anoxia during the systolic phase of low blood perfusion are investigated, especially the role of myoglobin (Mb), which can (i) store oxygen and (ii) facilitate intracellular oxygen transport. The quantitative role of these two Mb functions is studied in the maximally working human heart. Because discrimination between Mb functions has not been achieved experimentally, we use a Krogh cylinder model here. At a heart rate of 200 beats/min and a 1:1 ratio of diastole/systole, the systole lasts for 150 ms. The basic model assumption is that, with mobile Mb, the oxygen stored in the end-diastolic left ventricle wall exactly meets the demand during the 150 ms of systolic cessation of blood flow. The coronary blood flow necessary to achieve this agrees with literature data. By considering Mb immobile or setting its concentration to zero, respectively, we find that, depending on Mb concentration, Mb-facilitated O(2) transport maintains O(2) supply to the left ventricle wall during 22-34 of the 150 ms, while Mb storage function accounts for a further 12-17 ms. When Mb is completely absent, anoxia begins to develop after 116-99 ms. While Mb plays no significant role during diastole, it supplies O(2) to the left ventricular wall for < or = 50 ms of the 150 ms systole, whereas capillary haemoglobin is responsible for approximately 80 ms. Slight increases in haemoglobin concentration, blood flow, or capillary density can compensate the absence of Mb, a finding which agrees well with the observations using Mb knockout mice.

  11. Chill-inducing music enhances altruism in humans

    Directory of Open Access Journals (Sweden)

    Hajime eFukui

    2014-10-01

    Full Text Available Music is a universal feature of human cultures, and it has both fascinated and troubled many researchers. In this paper we show through the Dictator Game that an individual’s listening to preferred chill-inducing music may promote altruistic behavior that extends beyond the bounds of kin selection or reciprocal altruism. Participants were 22 undergraduate and postgraduate students who were divided into two groups, the In-group (IG and the Out-group (OG, and they acted as dictators. The dictators listened to their own preferred chill-inducing music, to music they disliked, or to silence, and then played the Dictator Game. In this hypothetical experiment, the dictators were given real money (which they did not keep and were asked to distribute it to the recipients, who were presented as stylized images of men and women displayed on a computer screen. The dictators played the Dictator Game both before and after listening to the music. Both male and female dictators gave more money after listening to their preferred music and less after listening to the music they disliked, whereas silence had no effect on the allocated amounts. The group to which the recipient belonged did not influence these trends. The results suggest that listening to preferred chill-inducing music promotes altruistic behavior.

  12. Chill-inducing music enhances altruism in humans.

    Science.gov (United States)

    Fukui, Hajime; Toyoshima, Kumiko

    2014-01-01

    Music is a universal feature of human cultures, and it has both fascinated and troubled many researchers. In this paper we show through the dictator game (DG) that an individual's listening to preferred "chill-inducing" music may promote altruistic behavior that extends beyond the bounds of kin selection or reciprocal altruism. Participants were 22 undergraduate and postgraduate students who were divided into two groups, the in-group and the out-group, and they acted as dictators. The dictators listened to their own preferred "chill-inducing" music, to music they disliked, or to silence, and then played the DG. In this hypothetical experiment, the dictators were given real money (which they did not keep) and were asked to distribute it to the recipients, who were presented as stylized images of men and women displayed on a computer screen. The dictators played the DG both before and after listening to the music. Both male and female dictators gave more money after listening to their preferred music and less after listening to the music they disliked, whereas silence had no effect on the allocated amounts. The group to which the recipient belonged did not influence these trends. The results suggest that listening to preferred "chill-inducing" music promotes altruistic behavior.

  13. Growth hormone and the heart.

    Science.gov (United States)

    Cittadini, A; Longobardi, S; Fazio, S; Saccà, L

    1999-01-01

    Until a few years ago, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were considered essential only to the control of linear growth, glucose homeostasis, and for the maintenance of skeletal muscle mass. A large body of evidence recently coming from animal and human studies has unequivocally proven that the heart is a target organ for the GH/IGF-1 axis. Specifically GH exerts both direct and indirect cardiovascular actions. Among the direct effects, the ability of GH to trigger cardiac tissue growth plays a pivotal role. Another direct effect is to augment cardiac contractility, independent of myocardial growth. Direct effects of GH also include the improvement of myocardial energetics and mechanical efficiency. Indirect effects of GH on the heart include decreased peripheral vascular resistance (PVR), expansion of blood volume, increased glomerular filtration rate, enhanced respiratory activity, increased skeletal muscle performance, and psychological well-being. Among them, the most consistently found is the decrease of PVR. GH may also raise preload through its sodium-retaining action and its interference with the hormonal system that regulates water and electrolyte metabolism. Particularly important is the effect of GH on skeletal muscle mass and performance. Taking into account that heart failure is characterized by left ventricular dilation, reduced cardiac contractility, and increase of wall stress and peripheral vascular resistance, GH may be beneficial for treatment of heart failure. Animal studies and preliminary human trials have confirmed the validity of the GH approach to the treatment of heart failure. Larger placebo-controlled human studies represent the main focus of future investigations.

  14. Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

    Directory of Open Access Journals (Sweden)

    Knüchel Ruth

    2008-05-01

    Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian

  15. Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors.

    Science.gov (United States)

    Miller, Paul H; Cheung, Alice M S; Beer, Philip A; Knapp, David J H F; Dhillon, Kiran; Rabu, Gabrielle; Rostamirad, Shabnam; Humphries, R Keith; Eaves, Connie J

    2013-01-31

    Better methods to characterize normal human hematopoietic cells with short-term repopulating activity cells (STRCs) are needed to facilitate improving recovery rates in transplanted patients.We now show that 5-fold more human myeloid cells are produced in sublethally irradiated NOD/SCID-IL-2Receptor-γchain-null (NSG) mice engineered to constitutively produce human interleukin-3, granulocyte-macrophage colony-stimulating factor and Steel factor (NSG-3GS mice) than in regular NSG mice 3 weeks after an intravenous injection of CD34 human cord blood cells. Importantly, the NSG-3GS mice also show a concomitant and matched increase in circulating mature human neutrophils. Imaging NSG-3GS recipients of lenti-luciferase-transduced cells showed that human cells being produced 3 weeks posttransplant were heterogeneously distributed, validating the blood as a more representative measure of transplanted STRC activity. Limiting dilution transplants further demonstrated that the early increase in human granulopoiesis in NSG-3GS mice reflects an expanded output of differentiated cells per STRC rather than an increase in STRC detection. NSG-3GS mice support enhanced clonal outputs from human short-term repopulating cells (STRCs) without affecting their engrafting efficiency. Increased human STRC clone sizes enable their more precise and efficient measurement by peripheral blood monitoring.

  16. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun [Division of heavy ion clinical research, Korea University, Seoul (Korea, Republic of); Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2012-11-15

    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy.

  17. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    International Nuclear Information System (INIS)

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun; Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook

    2012-01-01

    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy

  18. Hairpin formation within the enhancer region of the human enkephalin gene

    International Nuclear Information System (INIS)

    McMurray, C.T.; Douglass, J.O.; Wilson, W.D.

    1991-01-01

    The 3',5'-cyclic adenosine monophosphate (cAMP)-inducible enhancer of the human enkephaline gene is located within an imperfect palindrom of 23 base pairs. The authors have found that a 23-base-pair oligonucleotide duplex containing the enhancer undergoes a reversible conformational transition from the duplex to two individual hairpin structures each formed from one strand of the duplex. Each individual hairpin forms with mismatched base pairs, one containing two GT pairs and the other containing two AC pairs. The conformational transition is stabilized by proton transfer to the hairpin containing AC mismatched pairs. The unique physical and thermodynamic properties of the enkephalin enhancer DNA suggest a model in which DNA secondary structure within the enhancer region plays and active role incAMP-inducible activation of the human enkephalin gene via formation of cruciform structures

  19. Hairpin formation within the enhancer region of the human enkephalin gene

    Energy Technology Data Exchange (ETDEWEB)

    McMurray, C.T.; Douglass, J.O. (Oregon Health Sciences Univ., Portland (United States)); Wilson, W.D. (Georgia State Univ., Atlanta (United States))

    1991-01-15

    The 3{prime},5{prime}-cyclic adenosine monophosphate (cAMP)-inducible enhancer of the human enkephaline gene is located within an imperfect palindrom of 23 base pairs. The authors have found that a 23-base-pair oligonucleotide duplex containing the enhancer undergoes a reversible conformational transition from the duplex to two individual hairpin structures each formed from one strand of the duplex. Each individual hairpin forms with mismatched base pairs, one containing two GT pairs and the other containing two AC pairs. The conformational transition is stabilized by proton transfer to the hairpin containing AC mismatched pairs. The unique physical and thermodynamic properties of the enkephalin enhancer DNA suggest a model in which DNA secondary structure within the enhancer region plays and active role incAMP-inducible activation of the human enkephalin gene via formation of cruciform structures.

  20. Enhanced bag of words using multilevel k-means for human activity recognition

    Directory of Open Access Journals (Sweden)

    Motasem Elshourbagy

    2016-07-01

    Full Text Available This paper aims to enhance the bag of features in order to improve the accuracy of human activity recognition. In this paper, human activity recognition process consists of four stages: local space time features detection, feature description, bag of features representation, and SVMs classification. The k-means step in the bag of features is enhanced by applying three levels of clustering: clustering per video, clustering per action class, and clustering for the final code book. The experimental results show that the proposed method of enhancement reduces the time and memory requirements, and enables the use of all training data in the k-means clustering algorithm. The evaluation of accuracy of action classification on two popular datasets (KTH and Weizmann has been performed. In addition, the proposed method improves the human activity recognition accuracy by 5.57% on the KTH dataset using the same detector, descriptor, and classifier.

  1. The Humans in Space Art Program - Engaging the Mind, and the Heart, in Science

    Science.gov (United States)

    McPhee, J. C.

    2017-12-01

    How can we do a better job communicating about space, science and technology, getting more people engaged, understanding the impact that future space exploration will have on their lives, and thinking about how they can contribute? Humans naturally express their visions and interests through various forms of artistic expression because art is inherently capable of expressing not only the "what and how" but also the "why" of ideas. Offering opportunities that integrate space, science and technology with art allows more people to learn about space, relay their visions of the future, and discuss why exploration and research are important. The Humans in Space Art Program, managed by the nonprofit SciArt Exchange, offers a science-integrated-with-art opportunity. Through international online competitions, we invite participants to share their visions of the future using visual, literary, musical and video art. We then use their artwork in multi-media displays and live performances online, locally worldwide, and in space to engage listeners and viewers. The Program has three projects, targeting different types of participants: the Youth Competition (ages 10-18), the Challenge (college and early career) and Celebrity Artist-Fed Engagement (CAFÉ: professional artists). To date, the Program has received 3400 artworks from over 52 countries and displayed the artwork in 110 multi-media events worldwide, on the International Space Station and bounced off the Moon. 100,000's have thus viewed artwork considering topics such as: why we explore; where and how we will go and when; and what we will do when we arrive. The Humans in Space Art Program is a flexible public engagement model applicable to multiple settings, including classrooms, art and entertainment events, and scientific conferences. It provides a system to accessibly inspire all ages about space, science and technology, making them hungry to learn more and to take a personal role.

  2. Characterizing potential heart agents with an isolated perfused heart system

    International Nuclear Information System (INIS)

    Pendleton, D.B.; Sands, H.; Gallagher, B.M.; Camin, L.L.

    1984-01-01

    The authors have used an isolated perfused heart system for characterizing potential myocardial perfusion radiopharamaceuticals. Rabbit or guinea pig (GP) hearts are removed and perfused through the aorta with a blood-free buffer. Heart rate and ventricular pressure are monitored as indices of viability. Tc-99m-MAA is 96-100% retained in these hearts, and Tc-99m human serum albumin shows less than 5% extraction. Tl-201 is 30-40% extracted. It is known that in-vivo, Tc-99m(dmpe)/sub 2/Cl/sub 2//sup +/ is taken up by rabbit heart but not by GP or human heart. Analogous results are obtained with the isolated perfused heart model, where the complex is extracted well by the isolated rabbit heart (24%) but not by the GP heart (<5%). Values are unchanged if human, rabbit or GP blood is mixed and co-injected with the complex. Tc-99m)dmpe)/sub 3//sup +/ is also taken up by rabbit but not by GP hearts in-vivo. However, isolated perfused hearts of both species extract this complex well (45-52%). Heart uptake is diminished to <7% if the complex is pre-equilibrated with human blood. GP blood produces a moderate inhibition (in GP hearts only) and rabbit blood has no effect. This suggests that a human or GP blood factor may have a significant effect on heart uptake of this complex. Tc-99m(CN-t-butyl)/sub 6//sup +/ is taken up well by both rabbit and GP hearts in-vivo, and is extracted 100% by both isolated perfused hearts. Heart retention remains high (73-75%) in the presence of human blood

  3. Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans.

    Science.gov (United States)

    Silvani, Alessandro; Calandra-Buonaura, Giovanna; Johnson, Blair D; van Helmond, Noud; Barletta, Giorgio; Cecere, Anna G; Joyner, Michael J; Cortelli, Pietro

    2017-01-01

    The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological mechanisms that mediate the coupling between HP and SAP in response to different postures, we analyzed the cross-correlation functions between low-frequency HP and SAP fluctuations and estimated cBRS with the sequence technique in healthy male subjects during passive head-up tilt test (HUTT, n = 58), during supine wakefulness, supine slow-wave sleep (SWS), and in the seated and active standing positions ( n = 8), and during progressive loss of 1 L blood ( n = 8) to decrease central venous pressure in the supine position. HUTT, SWS, the seated, and the standing positions, but not blood loss, entailed significant increases in the positive correlation between HP and the previous SAP values, which is the expected result of arterial baroreflex control, compared with baseline recordings in the supine position during wakefulness. These increases were mirrored by increases in the low-frequency variability of SAP in each condition but SWS. cBRS decreased significantly during HUTT, in the seated and standing positions, and after blood loss compared with baseline during wakefulness. These decreases were mirrored by decreases in the RMSSD index, which reflects cardiac vagal modulation. These results support the view that the cBRS decrease associated with the upright posture is a byproduct of decreased cardiac vagal modulation, triggered by the arterial baroreflex in response to central hypovolemia. Conversely, the greater baroreflex contribution to cardiac control associated with upright posture may be explained, at least in part, by enhanced fluctuations of SAP, which elicit a more effective entrainment of HP fluctuations by the arterial baroreflex. These SAP fluctuations may result

  4. Differentiation of hypertensive heart disease with hypertrophy and hepertrophic cardiomyopathy using consecutive time-course images of Gd-DTPA enhanced MRI

    International Nuclear Information System (INIS)

    Ochiai, Kouichi; Isibashi, Yutaka; Shimada, Toshio; Tsukihashi, Hironori; Sato, Hidetoshi; Kitamura, Jun; Morioka, Shigefumi; Kawamitsu, Hideaki; Sugimura, Kazuro

    1996-01-01

    We used consecutive time-course Gd-DTPA contrast magnetic resonance images to differentiate hypertrophic cardiomyopathy (HCM) from hypertensive heart disease with hypertrophy (HHD). Seventeen patients with HCM, 6 patients with HHD and 5 normal subjects (control) were studied. ECG-gated MRI with 1.5T system was performed before and after intravenous injection of Gd-DTPA (0.1mmol/Kg) using spin echo sequence. Gd-DTPA enhanced MRI was repeated every 10 to 55 minutes. We measured signal intensity (SI) of midleft ventricular myocardium and skeletal muscle, and then calculated the ratio between myocardial SI and skeletal muscle SI. Myocardium was enhanced by Gd-DTPA in all patients. However, there was difference in the decay of enhancement effect by Gd-DTPA between HCM and HHD. The decay in HCM was more slowly than in both HHD and control. There was no difference in the decay between HHD and control. The difference in the decay between HCM and HHD became significant 25 minutes after Gd-DTPA injection and lasted until 55 minutes. We conclude that the time-course of the decay of enhancement effect by Gd-DTPA is helpful to differentiate HCM from HHD and the difference of the decay might reflect structural changes of myocardium. (author)

  5. Noninvasive Assessment of Preload Reserve Enhances Risk Stratification of Patients With Heart Failure With Reduced Ejection Fraction.

    Science.gov (United States)

    Matsumoto, Kensuke; Onishi, Akira; Yamada, Hirotsugu; Kusunose, Kenya; Suto, Makiko; Hatani, Yutaka; Matsuzoe, Hiroki; Tatsumi, Kazuhiro; Tanaka, Hidekazu; Hirata, Ken-Ichi

    2018-05-01

    The leg-positive pressure maneuver can safely and noninvasively apply preload stress without increase in total body fluid volume. The purpose of this study was to determine whether preload stress could be useful for risk stratification of patients with heart failure with reduced ejection fraction. For this study, 120 consecutive patients with heart failure with reduced ejection fraction were prospectively recruited. The stroke work index was estimated as product of stroke volume index and mean blood pressure, and the E/e' ratio was calculated to estimate ventricular filling pressure. The echocardiographic parameters were obtained both at rest and during leg-positive pressure stress. During the median follow-up period of 20 months, 30 patients developed adverse cardiovascular events. During preload stress, stroke work index increased significantly (from 3280±1371 to 3857±1581 mm Hg·mL/m 2 ; P <0.001) along with minimal changes in ventricular filling pressure (E/e', from 16±10 to 17±9; P <0.05) in patients without cardiovascular events. However, patients with cardiovascular events showed impairment of Frank-Starling mechanism (stroke work index, from 2863±969 to 2903±1084 mm Hg·mL/m 2 ; P =0.70) and a serious increase in E/e' ratio (from 19±11 to 25±14; P <0.001). Both the patients without contractile reserve and those without diastolic reserve exhibited worse event-free survival than the others ( P <0.001). In a Cox proportional-hazards analysis, the changes in stroke work index (hazard ratio: 0.44 per 500 mm Hg·mL/m 2 increase; P =0.001) and in E/e' (hazard ratio: 2.58 per 5-U increase; P <0.001) were predictors of cardiovascular events. Contractile reserve and diastolic reserve during leg-positive pressure stress are important determinants of cardiovascular outcomes for patients with heart failure with reduced ejection fraction. © 2018 American Heart Association, Inc.

  6. Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts.

    Science.gov (United States)

    Hansen, Brian J; Zhao, Jichao; Csepe, Thomas A; Moore, Brandon T; Li, Ning; Jayne, Laura A; Kalyanasundaram, Anuradha; Lim, Praise; Bratasz, Anna; Powell, Kimerly A; Simonetti, Orlando P; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L; Weiss, Raul; Hummel, John D; Fedorov, Vadim V

    2015-09-14

    The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging. Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7-6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30-100 µM) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles. Published on

  7. Assessment of the effect of left atrial cryoablation enhanced by ganglionated plexi ablation in the treatment of atrial fibrillation in patients undergoing open heart surgery.

    Science.gov (United States)

    Bárta, Jiří; Brát, Radim

    2017-08-17

    The aim of our study was to investigate, whether enhancement of left atrial cryoablation by ablation of the autonomic nervous system of left atrium leads to influencing the outcomes of surgical treatment of atrial fibrillation in patients with structural heart disease undergoing open-heart surgery. The observed patient file consisted of 100 patients, who have undergone a combined open-heart surgery at our department between July 2012 and December 2014. The patients were indicated for the surgical procedure due to structural heart disease, and suffered from paroxysmal, persistent, or long-standing persistent atrial fibrillation. In all cases, left atrial cryoablation was performed in the extent of isolation of pulmonary veins, box lesion, connecting lesion with mitral annulus, amputation of the left atrial appendage and connecting lesion of the appendage base with left pulmonary veins. Furthermore, 35 of the patients underwent mapping and radiofrequency ablation of ganglionated plexi, together with discision and ablation of the ligament of Marshall (Group GP). A control group was consisted of 65 patients without ganglionated plexi intervention (Group LA). The main primary outcome was establishment and duration of sinus rhythm in the course of one-year follow-up. Evaluation of the number of patients with a normal sinus rhythm in per cent has shown comparable values in both groups (Group GP - 93.75%, Group LA - 86.67%, p = 0.485); comparable results were also observed in patients with normal sinus rhythm without anti-arrhythmic treatment in the 12th month (Group GP - 50%, Group LA - 47%, p = 0.306). We have not observed any relation between the recurrence of atrial fibrillation and the presence of a mitral valve surgery, or between the presence of a mitral and tricuspid valves surgery and between the left atrial diameter > 50 mm. Enhancement of left atrial cryoablation by gangionated plexi ablation did not influence the outcomes of surgical ablation due to

  8. Ethical Concerns About Human Genetic Enhancement in the Malay Science Fiction Novels.

    Science.gov (United States)

    Isa, Noor Munirah; Hj Safian Shuri, Muhammad Fakhruddin

    2018-02-01

    Advancements in science and technology have not only brought hope to humankind to produce disease-free offspring, but also offer possibilities to genetically enhance the next generation's traits and capacities. Human genetic enhancement, however, raises complex ethical questions, such as to what extent should it be allowed? It has been a great challenge for humankind to develop robust ethical guidelines for human genetic enhancement that address both public concerns and needs. We believe that research about public concerns is necessary prior to developing such guidelines, yet the issues have not been thoroughly investigated in many countries, including Malaysia. Since the novel often functions as a medium for the public to express their concerns, this paper explores ethical concerns about human genetic enhancement expressed in four Malay science fiction novels namely Klon, Leksikon Ledang, Transgenesis Bisikan Rimba and Transgenik Sifar. Religion has a strong influence on the worldview of the Malays therefore some concerns such as playing God are obviously religious. Association of the negative image of scientists as well as the private research companies with the research on human genetic enhancement reflects the authors' concerns about the main motivations for conducting such research and the extent to which such research will benefit society.

  9. Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity.

    Science.gov (United States)

    Tang, Mingxin; Zhang, Xiaoying; Li, Yingxin; Guan, Yinzheng; Ai, Xiaojie; Szeto, Christopher; Nakayama, Hiroyuki; Zhang, Hongyu; Ge, Shuping; Molkentin, Jeffery D; Houser, Steven R; Chen, Xiongwen

    2010-08-01

    Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavbeta2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon beta-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found: 1) in DTG myocytes, L-type Ca(2+) current (I(Ca,L)) density, myocyte fractional shortening (FS), peak Ca(2+) transients, and sarcoplasmic reticulum (SR) Ca(2+) content (caffeine-induced Ca(2+) transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and 2) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/dt and -dP/dt) measurements were significantly greater in DTG mice than in control mice. However, 1) the cardiac contractility (EF, FS, dP/dt, and -dP/dt)-enhancing effect of the beta-adrenergic agonist isoproterenol (2 microg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of beta-adrenergic stimulation on contraction, Ca(2+) transients, I(Ca,L), and SR Ca(2+) content in DTG myocytes; and 2) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high-activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart.

  10. Heart Failure

    Science.gov (United States)

    Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped ... and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and ...

  11. Human Computer Collaboration at the Edge: Enhancing Collective Situation Understanding with Controlled Natural Language

    Science.gov (United States)

    2016-09-06

    conversational agent with information exchange disabled until the end of the experiment run. The meaning of the indicator in the top- right of the agent... Human Computer Collaboration at the Edge: Enhancing Collective Situation Understanding with Controlled Natural Language Alun Preece∗, William...email: PreeceAD@cardiff.ac.uk †Emerging Technology Services, IBM United Kingdom Ltd, Hursley Park, Winchester, UK ‡US Army Research Laboratory, Human

  12. Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

    Science.gov (United States)

    2016-09-01

    analysis of tumor necrosis factor - alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype...AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor - Associated...Cancer and Impairs Tumor -Associated Angiogenesis 5b. GRANT NUMBER W81XWH-15-1-0296 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  13. Enhanced human somatic cell reprogramming efficiency by fusion of the MYC transactivation domain and OCT4

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2017-12-01

    Full Text Available The development of human induced pluripotent stem cells (iPSCs holds great promise for regenerative medicine. However the iPSC induction efficiency is still very low and with lengthy reprogramming process. We utilized the highly potent transactivation domain (TAD of MYC protein to engineer the human OCT4 fusion proteins. Applying the MYC-TAD-OCT4 fusion proteins in mouse iPSC generation leads to shorter reprogramming dynamics, with earlier activation of pluripotent markers in reprogrammed cells than wild type OCT4 (wt-OCT4. Dramatic enhancement of iPSC colony induction efficiency and shortened reprogramming dynamics were observed when these MYC-TAD-OCT4 fusion proteins were used to reprogram primary human cells. The OCT4 fusion proteins induced human iPSCs are pluripotent. We further show that the MYC Box I (MBI is dispensable while both MBII and the linking region between MBI/II are essential for the enhanced reprogramming activity of MYC-TAD-OCT4 fusion protein. Consistent with an enhanced transcription activity, the engineered OCT4 significantly stimulated the expression of genes specifically targeted by OCT4-alone, OCT4/SOX2, and OCT4/SOX2/KLF4 during human iPSC induction, compared with the wt-OCT4. The MYC-TAD-OCT4 fusion proteins we generated will be valuable tools for studying the reprogramming mechanisms and for efficient iPSC generation for humans as well as for other species.

  14. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    Science.gov (United States)

    Singh, Swati; Kumar, Ashok; Khare, Shashi; Mulchandani, Ashok; Rajesh

    2014-11-01

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml-1 with a limit of detection of 0.16 ng ml-1.

  15. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    International Nuclear Information System (INIS)

    Singh, Swati; Kumar, Ashok; Khare, Shashi; Mulchandani, Ashok; Rajesh

    2014-01-01

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml −1 with a limit of detection of 0.16 ng ml −1

  16. Single-walled carbon nanotubes based chemiresistive genosensor for label-free detection of human rheumatic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Swati; Kumar, Ashok, E-mail: rajesh-csir@yahoo.com, E-mail: ashokigib@rediffmail.com [CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007 (India); Academy of Scientific and Innovative Research (AcSIR), New Delhi (India); Khare, Shashi [National Centre for Disease Control, Sham Nath Marg, Delhi 110054 (India); Mulchandani, Ashok [Department of Chemical and Environmental Engineering, University of California, Riverside, California 92521 (United States); Rajesh, E-mail: rajesh-csir@yahoo.com, E-mail: ashokigib@rediffmail.com [CSIR-National Physical Laboratory, Dr. K. S. Krishnan Road, New Delhi 110012 (India)

    2014-11-24

    A specific and ultrasensitive, label free single-walled carbon nanotubes (SWNTs) based chemiresistive genosensor was fabricated for the early detection of Streptococcus pyogenes infection in human causing rheumatic heart disease. The mga gene of S. pyogenes specific 24 mer ssDNA probe was covalently immobilized on SWNT through a molecular bilinker, 1-pyrenemethylamine, using carbodiimide coupling reaction. The sensor was characterized by the current-voltage (I-V) characteristic curve and scanning electron microscopy. The sensing performance of the sensor was studied with respect to changes in conductance in SWNT channel based on hybridization of the target S. pyogenes single stranded genomic DNA (ssG-DNA) to its complementary 24 mer ssDNA probe. The sensor shows negligible response to non-complementary Staphylococcus aureus ssG-DNA, confirming the specificity of the sensor only with S. pyogenes. The genosensor exhibited a linear response to S. pyogenes G-DNA from 1 to1000 ng ml{sup −1} with a limit of detection of 0.16 ng ml{sup −1}.

  17. EPR analysis of cyanide complexes of wild-type human neuroglobin and mutants in comparison to horse heart myoglobin.

    Science.gov (United States)

    Van Doorslaer, Sabine; Trandafir, Florin; Harmer, Jeffrey R; Moens, Luc; Dewilde, Sylvia

    2014-06-01

    Electron paramagnetic resonance (EPR) data reveal large differences between the ferric ((13)C-)cyanide complexes of wild-type human neuroglobin (NGB) and its H64Q and F28L point mutants and the cyanide complexes of mammalian myo- and haemoglobin. The point mutations, which involve residues comprising the distal haem pocket in NGB, induce smaller, but still significant changes, related to changes in the stabilization of the cyanide ligand. Furthermore, for the first time, the full (13)C hyperfine tensor of the cyanide carbon of cyanide-ligated horse heart myoglobin (hhMb) was determined using Davies ENDOR (electron nuclear double resonance). Disagreement of these experimental data with earlier predictions based on (13)C NMR data and a theoretical model reveal significant flaws in the model assumptions. The same ENDOR procedure allowed also partial determination of the corresponding (13)C hyperfine tensor of cyanide-ligated NGB and H64QNGB. These (13)C parameters differ significantly from those of cyanide-ligated hhMb and challenge our current theoretical understanding of how the haem environment influences the magnetic parameters obtained by EPR and NMR in cyanide-ligated haem proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. NT-proBNP is associated with coronary heart disease risk in healthy older women but fails to enhance prediction beyond established risk factors: results from the British Women's Heart and Health Study.

    Science.gov (United States)

    Sattar, Naveed; Welsh, Paul; Sarwar, Nadeem; Danesh, John; Di Angelantonio, Emanuele; Gudnason, Vilmundur; Davey Smith, George; Ebrahim, Shah; Lawlor, Debbie A

    2010-03-01

    Limited evidence suggests NT-proBNP improves prediction of coronary heart disease (CHD) events but further data are needed, especially in people without pre-existing CHD and in women. We measured NT-proBNP in serum from 162 women with incident CHD events and 1226 controls (60-79 years) in a case-control study nested within the prospective British Women's Heart and Health Study. All cases and controls were free from CHD at baseline. We related NT-proBNP to CHD event risk, and determined to what extent NT-proBNP enhanced CHD risk prediction beyond established risk factors. The odds ratio for CHD per 1 standard deviation increase in log(e)NT-proBNP was 1.37 (95% CI: 1.13-1.68) in analyses adjusted for established CHD risk factors, social class, CRP and insulin. However, addition of log(e)NT-proBNP did not improve the discrimination of a prediction model including age, social class, smoking, physical activity, lipids, fasting glucose, waist:hip ratio, hypertension, statin and aspirin use, nor a standard Framingham risk score model; area under the receiver operator curve for the former model increased from 0.676 to 0.687 on inclusion of NT-proBNP (p=0.3). Furthermore, adding NT-proBNP did not improve calibration of a prediction model containing established risk factors, nor did inclusion more appropriately re-classify participants in relation to their final outcome. Findings were similar (independent associations, but no prediction improvement) for fasting insulin and CRP. These results caution against use of NT-proBNP for CHD risk prediction in healthy women and suggest a need for larger studies in both genders to resolve outstanding uncertainties.

  19. Sex-specific predictive power of 6-minute walk test in chronic heart failure is not enhanced using percent achieved of published reference equations.

    Science.gov (United States)

    Frankenstein, Lutz; Zugck, Christian; Nelles, Manfred; Schellberg, Dieter; Katus, Hugo; Remppis, Andrew

    2008-04-01

    The 6-minute walk test (6MWT) is an established prognostic tool in chronic heart failure. The strong influence of height, weight, age, and sex on 6MWT distance may be accounted for by using percentage achieved of predicted value rather than uncorrected 6MWT values. The study included 1069 patients (862 men) with a mean age 55.2 +/- 11.7 years and mean left ventricular ejection fraction of 29% +/- 10%, attending the heart failure clinic of the University of Heidelberg between 1995 and 2005. The predictive power and accuracy of 6MWT and achieved percentage values according to all available published equations for mortality and mortality or transplant combined were tested separately for each sex. The percentage values varied largely between equations. For all equations, women in New York Heart Association (NYHA) functional class I had higher values than men. Although the 6MWT significantly discriminated all NYHA classes for both sexes, only 1 equation discriminated all NYHA classes. No significant differences in the area under the receiver operating-characteristic curve were noted between achieved percentage values and 6MWT. Despite strong univariate significance, achieved percentage values did not retain multivariate significance. The 6MWT was independent from N-terminal brain natriuretic propeptide, NYHA, left ventricular ejection fraction, and peak oxygen uptake. We confirmed 6MWT to be a strong and independent risk predictor for both sexes. Because the prognostic power of 6MWT is not enhanced using percentage achieved of published reference equations, we suggest recalibration of these reference values rather than discarding this approach.

  20. The Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART).

    Science.gov (United States)

    Jernberg, Tomas; Attebring, Mona F; Hambraeus, Kristina; Ivert, Torbjorn; James, Stefan; Jeppsson, Anders; Lagerqvist, Bo; Lindahl, Bertil; Stenestrand, Ulf; Wallentin, Lars

    2010-10-01

    The aims of the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) are to support the improvement of care and evidence-based development of therapy of coronary artery disease (CAD). To provide users with online interactive reports monitoring the processes of care and outcomes and allowing direct comparisons over time and with other hospitals. National, regional and county-based reports are publicly presented on a yearly basis. Every hospital (n=74) in Sweden providing the relevant services participates. Launched in 2009 after merging four national registries on CAD. Consecutive acute coronary syndrome (ACS) patients, and patients undergoing coronary angiography/angioplasty or heart surgery. Includes approximately 80, 000 new cases each year. On admission in ACS patients, at coronary angiography in patients with stable CAD. 106 variables for patients with ACS, another 75 variables regarding secondary prevention after 12-14 months, 150 variables for patients undergoing coronary angiography/angioplasty, 100 variables for patients undergoing heart surgery. Web-based registry with all data registered online directly by the caregiver. A monitor visits approximately 20 hospitals each year. In 2007, there was a 96% agreement. Merged with the National Cause of Death Register, including information about vital status of all Swedish citizens, the National Patient Registry, containing diagnoses at discharge for all hospital stays in Sweden and the National Registry of Drug prescriptions recording all drug prescriptions in Sweden. Available for research by application to the SWEDEHEART steering group.

  1. Healthcare performance and the effects of the binaural beats on human blood pressure and heart rate.

    Science.gov (United States)

    Carter, Calvin

    2008-01-01

    Binaural beats are the differences in two different frequencies (in the range of 30-1000 Hz). Binaural beats are played through headphones and are perceived by the superior olivary nucleus of each hemisphere of the brain. The brain perceives the binaural beat and resonates to its frequency (frequency following response). Once the brain is in tune with the binaural beat it produces brainwaves of that frequency altering the listener's state of mind. In this experiment, the effects of the beta and theta binaural beat on human blood pressure and pulse were studied. Using headphones, three sounds were played for 7 minutes each to 12 participants: the control,- the sound of a babbling brook (the background sound to the two binaural beats), the beta binaural beat (20 Hz), and the theta binaural beat (7 Hz). Blood pressure and pulse were recorded before and after each sound was played. Each participant was given 2 minutes in-between each sound. The results showed that the control and the two binaural beats did not affect the 12 participant's blood pressure or pulse (p > 0.05). One reason for this may be that the sounds were not played long enough for the brain to either perceive and/or resonate to the frequency. Another reason why the sounds did not affect blood pressure and pulse may be due to the participant's age since older brains may not perceive the binaural beats as well as younger brains.

  2. Creatine kinase rate constant in the human heart measured with 3D‐localization at 7 tesla

    Science.gov (United States)

    Robson, Matthew D.; Neubauer, Stefan; Rodgers, Christopher T.

    2016-01-01

    Purpose We present a new Bloch‐Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first‐order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four‐angle saturation transfer (FAST) method using amplitude‐modulated radiofrequency pulses, phosphorus Bloch‐Siegert B1+‐mapping to determine the per‐voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Methods Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1H localization). Results BOAST kfCK values were 0.281 ± 0.002 s−1 in the calf and 0.35 ± 0.05 s−1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg−1 s−1. The sensitive volume for BOAST depends on the B1 inhomogeneity of the transmit coil. Conclusion BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10‐cm loop coil. Magn Reson Med 78:20–32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:27579566

  3. Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature

    Directory of Open Access Journals (Sweden)

    Hossain Mokarram

    2012-07-01

    Full Text Available Abstract Background Nitric oxide (NO is a multifunctional signaling molecule that regulates important cellular events in inflammation including leukocyte recruitment. Previous studies have shown that pharmacological inhibition of NO synthesis induces leukocyte recruitment in various in vitro and animal models. However, it is not known whether NO modulation has similar effects on leukocyte-endothelial cell interactions within the human microvasculature. The present study explored the effect of systemic L-NAME treatment on leukocyte recruitment in the SCID-hu mouse model. Methods Human skin xenografts were transplanted in SCID mice to study human leukocyte dynamics in human vasculature. Early events of human leukocyte recruitment in human vasculature were studied using intravital microscopy. NO synthesis was pharmacologically inhibited using NG-nitro-L-arginine methyl ester (L-NAME. Immunohistochemical analysis was performed to elucidate E-selectin expression in human xenograft skin. Human neutrophil-endothelial cell interactions were also studied in an in vitro flow chamber assay system. P- and E-selectin expression on cultured human umbilical vein endothelial cells (HUVECs was measured using ELISA. Platelet-activating factor (PAF synthesis was detected using a TLC-based assay. Results L-NAME treatment significantly enhanced the rolling and adhesion of human leukocytes to the human vasculature. Functional blocking of P- and E-selectins significantly inhibited rolling but not adhesion induced by inhibition of NO synthesis. Systemic L-NAME treatment enhanced E-selectin expression in human xenograft skin. L-NAME treatment significantly enhanced P- and E-selectin expression on HUVECs. L-NAME treatment did not significantly modify neutrophil rolling or adhesion to HUVECs indicating that L-NAME−induced subtle P- and E-selectin expression was insufficient to elicit dynamic neutrophil-HUVEC interactions in vitro. Moreover, synthesis of endothelial

  4. Vortex-ring mixing as a measure of diastolic function of the human heart: Phantom validation and initial observations in healthy volunteers and patients with heart failure.

    Science.gov (United States)

    Töger, Johannes; Kanski, Mikael; Arvidsson, Per M; Carlsson, Marcus; Kovács, Sándor J; Borgquist, Rasmus; Revstedt, Johan; Söderlind, Gustaf; Arheden, Håkan; Heiberg, Einar

    2016-06-01

    To present and validate a new method for 4D flow quantification of vortex-ring mixing during early, rapid filling of the left ventricle (LV) as a potential index of diastolic dysfunction and heart failure. 4D flow mixing measurements were validated using planar laser-induced fluorescence (PLIF) in a phantom setup. Controls (n = 23) and heart failure patients (n = 23) were studied using 4D flow at 1.5T (26 subjects) or 3T (20 subjects) to determine vortex volume (VV) and inflowing volume (VVinflow ). The volume mixed into the vortex-ring was quantified as VVmix-in = VV-VVinflow . The mixing ratio was defined as MXR = VVmix-in /VV. Furthermore, we quantified the fraction of the end-systolic volume (ESV) mixed into the vortex-ring (VVmix-in /ESV) and the fraction of the LV volume at diastasis (DV) occupied by the vortex-ring (VV/DV). PLIF validation of MXR showed fair agreement (R(2) = 0.45, mean ± SD 1 ± 6%). MXR was higher in patients compared to controls (28 ± 11% vs. 16 ± 10%, P Vortex-ring mixing can be quantified using 4D flow. The differences in mixing parameters observed between controls and patients motivate further investigation as indices of diastolic dysfunction. J. Magn. Reson. Imaging 2016;43:1386-1397. © 2015 Wiley Periodicals, Inc.

  5. Effects of n-3 fatty acids from fish on premature ventricular complexes and heart rate in humans

    NARCIS (Netherlands)

    Geelen, A.; Brouwer, I.A.; Katan, M.B.; Schouten, E.G.; Maan, A.C.; Zock, P.L.

    2005-01-01

    Background: A large body of evidence suggests that n-3 fatty acids from fish prevent fatal heart disease. They may be an effective and safe alternative to drug treatment for reducing the risk of arrhythmia and sudden cardiac death. Objective: We investigated the effect of n-3 fatty acids on heart

  6. The influence of age on N-isopropyl-p-[123I]iodoamphetamine accumulation in the human heart

    International Nuclear Information System (INIS)

    Nakajo, Masayuki; Nakabeppu, Yoshiaki; Iwashita, Shinji; Shinohara, Shinji

    1990-01-01

    Variations in heart intensity in the 30 min and 4 hr chest images of the radiolabelled lipophilic amine, N-isopropyl-p-[ 123 I]iodoamphetamine ( 123 I-IMP) were observed in 130 patients with lung diseases, aged 23 to 85 yrs. The heart intensity had a significant positive linear correlation with age (r=0.43 at 30 min, 0.66 at 4 hr). The ratio of 4 hr heart intensity to 30 min heart intensity also had a positive linear correlation (r=0.59), suggesting slower clearance of the radioactivity from the heart in older than in younger patients during this interval. Other parameters including sex, EKG findings, liver function, blood pressure, the presence of diabetes mellitus and smoking history had no relationship to heart intensity. A significant difference between heart intensities in bronchogenic carcinoma and pneumonia patient groups might be probably due to the age difference between the two groups. Therefore heart intensity in the 4 hr 123 I-IMP image may reflect certain metabolic and/or myocardial changes with aging. (author)

  7. Quality of life in patients receiving telemedicine enhanced chronic heart failure disease management: A meta-analysis.

    Science.gov (United States)

    Knox, Liam; Rahman, Rachel J; Beedie, Chris

    2017-08-01

    Background Previous reviews have investigated the effectiveness of telemedicine in the treatment of heart failure (HF). Dependent variables have included hospitalisations, mortality rates, disease knowledge and health costs. Few reviews, however, have examined the variable of health-related quality of life (QoL). Methods Randomised controlled trials comparing the delivery methods of any form of telemedicine with usual care for the provision of HF disease-management were identified via searches of all relevant databases and reference lists. Studies had to report a quantitative measure for mental, physical or overall QoL in order to be included. Results A total of 33 studies were identified. However, poor reporting of data resulted in the exclusion of seven, leaving 26 studies with 7066 participants. Three separate, random effects meta-analyses were conducted for mental, physical and overall QoL. Telemedicine was not significantly more effective than usual care on mental and physical QoL (standardised mean difference (SMD) 0.03, (95% confidence interval (CI) -0.05-0.12), p = 0.45 and SMD 0.24, (95% CI -0.08-0.56), p = 0.14, respectively). However, when compared to usual care, telemedicine was associated with a small significant increase in overall QoL (SMD 0.23, (95% CI 0.09-0.37), p = 0.001). Moderator analyses indicated that telemedicine delivered over a long-duration (≥52 weeks) and via telemonitoring was most beneficial. Conclusion Compared to usual care, telemedicine significantly increases overall QoL in patients receiving HF disease management. Statistically non-significant but nonetheless positive trends were also observed for physical QoL. These findings provide preliminary support for the use of telemedicine in the management of heart failure without jeopardising patient well-being.

  8. Heart rate informed artificial pancreas system enhances glycemic control during exercise in adolescents with T1D.

    Science.gov (United States)

    DeBoer, Mark D; Cherñavvsky, Daniel R; Topchyan, Katarina; Kovatchev, Boris P; Francis, Gary L; Breton, Marc D

    2017-11-01

    To evaluate the safety and performance of using a heart rate (HR) monitor to inform an artificial pancreas (AP) system during exercise among adolescents with type 1 diabetes (T1D). In a randomized, cross-over trial, adolescents with T1D age 13 - 18 years were enrolled to receive on separate days either the unmodified UVa AP (stdAP) or an AP system connected to a portable HR monitor (AP-HR) that triggered an exercise algorithm for blood glucose (BG) control. During admissions participants underwent a structured exercise regimen. Hypoglycemic events and CGM tracings were compared between the two admissions, during exercise and for the full 24-hour period. Eighteen participants completed the trial. While number of hypoglycemic events during exercise and rest was not different between visits (0.39 AP-HR vs 0.50 stdAP), time below 70 mg dL -1 was lower on AP-HR compared to stdAP, 0.5±2.1% vs 7.4±12.5% (P = 0.028). Time with BG within 70-180 mg dL -1 was higher for the AP-HR admission vs stdAP during the exercise portion and overall (96% vs 87%, and 77% vs 74%), but these did not reach statistical significance (P = 0.075 and P = 0.366). Heart rate signals can safely and efficaciously be integrated in a wireless AP system to inform of physical activity. While exercise contributes to hypoglycemia among adolescents, even when using an AP system, informing the system of exercise via a HR monitor improved time <70 mg dL -1 . Nonetheless, it did not significantly reduce the total number of hypoglycemic events, which were low in both groups. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Sensitivity-enhanced 13C MR spectroscopy of the human brain at 3 Tesla.

    NARCIS (Netherlands)

    Klomp, D.W.J.; Renema, W.K.J.; Graaf, M. de; Galan, B.E. de; Kentgens, A.P.M.; Heerschap, A.

    2006-01-01

    A new coil design for sensitivity-enhanced 13C MR spectroscopy (MRS) of the human brain is presented. The design includes a quadrature transmit/receive head coil optimized for 13C MR sensitivity. Loss-less blocking circuits inside the coil conductors allow this coil to be used inside a homogeneous

  10. Sensitivity-enhanced C-13 MR spectroscopy of the human brain at 3 Tesla

    NARCIS (Netherlands)

    Klomp, D.W.J.; Renema, W.K.J.; Graaf, M. van der; Galan, B.E. de; Kentgens, A.P.M.; Heerschap, A.

    2006-01-01

    A new coil design for sensitivity-enhanced C-13 MR spectroscopy (MRS) of the human brain is presented. The design includes a quadrature transmit/receive head coil optimized for C-13 MR sensitivity. Loss-less blocking circuits inside the coil conductors allow this coil to be used inside a homogeneous

  11. Light-enhanced inhibition of ouabain binding to digitalis receptor in rat brain and guinea pig heart by the food dye erythrosine

    International Nuclear Information System (INIS)

    Hnatowich, M.; LaBella, F.S.

    1982-01-01

    Erythrosine (ERY) (FD and C red no. 3) inhibited specific binding of [ 3 H]ouabain to rat brain homogenates with an IC50 of 23 microM in the dark and 1 microM in ordinary fluorescent light. Competition studies demonstrated the presence of two components, only one of which was affected by light. Lineweaver-Burk analysis indicated that ERY preferentially antagonizes [ 3 H]ouabain binding at a high-affinity site in the light, whereas in the dark the dye inhibits binding in a manner qualitatively similar to inhibition by ouabain. Light enhancement of ERY potency occurred only when dye and tissue were present together in the incubation medium, pointing to participation of transient molecular species. However, neither superoxide dismutase nor catalase altered the effects of ERY in the light or dark, suggesting the absence of oxygen free radicals. When oxygen levels were raised, there was enhancement of inhibition by ERY at a high-affinity receptor accompanied by disappearance of [ 3 H]ouabain binding at one of lower affinity. In contrast to brain, membranes from guinea pig heart showed only one binding site for [ 3 H]ouabain, and antagonism by ERY at this site was markedly enhanced by light. Structural differences between classes of ouabain binding regions probably accounts for the discrimination exhibited by ERY in the presence of light and oxygen. Our findings also caution that metabolic transformation of this common food dye, light decomposition, or photoreaction with foodstuff may yield more toxic derivatives

  12. Nicotine Acutely Enhances Reinforcement from Non-Drug Rewards in Humans

    Directory of Open Access Journals (Sweden)

    Kenneth A. Perkins

    2017-05-01

    Full Text Available Preclinical research documents that, aside from the primary and secondary reinforcing effects of nicotine intake itself, nicotine also acutely enhances the reinforcing efficacy of non-drug reinforcers (“rewards”. Study of these effects in humans has largely been overlooked, but very recent findings suggest they may have clinical implications for more fully understanding the persistence of tobacco dependence. This overview first outlines the topic and notes some recent human studies indirectly addressing nicotine effects on related responses (e.g., subjective ratings, explaining why those findings do not directly confirm enhancement of behavioral reinforcement per se due to nicotine. Then, the methodology used in the subsequently presented studies is described, demonstrating how those studies specifically did demonstrate enhancement of reinforced responding for non-drug rewards. The main section focuses on the limited controlled research to date directly assessing nicotine’s acute reinforcement-enhancing effects in humans, particularly as it relates to reinforced behavioral responding for non-drug rewards in non-human animal models. After detailing those few existing human studies, we address potential consequences of these effects for dependence and tobacco cessation efforts and then suggest directions for future research. This research indicates that nicotine per se increases responding in humans that is reinforced by some rewards (auditory stimuli via music, visual stimuli via video, but perhaps not by others (e.g., money. These reinforcement-enhancing effects in smokers are not due to dependence or withdrawal relief and can be restored by a small amount of nicotine (similar to a smoking lapse, including from e-cigarettes, a non-tobacco nicotine product. Future clinical research should examine factors determining which types of rewards are (or are not enhanced by nicotine, consequences of the loss of these nicotine effects after quitting

  13. Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion

    Directory of Open Access Journals (Sweden)

    Khayat Andre

    2011-01-01

    Full Text Available Abstract We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.

  14. Enhanced capacity of DNA repair in human cytomegalovirus-infected cells

    International Nuclear Information System (INIS)

    Nishiyama, Y.; Rapp, F.

    1981-01-01

    Plaque formation in Vero cells by UV-irradiated herpes simplex virus was enhanced by infection with human cytomegalovirus (HCMV), UV irradiation, or treatment with methylmethanesulfonate. Preinfection of Vero cells with HCMV enhanced reactivation of UV-irradiated herpes simplex virus more significantly than did treatment with UV or methylmethanesulfonate alone. A similar enhancement by HCMV was observed in human embryonic fibroblasts, but not in xeroderma pigmentosum (XP12BE) cells. It was also found that HCMV infection enhanced hydroxyurea-resistant DNA synthesis induced by UV light or methylmethanesulfonate. Alkaline sucrose gradient sedimentation analysis revealed an enhanced rate of synthesis of all size classes of DNA in UV-irradiated HCMV-infected Vero cells. However, HCMV infection did not induce repairable lesions in cellular DNA and did not significantly inhibit host cell DNA synthesis, unlike UV or methylmethanesulfonate. These results indicate that HCMV enhanced DNA repair capacity in the host cells without producing detectable lesions in cellular DNA and without inhibiting DNA synthesis. This repair appeared to be error proof for UV-damaged herpes simplex virus DNA when tested with herpes simplex virus thymidine kinase-negative mutants

  15. Teaching medical humanities in the digital world: affordances of technology-enhanced learning.

    Science.gov (United States)

    Kemp, Sandra Joy; Day, Giskin

    2014-12-01

    Medical humanities courses are typically taught in face-to-face teaching environments, but now medical humanities educators, alongside educators from other disciplines, are facing shifts in higher education towards online (and sometimes open) courses. For the medical humanities educator, there is limited guidance regarding how technology-enhanced learning design can support the learning outcomes associated with medical humanities. This article aims to provide useful direction for such educators on how digital technologies can be used through learner-focused pedagogies. Specific examples are provided as to how the affordances of Web 2.0 and other tools can be realised in innovative ways to help achieve skills development within the medical humanities. The guidance, alongside the practical suggestions for implementation, can provide important conceptual background for medical humanities educators who wish to embrace technology-enhanced learning, and reconceptualise or redesign medical humanities for an online or blended teaching environment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Distinctiveness enhances long-term event memory in non-human primates, irrespective of reinforcement.

    Science.gov (United States)

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-08-01

    Non-human primates are capable of recalling events that occurred as long as 3 years ago, and are able to distinguish between similar events; akin to human memory. In humans, distinctiveness enhances memory for events, however, it is unknown whether the same occurs in non-human primates. As such, we tested three great ape species on their ability to remember an event that varied in distinctiveness. Across three experiments, apes witnessed a baiting event in which one of three identical containers was baited with food. After a delay of 2 weeks, we tested their memory for the location of the baited container. Apes failed to recall the baited container when the event was undistinctive (Experiment 1), but were successful when it was distinctive (Experiment 2), although performance was equally good in a less-distinctive condition. A third experiment (Experiment 3) confirmed that distinctiveness, independent of reinforcement, was a consistent predictor of performance. These findings suggest that distinctiveness may enhance memory for events in non-human primates in the same way as in humans, and provides further evidence of basic similarities between the ways apes and humans remember past events. © 2017 Wiley Periodicals, Inc.

  17. Human engineering design considerations for the use of signal color enhancement in ASW displays

    Energy Technology Data Exchange (ETDEWEB)

    Banks, W.W.

    1990-11-01

    The Lawrence Livermore National Laboratory (LLNL) was requested to examine and define man-machine limits as part of the Office of Naval Technology's High Gain Initiative program (HGI). As an initial investigative area, LLNL's Systems and Human Performance effort focused upon color display interfaces and the use of color enhancement techniques to define human and system interface limits in signal detection and discrimination tasks. The knowledgeable and prudent use of color in different types of display is believed to facilitate human visual detection, discrimination and recognition in complex visual tasks. The consideration and understanding of the complex set of interacting variables associated with the prudent use of color is essential to optimize human performance, especially in the ASW community. The designers of advanced display technology and signal processing algorithms may be eventually called upon to present pre-processed information to ASW operators and researchers using the latest color enhancement techniques. These techniques, however, may be limited if one does not understand the complexity and limits of human information processing which reflects the assessed state of knowledge relevant to the use of color in displays. The initial sections of this report discuss various aspects of color presentation and the problems typically encountered, while the last section deals with a specific research proposal required to further our understanding and proper use of color enhancement methods.

  18. The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts.

    Science.gov (United States)

    Schultz, Francisca; Hasan, Alveera; Alvarez-Laviada, Anita; Miragoli, Michele; Bhogal, Navneet; Wells, Sarah; Poulet, Claire; Chambers, Jenny; Williamson, Catherine; Gorelik, Julia

    2016-01-01

    Bile acids are elevated in the blood of women with intrahepatic cholestasis of pregnancy (ICP) and this may lead to fetal arrhythmia, fetal hypoxia and potentially fetal death in utero. The bile acid taurocholic acid (TC) causes abnormal calcium dynamics and contraction in neonatal rat cardiomyocytes. Ursodeoxycholic acid (UDCA), a drug clinically used to treat ICP, prevents adverse effects of TC. During development, the fetus is in a state of relative hypoxia. Although this is essential for the development of the heart and vasculature, resident fibroblasts can transiently differentiate into myofibroblasts and form gap junctions with cardiomyocytes in vitro, resulting in cardiomyocyte depolarization. We expanded on previously published work using an in vitro hypoxia model to investigate the differentiation of human fetal fibroblasts into myofibroblasts. Recent evidence shows that potassium channels are involved in maintaining the membrane potential of ventricular fibroblasts and that ATP-dependent potassium (KATP) channel subunits are expressed in cultured fibroblasts. KATP channels are a valuable target as they are thought to have a cardioprotective role during ischaemic and hypoxic conditions. We investigated whether UDCA could modulate fibroblast membrane potential. We established the isolation and culture of human fetal cardiomyocytes and fibroblasts to investigate the effect of hypoxia, TC and UDCA on human fetal cardiac cells. UDCA hyperpolarized myofibroblasts and prevented TC-induced depolarisation, possibly through the activation of KATP channels that are expressed in cultured fibroblasts. Also, similar to the rat model, UDCA can counteract TC-induced calcium abnormalities in human fetal cultures of cardiomyocytes and myofibroblasts. Under normoxic conditions, we found a higher number of myofibroblasts in cultures derived from human fetal hearts compared to cells isolated from neonatal rat hearts, indicating a possible increased number of myofibroblasts

  19. Embryonic and foetal Islet-1 positive cells in human hearts are also positive to c-Kit

    Directory of Open Access Journals (Sweden)

    C. Serradifalco

    2011-12-01

    Full Text Available During embryogenesis, the mammalian heart develops from a primitive heart tube originating from two bilateral primary heart fields located in the lateral plate mesoderm. Cells belongings to the pre-cardiac mesoderm will differentiate into early cardiac progenitors, which express early transcription factors which are also common to the Isl-1 positive cardiac progenitor cells isolated from the developing pharyngeal mesoderm and the foetal and post-natal mice hearts. A second population of cardiac progenitor cells positive to c-Kit has been abundantly isolated from adult hearts. Until now, these two populations have been considered two different sets of progenitor cells present in the heart in different stages of an individual life. In the present study we collected embryonic, foetal and infant hearts, and we tested the hypotheses that c-Kit positive cells, usually isolated from the adult heart, are also present in the intra-uterine life and persist in the adult heart after birth, and that foetal Isl-1 positive cells are also positive to c-Kit. Using immunohistochemistry we studied the temporal distribution of Isl-1 positive and c-Kit/CD105 double positive cells, and by immunofluorescence and confocal analysis we studied the co-localization of c-Kit and Isl-1 positive cells. The results indicated that cardiomyocytes and interstitial cells were positive for c-Kit from the 9th to the 19th gestational week, that cells positive for both c-Kit and CD105 appeared in the interstitium at the 17th gestational week and persisted in the postnatal age, and that the Isl-1 positive cells were a subset of the c-Kit positive population.

  20. Prospective Heart Tracking for Whole-heart Magnetic Resonance Angiography

    Science.gov (United States)

    Moghari, Mehdi H.; Geva, Tal; Powell, Andrew J.

    2015-01-01

    Purpose To develop a prospective respiratory-gating technique (Heart-NAV) for use with contrast-enhanced 3D inversion recovery (IR) whole-heart magnetic resonance angiography (MRA) acquisitions that directly tracks heart motion without creating image inflow artifact. Methods With Heart-NAV, 1 of the startup pulses for the whole-heart steady-state free precession MRA sequence is used to collect the centerline of k-space, and its 1-dimensional reconstruction is fed into the standard diaphragm-navigator (NAV) signal analysis process to prospectively gate and track respiratory-induced heart displacement. Ten healthy volunteers underwent non-contrast whole-heart MRA acquisitions using the conventional diaphragm-NAV and Heart-NAV with 5 and 10 mm acceptance windows in a 1.5T scanner. Five patients underwent contrast-enhanced IR whole-heart MRA using a diaphragm-NAV and Heart-NAV with a 5 mm acceptance window. Results For non-contrast whole-heart MRA with both the 5 and 10 mm acceptance windows, Heart-NAV yielded coronary artery vessel sharpness and subjective visual scores that were not significantly different than those using a conventional diaphragm-NAV. Scan time for Heart-NAV was 10% shorter (p<0.05). In patients undergoing contrast-enhanced IR whole-heart MRA, inflow artifact was seen with the diaphragm-NAV but not with Heart-NAV. Conclusion Compared to a conventional diaphragm-NAV, Heart-NAV achieves similar image quality in a slightly shorter scan time and eliminates inflow artifact. PMID:26843458

  1. Heart Diseases

    Science.gov (United States)

    ... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...

  2. Heart Transplantation

    Science.gov (United States)

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes from a donor who has died. It is the last resort for people with heart failure when all other treatments have failed. The ...

  3. Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans

    NARCIS (Netherlands)

    Silvani, A.; Calandra-Buonaura, G.; Johnson, B.D.; Helmond, N. van; Barletta, G.; Cecere, A.G.; Joyner, M.J.; Cortelli, P.

    2017-01-01

    The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological

  4. Creatine kinase rate constant in the human heart measured with 3D-localization at 7 tesla.

    Science.gov (United States)

    Clarke, William T; Robson, Matthew D; Neubauer, Stefan; Rodgers, Christopher T

    2017-07-01

    We present a new Bloch-Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first-order effective rate constant k f in human myocardium at 7 tesla (T). BOAST combines a variant of the four-angle saturation transfer (FAST) method using amplitude-modulated radiofrequency pulses, phosphorus Bloch-Siegert B1+-mapping to determine the per-voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1 H localization). BOAST kfCK values were 0.281 ± 0.002 s -1 in the calf and 0.35 ± 0.05 s -1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg -1 s -1 . The sensitive volume for BOAST depends on the B 1 inhomogeneity of the transmit coil. BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10-cm loop coil. Magn Reson Med 78:20-32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  5. Light-enhanced inhibition of ouabain binding to digitalis receptor in rat brain and guinea pig heart by the food dye erythrosine

    International Nuclear Information System (INIS)

    Hnatowich, M.; LaBella, F.S.

    1982-01-01

    Erythrosine (ERY) (FD and C red no. 3) inhibited specific binding of [ 3 H]ouabain to rat brain homogenates with an IC50 of 23 mM in the dark and 1 mM in ordinary fluorescent light. Competition studies demonstrated the presence of two components, only one of which was affected by light. Lineweaver-Burk analysis indicated that ERY preferentially antagonizes [ 3 H]ouabain binding at a high-affinity site in the light, whereas in the dark the dye inhibits binding in a manner qualitatively similar to inhibition by ouabain. Light enhancement of ERY potency occurred only when dye and tissue were present together in the incubation medium, pointing to participation of transient molecular species. However, neither superoxide dismutase nor catalase altered the effects of ERY in the light or dark, suggesting the absence of oxygen free radicals. In contrast to brain, membranes from guinea pig heart showed only one binding site for [ 3 H]ouabain, and antagonism by ERY at this site was markedly enhanced by light. Structural differences between classes of ouabain binding regions probably accounts for the discrimination exhibited by ERY in the presence of light and oxygen. Our findings also caution that metabolic transformation of this common food dye, light decomposition, or photoreaction with foodstuff may yield more toxic derivatives

  6. Caffeine enhancement of x-ray killing in cultured human and rodent cells

    International Nuclear Information System (INIS)

    Waldren, C.A.; Rasko, I.

    1978-01-01

    A 16 to 20 hr postirradiation incubation with caffeine enhances x-ray killing of rodent and human cells. Cells tested were Chinese hamster ovary (CHO-K1), lung (CHL), V79, mouse L, HeLa S3, human fibroblasts (AF288, TC171, FS9, CRL1166), and a human-hamster hybrid. The effect of caffeine on the x-ray survival curve of these cells was to remove the initial shoulder without significantly altering the mean lethal dose (D 0 ). This action can be achieved at caffeine concentrations which of themselves cause less than 15% killing. In randomly growing CHO-K1 cells the caffeine-sensitive process occurs with a half-time of 2 to 5 hr after irradiation. These experiments indicate the existence in human and rodent cells of caffeine-inhibited genome repair for x-ray damage

  7. INPO Perspectives and Activities to Enhance Supplier Human Performance and Safety Culture

    International Nuclear Information System (INIS)

    Duncan, R. J.

    2016-01-01

    Within their own organizations, utilities have made significant improvements in human performance and safety culture, supported by a strong community of practice through INPO and WANO. In recent years, utilities have been making increasing use of suppliers for design, construction, inspection and maintenance services in support of their NPPs. Many of these suppliers do not have the benefit of being members of a community of practice when it comes to human performance and safety culture. To help the supplier community make improvements similar to what the utilities have achieved, INPO has recently expanded its Supplier Participant program to address the issue of human performance and safety culture in the supplier community. The intent of this paper will be to share the INPO’s perspectives and activities in helping suppliers of services and products to NPPs enhance their human performance and safety culture. (author)

  8. Titanium phosphate glass microcarriers induce enhanced osteogenic cell proliferation and human mesenchymal stem cell protein expression

    Directory of Open Access Journals (Sweden)

    Nilay J Lakhkar

    2015-11-01

    Full Text Available In this study, we have developed 50- to 100-µm-sized titanium phosphate glass microcarriers (denoted as Ti5 that show enhanced proliferation of human mesenchymal stem cells and MG63 osteosarcoma cells, as well as enhanced human mesenchymal stem cell expression of bone differentiation markers, in comparison with commercially available glass microspheres at all time points. We also demonstrate that these microcarriers provide superior human mesenchymal stem cell proliferation with conventional Dulbecco’s Modified Eagle medium than with a specially developed commercial stem cell medium. The microcarrier proliferative capacity is revealed by a 24-fold increase in MG63 cell numbers in spinner flask bioreactor studies performed over a 7-day period, versus only a 6-fold increase in control microspheres under the same conditions; the corresponding values of Ti5 and control microspheres under static culture are 8-fold and 7-fold, respectively. The capability of guided osteogenic differentiation is confirmed by ELISAs for bone morphogenetic protein-2 and osteopontin, which reveal significantly greater expression of these markers, especially osteopontin, by human mesenchymal stem cells on the Ti5 microspheres than on the control. Scanning electron microscopy and confocal laser scanning microscopy images reveal favorable MG63 and human mesenchymal stem cell adhesion on the Ti5 microsphere surfaces. Thus, the results demonstrate the suitability of the developed microspheres for use as microcarriers in bone tissue engineering applications.

  9. Technology and Research Requirements for Combating Human Trafficking: Enhancing Communication, Analysis, Reporting, and Information Sharing

    Energy Technology Data Exchange (ETDEWEB)

    Kreyling, Sean J.; West, Curtis L.; Olson, Jarrod

    2011-03-17

    DHS’ Science & Technology Directorate directed PNNL to conduct an exploratory study on the domain of human trafficking in the Pacific Northwest in order to examine and identify technology and research requirements for enhancing communication, analysis, reporting, and information sharing – activities that directly support efforts to track, identify, deter, and prosecute human trafficking – including identification of potential national threats from smuggling and trafficking networks. This effort was conducted under the Knowledge Management Technologies Portfolio as part of the Integrated Federal, State, and Local/Regional Information Sharing (RISC) and Collaboration Program.

  10. Enhancing the NCSU PULSTAR reactor control room with human factors considerations

    International Nuclear Information System (INIS)

    Glover, B.L.; Pupons, D.E.; Perez, P.B.

    1993-01-01

    The North Carolina PULSTAR research reactor was constructed to support teaching, training, and research. The training provided is not limited to academic students but encompasses plant operators, managers, engineers, designers, and supporting organizations in the nuclear industry. Our facility is under-going design changes to maximize teaching effectiveness and continued safe operation by providing current technology in the control room. The opportunity for the enhancements is a result of the generosity of neighboring utilities and the US Department of Energy instrumentation upgrade funds. Our objective, to provide a control room environment that conforms to selected industry practices, required human factors input. A human factors course, offered jointly between the industrial engineering and the psychology departments, included the PULSTAR control room enhancement as a case study

  11. MMI design of K-CPS for preventing human errors and enhancing convenient operation

    International Nuclear Information System (INIS)

    Sung, Chan Ho; Jung, Yeon Sub; Oh, Eoung Se; Shin, Young Chul; Lee, Yong Kwan

    2001-01-01

    In order to supplement defects of paper procedure, reduce human errors and enhance convenient operation, computer-based procedure system is being developed. CPS (Computerized Procedure System) including human-factor engineering design concept for KNGR (Korean Next Generation Reactor) has been also developed with the same object. K-CPS(KNGR CPS) has higher level of automation than paper procedure. It is fully integrated with control and monitoring systems. Combining statements and relevant components, which changes dynamically according to plant status enhances readability of procedure. This paper shows general design criteria on computer-based procedure system, the MMI design characteristics of K-CPS and the results of suitability evaluation for K-CPS by operator

  12. Preliminary study of 3.0 T contrast-enhanced whole heart coronary MR angiography using 32-channel coils with high acceleration factor

    International Nuclear Information System (INIS)

    Yang Qi; Li Kuncheng; Du Xiangying; Ma Heng; An Jing; Li Han; Xu Dong; Bi Xiaoming; Li Debiao

    2010-01-01

    Objective: To evaluate the diagnostic accuracy of 3.0 T contrast enhanced (CE) whole-heart coronary MRA (CE MRA) using 32-channel coils with high acceleration factor. Methods: Sixty patients with suspected coronary artery disease who were scheduled for coronary angiography (CAG) underwent CE CMRA at 3.0 T MRI scanner. A 32-channel receiver coil was used for data acquisition. For image acquisition, an ECG triggered,navigator-gated, inversion-recovery prepared, segmented gradient-echo sequence was used with an acceleration factor of three in the phase-encoding direction using GRAPPA reconstruction. Gd-BOPTA (0.15 mmol/kg body weight) was intravenously administered at a rate of 0.3 ml/s. The diagnostic accuracy in detecting significant stenoses (≥50% of vessel lumen) was evaluated using χ 2 test with X-ray angiography as the reference. Results: Whole-heart CE CMRA was successfully completed in 56 patients who were scheduled for CAG. The averaged imaging time was (6.0±1.3) min. 3.0 T CE CMRA using 32 channel coils correctly identified significant CAD in 28 patients and correctly ruled out CAD in 23 patients. The sensitivity and specificity were 93.3% and 88.5% respectively. Conclusion: Combined with dedicated 32-channel coils, 3.0 T CE CMRA allows significant reduction in imaging speed and reduced dose of the contrast agent. These improvements resulted in substantially improved overall accuracy of CE CMRA in detecting coronary artery disease. (authors)

  13. Late Gadolinium Enhancement Amount as an Independent Risk Factor for the Incidence of Adverse Cardiovascular Events in Patients with Stage C or D Heart Failure

    Directory of Open Access Journals (Sweden)

    Tong Liu

    2016-10-01

    Full Text Available Background Myocardial fibrosis (MF is a risk factor for poor prognosis in dilated cardiomyopathy (DCM. Late gadolinium enhancement (LGE of the myocardium on cardiac magnetic resonance (CMR represents MF. We examined whether the LGE amount increases the incidence of adverse cardiovascular events in patients with stage C or D heart failure (HF. Methods Eighty-four consecutive patients with stage C or D HF, either ischemic or non-ischemic, were enrolled. Comprehensive clinical and CMR evaluations were performed. All patients were followed up for a composite endpoint of cardiovascular death, heart transplantation, and cardiac resynchronization therapy with defibrillator (CRT-D.Results LGE was present in 79.7% of the end-stage HF patients. LGE distribution patterns were mid-wall, epi-myocardial, endo-myocardial, and the morphological patterns were patchy, transmural, and diffuse. During the average follow-up of 544 days, 13 (15.5% patients had endpoint events: 7 patients cardiac death, 2 patients heart transplantation, and 4 patients underwent CRT-D implantation. On univariate analysis, LGE quantification on cardiac magnetic resonance, blood urine nitrogen, QRS duration on electrocardiogram, left ventricular end-diastolic diameter (LVEDD and left ventricular end-diastolic volume (LVEDV on CMR had the strongest associations with the composite endpoint events. However, on multivariate analysis for both Model I (after adjusting for age, sex, and body mass index and Model II (after adjusting for age, sex, BMI, renal function, QRS duration and atrial fibrillation on electrocardiogram, the etiology of HF, LVEF, CMR-LVEDD and CMR-LVEDV, LGE amount was a significant risk factor for composite endpoint events (Model I 6SD HR 1.037, 95%CI 1.005-1.071, p=0.022; Model II 6SD HR 1.045, 95%CI 1.001-1.084, p=0.022. Conclusion LGE amount from high-scale threshold on CMR increased the incidence of adverse cardiovascular events for patients in either stage C or D HF.

  14. A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure.

    Directory of Open Access Journals (Sweden)

    Noritoshi Fukushima

    Full Text Available Infusion of bone marrow-derived mononuclear cells (BMMNC has been reported to ameliorate cardiac dysfunction after acute myocardial infarction. In this study, we investigated whether infusion of BMMNC is also effective for non-ischemic heart failure model mice and the underlying mechanisms. Intravenous infusion of BMMNC showed transient cardioprotective effects on animal models with dilated cardiomyopathy (DCM without their engraftment in heart, suggesting that BMMNC infusion improves cardiac function via humoral factors rather than their differentiation into cardiomyocytes. Using conditioned media from sorted BMMNC, we found that the cardioprotective effects were mediated by growth hormone (GH secreted from myeloid (Gr-1(+ cells and the effects was partially mediated by signal transducer and activator of transcription 3 in cardiomyocytes. On the other hand, the GH expression in Gr-1(+ cells was significantly downregulated in DCM mice compared with that in healthy control, suggesting that the environmental cue in heart failure might suppress the Gr-1(+ cells function. Activin A was upregulated in the serum of DCM models and induced downregulation of GH levels in Gr-1(+ cells and serum. Furthermore, humoral factors upregulated in heart failure including angiotensin II upregulated activin A in peripheral blood mononuclear cells (PBMNC via activation of NFκB. Similarly, serum activin A levels were also significantly higher in DCM patients with heart failure than in healthy subjects and the GH levels in conditioned medium from PBMNC of DCM patients were lower than that in healthy subjects. Inhibition of activin A increased serum GH levels and improved cardiac function of DCM model mice. These results suggest that activin A causes heart failure by suppressing GH activity and that inhibition of activin A might become a novel strategy for the treatment of heart failure.

  15. From Shuttle Main Engine to the Human Heart: A Presentation to the Federal Lab Consortium for Technology Transfer

    Science.gov (United States)

    Fogarty, Jennifer A.

    2010-01-01

    A NASA engineer received a heart transplant performed by Drs. DeBakey and Noon after suffering a serious heart attack. 6 months later that engineer returned to work at NASA determined to use space technology to help people with heart disease. A relationship between NASA and Drs. DeBakey and Noon was formed and the group worked to develop a low cost, low power implantable ventricular assist device (VAD). NASA patented the method to reduce pumping damage to red blood cells and the design of a continuous flow heart pump (#5,678,306 and #5,947,892). The technology and methodology were licensed exclusively to MicroMed Technology, Inc.. In late 1998 MicroMed received international quality and electronic certifications and began clinical trials in Europe. Ventricular assist devices were developed to bridge the gap between heart failure and transplant. Early devices were cumbersome, damaged red blood cells, and increased the risk of developing dangerous blood clots. Application emerged from NASA turbopump technology and computational fluid dynamics analysis capabilities. To develop the high performance required of the Space Shuttle main engines, NASA pushed the state of the art in the technology of turbopump design. NASA supercomputers and computational fluid dynamics software developed for use in the modeling analysis of fuel and oxidizer flow through rocket engines was used in the miniaturization and optimization of a very small heart pump. Approximately 5 million people worldwide suffer from chronic heart failure at a cost of 40 billion dollars In the US, more than 5000 people are on the transplant list and less than 3000 transplants are performed each year due to the lack of donors. The success of ventricular assist devices has led to an application as a therapeutic destination as well as a bridge to transplant. This success has been attributed to smaller size, improved efficiency, and reduced complications such as the formation of blood clots and infection.

  16. Enhanced skin permeation of naltrexone by pulsed electromagnetic fields in human skin in vitro.

    Science.gov (United States)

    Krishnan, Gayathri; Edwards, Jeffrey; Chen, Yan; Benson, Heather A E

    2010-06-01

    The aim of the present study was to evaluate the skin permeation of naltrexone (NTX) under the influence of a pulsed electromagnetic field (PEMF). The permeation of NTX across human epidermis and a silicone membrane in vitro was monitored during and after application of the PEMF and compared to passive application. Enhancement ratios of NTX human epidermis permeation by PEMF over passive diffusion, calculated based on the AUC of cumulative NTX permeation to the receptor compartment verses time for 0-4 h, 4-8 h, and over the entire experiment (0-8 h) were 6.52, 5.25, and 5.66, respectively. Observation of the curve indicated an initial enhancement of NTX permeation compared to passive delivery whilst the PEMF was active (0-4 h). This was followed by a secondary phase after termination of PEMF energy (4-8 h) in which there was a steady increase in NTX permeation. No significant enhancement of NTX penetration across silicone membrane occurred with PEMF application in comparison to passively applied NTX. In a preliminary experiment PEMF enhanced the penetration of 10 nm gold nanoparticles through the stratum corneum as visualized by multiphoton microscopy. This suggests that the channels through which the nanoparticles move must be larger than the 10 nm diameter of these rigid particles. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  17. Science fiction and human enhancement: radical life-extension in the movie 'In Time' (2011).

    Science.gov (United States)

    Roduit, Johann A R; Eichinger, Tobias; Glannon, Walter

    2018-03-20

    The ethics of human enhancement has been a hotly debated topic in the last 15 years. In this debate, some advocate examining science fiction stories to elucidate the ethical issues regarding the current phenomenon of human enhancement. Stories from science fiction seem well suited to analyze biomedical advances, providing some possible case studies. Of particular interest is the work of screenwriter Andrew Niccol (Gattaca, S1m0ne, In Time, and Good Kill), which often focuses on ethical questions raised by the use of new technologies. Examining the movie In Time (2011), the aim of this paper is to show how science fiction can contribute to the ethical debate of human enhancement. In Time provides an interesting case study to explore what could be some of the consequences of radical life-extension technologies. In this paper, we will show how arguments regarding radical life-extension portrayed in this particular movie differ from what is found in the scientific literature. We will see how In Time gives flesh to arguments defending or rejecting radical life-extension. It articulates feelings of unease, alienation and boredom associated with this possibility. Finally, this article will conclude that science fiction movies in general, and In Time in particular, are a valuable resource for a broad and comprehensive debate about our coming future.

  18. Low Doses of Ethanol Enhance LTD-like Plasticity in Human Motor Cortex.

    Science.gov (United States)

    Fuhl, Anna; Müller-Dahlhaus, Florian; Lücke, Caroline; Toennes, Stefan W; Ziemann, Ulf

    2015-12-01

    Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks.

  19. National Heart, Lung, and Blood Institute Workshop Summary: Enhancing Opportunities for Training and Retention of a Diverse Biomedical Workforce.

    Science.gov (United States)

    Duncan, Gregg A; Lockett, Angelia; Villegas, Leah R; Almodovar, Sharilyn; Gomez, Jose L; Flores, Sonia C; Wilkes, David S; Tigno, Xenia T

    2016-04-01

    Committed to its mission of conducting and supporting research that addresses the health needs of all sectors of the nation's population, the Division of Lung Diseases, National Heart, Lung, and Blood Institute of the National Institutes of Health (NHLBI/NIH) seeks to identify issues that impact the training and retention of underrepresented individuals in the biomedical research workforce. Early-stage investigators who received grant support through the NIH Research Supplements to Promote Diversity in Health Related Research Program were invited to a workshop held in Bethesda, Maryland in June, 2015, in order to (1) assess the effectiveness of the current NHLBI diversity program, (2) improve its strategies towards achieving its goal, and (3) provide guidance to assist the transition of diversity supplement recipients to independent NIH grant support. Workshop participants participated in five independent focus groups to discuss specific topics affecting underrepresented individuals in the biomedical sciences: (1) Socioeconomic barriers to success for diverse research scientists; (2) role of the academic research community in promoting diversity; (3) life beyond a research project grant: non-primary investigator career paths in research; (4) facilitating career development of diverse independent research scientists through NHLBI diversity programs; and (5) effectiveness of current NHLBI programs for promoting diversity of the biomedical workforce. Several key issues experienced by young, underrepresented biomedical scientists were identified, and solutions were proposed to improve on training and career development for diverse students, from the high school to postdoctoral trainee level, and address limitations of currently available diversity programs. Although some of the challenges mentioned, such as cost of living, limited parental leave, and insecure extramural funding, are also likely faced by nonminority scientists, these issues are magnified among diversity

  20. Electrical noise modulates perception of electrical pulses in humans: sensation enhancement via stochastic resonance.

    Science.gov (United States)

    Iliopoulos, Fivos; Nierhaus, Till; Villringer, Arno

    2014-03-01

    Although noise is usually considered to be harmful for signal detection and information transmission, stochastic resonance (SR) describes the counterintuitive phenomenon of noise enhancing the detection and transmission of weak input signals. In mammalian sensory systems, SR-related phenomena may arise both in the peripheral and the central nervous system. Here, we investigate behavioral SR effects of subliminal electrical noise stimulation on the perception of somatosensory stimuli in humans. We compare the likelihood to detect near-threshold pulses of different intensities applied on the left index finger during presence vs. absence of subliminal noise on the same or an adjacent finger. We show that (low-pass) noise can enhance signal detection when applied on the same finger. This enhancement is strong for near-threshold pulses below the 50% detection threshold and becomes stronger when near-threshold pulses are applied as brief trains. The effect reverses at pulse intensities above threshold, especially when noise is replaced by subliminal sinusoidal stimulation, arguing for a peripheral direct current addition. Unfiltered noise applied on longer pulses enhances detection of all pulse intensities. Noise applied to an adjacent finger has two opposing effects: an inhibiting effect (presumably due to lateral inhibition) and an enhancing effect (most likely due to SR in the central nervous system). In summary, we demonstrate that subliminal noise can significantly modulate detection performance of near-threshold stimuli. Our results indicate SR effects in the peripheral and central nervous system.

  1. Attention Determines Contextual Enhancement versus Suppression in Human Primary Visual Cortex.

    Science.gov (United States)

    Flevaris, Anastasia V; Murray, Scott O

    2015-09-02

    Neural responses in primary visual cortex (V1) depend on stimulus context in seemingly complex ways. For example, responses to an oriented stimulus can be suppressed when it is flanked by iso-oriented versus orthogonally oriented stimuli but can also be enhanced when attention is directed to iso-oriented versus orthogonal flanking stimuli. Thus the exact same contextual stimulus arrangement can have completely opposite effects on neural responses-in some cases leading to orientation-tuned suppression and in other cases leading to orientation-tuned enhancement. Here we show that stimulus-based suppression and enhancement of fMRI responses in humans depends on small changes in the focus of attention and can be explained by a model that combines feature-based attention with response normalization. Neurons in the primary visual cortex (V1) respond to stimuli within a restricted portion of the visual field, termed their "receptive field." However, neuronal responses can also be influenced by stimuli that surround a receptive field, although the nature of these contextual interactions and underlying neural mechanisms are debated. Here we show that the response in V1 to a stimulus in the same context can either be suppressed or enhanced depending on the focus of attention. We are able to explain the results using a simple computational model that combines two well established properties of visual cortical responses: response normalization and feature-based enhancement. Copyright © 2015 the authors 0270-6474/15/3512273-08$15.00/0.

  2. Protease inhibitors enhance extracellular collagen fibril deposition in human mesenchymal stem cells.

    Science.gov (United States)

    Han, Sejin; Li, Yuk Yin; Chan, Barbara Pui

    2015-10-15

    Collagen is a widely used naturally occurring biomaterial for scaffolding, whereas mesenchymal stem cells (MSCs) represent a promising cell source in tissue engineering and regenerative medicine. It is generally known that cells are able to remodel their environment by simultaneous degradation of the scaffolds and deposition of newly synthesized extracellular matrix. Nevertheless, the interactions between MSCs and collagen biomaterials are poorly known, and the strategies enhancing the extracellular matrix deposition are yet to be defined. In this study, we aim to investigate the fate of collagen when it is in contact with MSCs and hypothesize that protease inhibition will enhance their extracellular deposition of collagen fibrils. Specifically, human MSCs (hMSCs) were exposed to fluorescence-labeled collagen with and without intracellular or extracellular protease inhibitors (or both) before tracing the collagen at both intracellular and extracellular spaces. Collagen were internalized by hMSCs and degraded intracellularly in lysosomes. In the presence of protease inhibitors, both intracellular collagen fibril growth and extracellular deposition of collagen fibrils were enhanced. Moreover, protease inhibitors work synergistically with ascorbic acid, a well-known matrix deposition-enhancing reagent, in further enhancing collagen fibril deposition at the extracellular space. These findings provide a better understanding of the interactions between hMSCs and collagen biomaterials and suggest a method to manipulate matrix remodeling and deposition of hMSCs, contributing to better scaffolding for tissue engineering and regenerative medicine.

  3. Dose of radiation enhancement, using silver nanoparticles in a human tissue equivalent gel dosimeter.

    Science.gov (United States)

    Hassan, Muhammad; Waheed, Muhammad Mohsin; Anjum, Muhammad Naeem

    2016-01-01

    To quantify the radiation dose enhancement in a human tissue-equivalent polymer gel impregnated with silver nanoparticles. The case-control study was conducted at the Bahawalpur Institute of Nuclear Medicine and Oncology, Bahawalpur, Pakistan, in January 2014. Silver nanoparticles used in this study were prepared by wet chemical method. Polymer gel was prepared by known quantity of gelatine, methacrylic acid, ascorbic acid, copper sulphate pentahydrate, hydroquinone and water. Different concentrations of silver nanoparticles were added to the gel during its cooling process. The gel was cooled in six plastic vials of 50ml each. Two vials were used as a control sample while four vials were impregnated with silver nanoparticles. After 22 hours, the vials were irradiated with gamma rays by aCobalt-60 unit. Radiation enhancement was assessed by taking magnetic resonance images of the vials. The images were analysed using Image J software. The dose enhancement factor was 24.17% and 40.49% for 5Gy and 10Gy dose respectively. The dose enhancement factor for the gel impregnated with 0.10mM silver nanoparticles was 32.88% and 51.98% for 5Gy and 10Gy dose respectively. The impregnation of a tissue-equivalent gel with silver nanoparticles resulted in dose enhancement and this effect was magnified up to a certain level with the increase in concentration of silver nanoparticles.

  4. Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells cultured in vitro.

    Science.gov (United States)

    Tóth, F D; Mosborg-Petersen, P; Kiss, J; Aboagye-Mathiesen, G; Zdravkovic, M; Hager, H; Aranyosi, J; Lampé, L; Ebbesen, P

    1994-06-01

    We examined if Fc receptor-mediated antibody-dependent enhancement (FcR-ADE) or complement-mediated antibody-dependent enhancement (C'-ADE) of virus infection can contribute to increasing replication of HIV-1 in human syncytiotrophoblast (ST) cells. Here we report that both FcR-ADE and C'-ADE may result in enhanced virus release from HIV-1-infected ST cells. We show that FcR-ADE of HIV-1 infection in ST cells is mediated by FcRIII and other FcR(s) belonging to undetermined Fc classes and does not require CD4 receptors, whereas C'-ADE uses both CD4 and CR2-like receptors. FcR-ADE seems to be more efficient in enhancing HIV-1 replication than C'-ADE. While FcR-ADE leads to increased internalization of HIV-1, C'-ADE does not result in enhanced endocytosis of the virus. In addition, antibodies mediating FcR-ADE are reactive with the gp120 viral envelope antigen, whereas antibodies involved in C'-ADE react with the viral transmembrane glycoprotein gp41. Data suggest that both FcR-ADE and C'-ADE may contribute to the spread of HIV-1 from mother to the fetus.

  5. Gold nanoparticles in injectable calcium phosphate cement enhance osteogenic differentiation of human dental pulp stem cells.

    Science.gov (United States)

    Xia, Yang; Chen, Huimin; Zhang, Feimin; Bao, Chongyun; Weir, Michael D; Reynolds, Mark A; Ma, Junqing; Gu, Ning; Xu, Hockin H K

    2018-01-01

    In this study, a novel calcium phosphate cement containing gold nanoparticles (GNP-CPC) was developed. Its osteogenic induction ability on human dental pulp stem cells (hDPSCs) was investigated for the first time. The incorporation of GNPs improved hDPSCs behavior on CPC, including better cell adhesion (about 2-fold increase in cell spreading) and proliferation, and enhanced osteogenic differentiation (about 2-3-fold increase at 14 days). GNPs endow CPC with micro-nano-structure, thus improving surface properties for cell adhesion and subsequent behaviors. In addition, GNPs released from GNP-CPC were internalized by hDPSCs, as verified by transmission electron microscopy (TEM), thus enhancing cell functions. The culture media containing GNPs enhanced the cellular activities of hDPSCs. This result was consistent with and supported the osteogenic induction results of GNP-CPC. In conclusion, GNP-CPC significantly enhanced the osteogenic functions of hDPSCs. GNPs are promising to modify CPC with nanotopography and work as bioactive additives thus enhance bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Revealing Hearts

    DEFF Research Database (Denmark)

    Saghaug, Kristin Falck; Pattison, George; Lindgren, Peter

    2014-01-01

    with reference to Tillich’s account of the meaning of revelation through culture and art, summed up in the statement that “(...) revelation is the manifestation of the ground of being for human knowledge” (Tillich, 1951, p.94), which, we argue, can be extended to everyday experiences, for example, in business......Some small business owners want to balance personal values as well as economic values. “I have to follow my heart” or “it must be meaningful” some of them say. But how might they be able to know what gives meaning to the heart? The philosophical theologian Paul Tillich finds that the problem...... life. In Tillich’s own terms, even preliminary concerns may point at an ultimate concern (Tillich, 1964), which can also be understood as ‘knowledge of the heart’. Our account is also connected to wider discussions concerning the nature of intuition....

  7. Combination of Vaccine-Strain Measles and Mumps Viruses Enhances Oncolytic Activity against Human Solid Malignancies.

    Science.gov (United States)

    Son, Ho Anh; Zhang, LiFeng; Cuong, Bui Khac; Van Tong, Hoang; Cuong, Le Duy; Hang, Ngo Thu; Nhung, Hoang Thi My; Yamamoto, Naoki; Toan, Nguyen Linh

    2018-02-07

    Oncolytic measles and mumps viruses (MeV, MuV) have a potential for anti-cancer treatment. We examined the anti-tumor activity of MeV, MuV, and MeV-MuV combination (MM) against human solid malignancies (HSM). MeV, MuV, and MM targeted and significantly killed various cancer cell lines of HSM but not normal cells. MM demonstrated a greater anti-tumor effect and prolonged survival in a human prostate cancer xenograft tumor model compared to MeV and MuV. MeV, MuV, and MM significantly induced the expression of immunogenic cell death markers and enhanced spleen-infiltrating immune cells. In conclusion, MM combination significantly improves the treatment of human solid malignancies.

  8. Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution.

    Science.gov (United States)

    Medina-Carmona, Encarnación; Fuchs, Julian E; Gavira, Jose A; Mesa-Torres, Noel; Neira, Jose L; Salido, Eduardo; Palomino-Morales, Rogelio; Burgos, Miguel; Timson, David J; Pey, Angel L

    2017-09-15

    Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please

  9. Supportive Accountability: A Model for Providing Human Support to Enhance Adherence to eHealth Interventions

    Science.gov (United States)

    2011-01-01

    The effectiveness of and adherence to eHealth interventions is enhanced by human support. However, human support has largely not been manualized and has usually not been guided by clear models. The objective of this paper is to develop a clear theoretical model, based on relevant empirical literature, that can guide research into human support components of eHealth interventions. A review of the literature revealed little relevant information from clinical sciences. Applicable literature was drawn primarily from organizational psychology, motivation theory, and computer-mediated communication (CMC) research. We have developed a model, referred to as “Supportive Accountability.” We argue that human support increases adherence through accountability to a coach who is seen as trustworthy, benevolent, and having expertise. Accountability should involve clear, process-oriented expectations that the patient is involved in determining. Reciprocity in the relationship, through which the patient derives clear benefits, should be explicit. The effect of accountability may be moderated by patient motivation. The more intrinsically motivated patients are, the less support they likely require. The process of support is also mediated by the communications medium (eg, telephone, instant messaging, email). Different communications media each have their own potential benefits and disadvantages. We discuss the specific components of accountability, motivation, and CMC medium in detail. The proposed model is a first step toward understanding how human support enhances adherence to eHealth interventions. Each component of the proposed model is a testable hypothesis. As we develop viable human support models, these should be manualized to facilitate dissemination. PMID:21393123

  10. How the unique configuration of the human head may enhance flavor perception capabilities: an evolutionary perspective

    Directory of Open Access Journals (Sweden)

    Daniel E Lieberman

    2014-07-01

    Full Text Available Since flavor derives from the synthesis of taste, somatosensation and smell, one of the most important factors in the ability to perceive flavor is retronasal olfaction in which volatile compounds pass from the oral cavity through the pharynx to the olfactory epithelium. Retronasal olfaction has been documented in both humans and rodents, but appears less effective in rodents than orthonasal olfaction because expired air does not come into as much contact with the sensory neurons in the olfactory epithelium as inspired air [1,2]. Detailed comparisons of retronasal airflow patterns among different species have not been conducted, but several lines of evidence lead to the hypothesis that retronasal airflow may be specially enhanced in humans because of four derived features of the human head and neck that evolved at different stages because of selection for functions other than olfaction [3]. If so, then human flavor perception capabilities may be more derived than is commonly appreciated, and perhaps played a role in selecting for the evolution of cooking. The first derived adaptation that aids human retronasal olfaction is the absence of the transverse lamina, a horizontal shelf of bone that partitions the olfactory chamber of the nasal fossa from the more inferior respiratory passage. This lamina, which is present in most mammals, was lost during the evolution of monkeys (haplorhines from more primitive primates (strepsirhines as part of a reorganization of the nasal cavity. The function of the transverse lamina has not been tested but it probably aids orthonasal olfaction by trapping inspired air in the olfactory region. Loss of the transverse lamina is commonly interpreted to be one of several trade-offs in primate evolution that favored vision over olfaction [4], but it likely benefits retronasal olfaction by permitting a direct pathway for expired air to flow towards the olfactory epithelium. A second derived adaptation present in humans is

  11. In-plant application of industry experience to enhance human reliability

    International Nuclear Information System (INIS)

    Hannaman, G.W.; Singh, A.

    1993-01-01

    This paper describes the way that modern data-base computer tools can enhance the ability to collect, organize, evaluate, and use industry experience. By combining the computer tools with knowledge from human reliability assessment tools, data, and frameworks, the data base can become a tool for collecting and assessing the lessons learned from past events. By integrating the data-base system with plant risk models, engineers can focus on those activities that can enhance over-all system reliability. The evaluation helps identify technology and tools to reduce human errors during operations and maintenance. Learning from both in-plant and industry experience can help enhance safety and reduce the cost of plant operations. Utility engineers currently assess events that occur in nuclear plants throughout the world for in-plant applicability. Established computer information networks, documents, bulletins, and other information sources provide a large number of event descriptions to help individual plants benefit from this industry experience. The activities for coordinating reviews of event descriptions from other plants for in-plant applications require substantial engineering time to collect, organize, evaluate, and apply. Data-base tools can help engineers efficiently handle and sort the data so that they can concentrate on understanding the importance of the event, developing cost-effective interventions, and communicating implementation plans for plant improvement. An Electric Power Research Institute human reliability project has developed a classification system with modern data-base software to help engineers efficiently process, assess, and apply information contained in the events to enhance plant operation. Plant-specific classification of industry experience provides a practical method for efficiently taking into account industry when planning maintenance activities and reviewing plant safety

  12. Overexpression of FABP3 inhibits human bone marrow derived mesenchymal stem cell proliferation but enhances their survival in hypoxia

    International Nuclear Information System (INIS)

    Wang, Suna; Zhou, Yifu; Andreyev, Oleg; Hoyt, Robert F.; Singh, Avneesh; Hunt, Timothy; Horvath, Keith A.

    2014-01-01

    Studying the proliferative ability of human bone marrow derived mesenchymal stem cells in hypoxic conditions can help us achieve the effective regeneration of ischemic injured myocardium. Cardiac-type fatty acid binding protein (FABP3) is a specific biomarker of muscle and heart tissue injury. This protein is purported to be involved in early myocardial development, adult myocardial tissue repair and responsible for the modulation of cell growth and proliferation. We have investigated the role of FABP3 in human bone marrow derived mesenchymal stem cells under ischemic conditions. MSCs from 12 donors were cultured either in standard normoxic or modified hypoxic conditions, and the differential expression of FABP3 was tested by quantitative RT PCR and western blot. We also established stable FABP3 expression in MSCs and searched for variation in cellular proliferation and differentiation bioprocesses affected by hypoxic conditions. We identified: (1) the FABP3 differential expression pattern in the MSCs under hypoxic conditions; (2) over-expression of FABP3 inhibited the growth and proliferation of the MSCs; however, improved their survival in low oxygen environments; (3) the cell growth factors and positive cell cycle regulation genes, such as PCNA, APC, CCNB1, CCNB2 and CDC6 were all down-regulated; while the key negative cell cycle regulation genes TP53, BRCA1, CASP3 and CDKN1A were significantly up-regulated in the cells with FABP3 overexpression. Our data suggested that FABP3 was up-regulated under hypoxia; also negatively regulated the cell metabolic process and the mitotic cell cycle. Overexpression of FABP3 inhibited cell growth and proliferation via negative regulation of the cell cycle and down-regulation of cell growth factors, but enhances cell survival in hypoxic or ischemic conditions. - Highlights: • FABP3 expression pattern was studied in 12 human hypoxic-MSCs. • FABP3 mRNA and proteins are upregulated in the MSCs under hypoxic conditions.

  13. Creation of an in vitro microenvironment to enhance human fetal synovium-derived stem cell chondrogenesis.

    Science.gov (United States)

    Li, Jingting; He, Fan; Pei, Ming

    2011-09-01

    Our aim was to assess the feasibility of the sequential application of extracellular matrix (ECM) and low oxygen to enhance chondrogenesis in human fetal synovium-derived stem cells (hfSDSCs). Human fetal synovial fibroblasts (hfSFs) were characterized and found to include hfSDSCs, as evidenced by their multi-differentiation capacity and the surface phenotype markers typical of mesenchymal stem cells. Passage-7 hfSFs were plated on either conventional plastic flasks (P) or ECM deposited by hfSFs (E) for one passage. Passage-8 hfSFs were then reseeded for an additional passage on either P or E. The pellets from expanded hfSFs were incubated in a serum-free chondrogenic medium supplemented with 10 ng/ml transforming growth factor-β3 under either normoxia (21% O(2); 21) or hypoxia (5% O(2); 5) for 14 days. Pellets were collected for evaluation of the treatments (EE21, EE5, EP21, EP5, PE21, PE5, PP21, and PP5) on expanded hfSF chondrogenesis by using histology, immunostaining, biochemistry, and real-time polymerase chain reaction. Our data suggest that, compared with seeding on conventional plastic flasks, hfSFs expanded on ECM exhibit a lower expression of senescence-associated β-galactosidase and an enhanced level of stage-specific embryonic antigen-4. ECM-expanded hfSFs also show increased cell numbers and an enhanced chondrogenic potential. Low oxygen (5% O(2)) during pellet culture enhances hfSF chondrogenesis. Thus, we demonstrate, for the first time, the presence of stem cells in hfSFs, and that modulation of the in vitro microenvironment can enhance hfSDSC chondrogenesis. hfSDSCs might represent a promising cell source for cartilage tissue engineering and regeneration.

  14. Enhancement of P53-Mutant Human Colorectal Cancer Cells Radiosensitivity by Flavonoid Fisetin

    International Nuclear Information System (INIS)

    Chen Wenshu; Lee Yijang; Yu Yichu; Hsaio Chinghui

    2010-01-01

    Purpose: The aim of this study was to investigate whether fisetin is a potential radiosensitizer for human colorectal cancer cells, which are relatively resistant to radiotherapy. Methods and Materials: Cell survival was examined by clonogenic survival assay, and DNA fragmentation was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The effects of treatments on cell cycle distribution and apoptosis were examined by flow cytometry. Western blot analysis was performed to ascertain the protein levels of γ-H2AX, phospho-Chk2, active caspase-3, PARP cleavage, phospho-p38, phospho-AKT, and phospho-ERK1/2. Results: Fisetin pretreatment enhanced the radiosensitivity of p53-mutant HT-29 human colorectal cancer cells but not human keratocyte HaCaT cells; it also prolonged radiation-induced G 2 /M arrest, enhanced radiation-induced cell growth arrest in HT-29 cells, and suppressed radiation-induced phospho-H2AX (Ser-139) and phospho-Chk2 (Thr-68) in p53-mutant HT-29 cells. Pretreatment with fisetin enhanced radiation-induced caspase-dependent apoptosis in HT-29 cells. Fisetin pretreatment augmented radiation-induced phosphorylation of p38 mitogen-activated protein kinase, which is involved in caspase-mediated apoptosis, and SB202190 significantly reduced apoptosis and radiosensitivity in fisetin-pretreated HT-29 cells. By contrast, both phospho-AKT and phospho-ERK1/2, which are involved in cell proliferation and antiapoptotic pathways, were suppressed after irradiation combined with fisetin pretreatment. Conclusions: To our knowledge, this study is the first to provide evidence that fisetin exerts a radiosensitizing effect in p53-mutant HT-29 cells. Fisetin could potentially be developed as a novel radiosensitizer against radioresistant human cancer cells.

  15. Heart Truth

    Science.gov (United States)

    ... health! Get a free badge or banner to post to your website or blog. Are you at risk for heart disease? Here's how to find out . Planning to use The Heart Truth logo? Check out our logo guidelines and downloads. ...

  16. Heart Disease

    Science.gov (United States)

    ... it may be caused by diseases, such as connective tissue disorders, excessive iron buildup in your body (hemochromatosis), the buildup of abnormal proteins (amyloidosis) or by some cancer treatments. Causes of heart infection A heart infection, ...

  17. Heart Attack

    Science.gov (United States)

    ... family history of heart attack race – African Americans, Mexican Americans, Native Americans, and native Hawaiians are at ... Your doctor will prescribe the medicines that are right for you. If you have had a heart ...

  18. Heart pacemaker

    Science.gov (United States)

    Cardiac pacemaker implantation; Artificial pacemaker; Permanent pacemaker; Internal pacemaker; Cardiac resynchronization therapy; CRT; Biventricular pacemaker; Arrhythmia - pacemaker; Abnormal heart ...

  19. The use of cell-sheet technique eliminates arrhythmogenicity of skeletal myoblast-based therapy to the heart with enhanced therapeutic effects.

    Science.gov (United States)

    Narita, Takuya; Shintani, Yasunori; Ikebe, Chiho; Kaneko, Masahiro; Harada, Narumi; Tshuma, Nomathamsanqa; Takahashi, Kunihiko; Campbell, Niall G; Coppen, Steven R; Yashiro, Kenta; Sawa, Yoshiki; Suzuki, Ken

    2013-09-20

    Clinical application of skeletal myoblast transplantation has been curtailed due to arrhythmogenicity and inconsistent therapeutic benefits observed in previous studies. However, these issues may be solved by the use of a new cell-delivery mode. It is now possible to generate "cell-sheets" using temperature-responsive dishes without artificial scaffolds. This study aimed to validate the safety and efficacy of epicardial placement of myoblast-sheets (myoblast-sheet therapy) in treating heart failure. After coronary artery ligation in rats, the same numbers of syngeneic myoblasts were transplanted by intramyocardial injection or cell-sheet placement. Continuous radio-telemetry monitoring detected increased ventricular arrhythmias, including ventricular tachycardia, after intramyocardial injection compared to the sham-control, while these were abolished in myoblast-sheet therapy. This effect was conjunct with avoidance of islet-like cell-cluster formation that disrupts electrical conduction, and with prevention of increased arrhythmogenic substrates due to exaggerated inflammation. Persistent ectopic donor cells were found in the lung only after intramyocardial injection, strengthening the improved safety of myoblast-sheet therapy. In addition, myoblast-sheet therapy enhanced cardiac function, corresponding to a 9.2-fold increase in donor cell survival, compared to intramyocardial injection. Both methods achieved reduced infarct size, decreased fibrosis, attenuated cardiomyocyte hypertrophy, and increased neovascular formation, in association with myocardial upregulation of a group of relevant molecules. The pattern of these beneficial changes was similar between two methods, but the degree was more substantial after myoblast-sheet therapy. The cell-sheet technique enhanced safety and therapeutic efficacy of myoblast-based therapy, compared to the current method, thereby paving the way for clinical application. Copyright © 2012 Elsevier Ireland Ltd. All rights

  20. Abbreviated Resonant Frequency Training to Augment Heart Rate Variability and Enhance On-Demand Emotional Regulation in Elite Sport Support Staff.

    Science.gov (United States)

    Gross, Mike J; Shearer, David A; Bringer, Joy D; Hall, Ross; Cook, Christian J; Kilduff, Liam P

    2016-09-01

    Support and management staff in elite sport experience work-related stress and emotional disturbance to a similar extent as athletes (Fletcher and Wagstaff 2009). The resonant frequency breathing technique (Lehrer et al. 2000) can inhibit autonomic changes associated with stressful situations or events and as such provides a potential emotional regulation tool. The present study utilised five practitioner-led heart rate variability (HRV) biofeedback sessions and home practice via mobile applications to train support and management staff (n = 9) in resonant frequency breathing techniques. Although baseline HRV did not change from pre to post training, participants increased total HRV (i.e., SDNN; p = .006), parasympathetic HRV (i.e., RMSSD; p = .028) and HRV reflective of baroreflex function (i.e., low frequency power; p = .018) while accurately performing resonant frequency breathing without a breath pacer. Post-intervention questionnaire data revealed an increase (p = .032) in habitual use of somatic strategies for emotional regulation, and social validation data suggested that the technique enhanced emotional regulation at home, work and during international competition. HRV biofeedback and the resonant frequency technique provided an on-demand emotional regulation technique for elite sport support and management staff.

  1. The role of indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection

    International Nuclear Information System (INIS)

    De Nardo, D.; Scibilia, G.; Macchiarelli, A.G.

    1989-01-01

    The identification of rejection after heart transplantation in patients receiving cyclosporine immunosuppressive therapy requires the endomyocardial biopsy, an invasive method associated with a finite morbidity. To evaluate the role of indium-111 antimyosin (Fab) scintigraphy as a noninvasive surveillance method of heart transplant rejection, the Fab fragment of murine monoclonal antimyosin antibodies labeled with indium-111 was administered intravenously in 30 scintigraphic studies to 10 consecutive heart transplant recipients. Endomyocardial biopsy specimens were obtained 72 hours after each scintigraphic study. Nineteen scintigraphic studies had negative findings; no false negative finding was obtained. Eleven antimyosin scintigraphic studies had positive findings, and in these studies endomyocardial biopsy revealed mild rejection in two cases, moderate acute rejection with myocyte necrosis in two cases, myocyte necrosis as a consequence of ischemic injury in six cases, and possibly cytotoxic damage in one case. Antimyosin scintigraphy may represent a reliable screening method for the surveillance of heart transplant patients. In the presence of a negative finding from antimyosin scintigraphy, it may be possible to avoid endomyocardial biopsy. Conversely, in patients who have a positive finding from antimyosin scintigraphy, the endomyocardial biopsy is mandatory to establish the definitive diagnosis by histologic examination of the myocardium

  2. Effect of a single oral dose of milrinone on left ventricular diastolic performance in the failing human heart

    NARCIS (Netherlands)

    F. Piscione; B.E. Jaski; G.J. Wenting (Gert); P.W.J.C. Serruys (Patrick)

    1987-01-01

    textabstractIn 14 patients with severe congestive heart failure, left ventricular pressure (measured by tip manometer) and derived variables were measured before and every 10 minutes after administration of oral milrinone (10 mg) for 50 minutes along with measurements of coronary sinus blood flow

  3. Alloreactive lymphoid infiltrates in human heart transplants: Loss of class II-directed cytotoxicity more than 3 months after transplantation

    NARCIS (Netherlands)

    A.J. Ouwehand; L.M.B. Vaessen (Leonard); C.C. Baan (Carla); N.H.P.M. Jutte (Nicolet); A.H.M.M. Balk (Aggie); C.E. Essed; E. Bos (Egbert); F.H.J. Claas (Frans); W. Weimar (Willem)

    1991-01-01

    markdownabstractAbstract From 535 endomyocardial biopsies (87 heart transplant recipients) 283 cell cultures could be generated. All cultures tested contained T lymphocytes and in most cases CD4 was the predominant phenotype at any time posttransplant. A significantly higher proportion of

  4. Are adipose-derived stem cells cultivated in human platelet lysate suitable for heart valve tissue engineering?

    NARCIS (Netherlands)

    Frese, L.; Sasse, T.; Sanders, B.; Baaijens, F.P.T.; Beer, G.M.; Hoerstrup, S.P.

    2017-01-01

    Tissue-engineered heart valves represent a promising strategy for the growing need for valve replacements in cardiovascular medicine. Recent studies have shown that adipose-derived stem cells (ADSC) are a viable cell source, as they are readily available in both the young and the elderly, show

  5. Perioperative and postoperative course of cytokines and the metabolic activity of neutrophils in human cardiac operations and heart transplantation

    Czech Academy of Sciences Publication Activity Database

    Kubala, Lukáš; Číž, Milan; Vondráček, Jan; Černý, J.; Němec, P.; Studeník, P.; Čížová, Hana; Lojek, Antonín

    2002-01-01

    Roč. 124, č. 12 (2002), s. 1122-1129 ISSN 0022-5223 R&D Projects: GA ČR GA524/01/1219; GA ČR GA524/00/1223 Institutional research plan: CEZ:AV0Z5004920 Keywords : heart transplantation * cardiopulmonary bypass * inflammation Subject RIV: BO - Biophysics Impact factor: 2.842, year: 2002

  6. Plasma Amino Acid Abnormalities in Chronic Heart Failure. Mechanisms, Potential Risks and Targets in Human Myocardium Metabolism

    Directory of Open Access Journals (Sweden)

    Roberto Aquilani

    2017-11-01

    Full Text Available The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF, and relate them to left ventricular function and disease severity. Amino acids (AAs play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA class II to IV were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI, protein-, fat-, carbohydrate-intake, resting energy expenditure (REE, total daily energy expenditure (REE × 1.3, and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001 and cardiac index (r = 0.4243; p = 0.0028. The value of arterial aspartic acid (µmol/L multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076. All NYHA groups had adequate protein intake (≥1.1 g/kg/day and inadequate calorie intake (KcalI < REE × 1.3 was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.

  7. Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells.

    Science.gov (United States)

    Zeng, Wei; Xiao, Tao; Cai, Anlie; Cai, Weiliang; Liu, Huanhuan; Liu, Jingling; Li, Jie; Tan, Miduo; Xie, Li; Liu, Ying; Yang, Xiangcheng; Long, Yi

    2017-01-01

    Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy. We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy. These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

  8. Preoperative assessment of congestive liver dysfunction using technetium-99m galactosyl human Serum albumin liver scintigraphy in patients with severe valvular heart disease

    International Nuclear Information System (INIS)

    Nishi, Hiroyuki; Matsumiya, Goro; Takano, Hiroshi; Ichikawa, Hajime; Miyagawa, Shigeru; Sawa, Yoshiki; Takahashi, Toshiki

    2007-01-01

    Severe valvular heart disease is often complicated by congestive liver dysfunction, which greatly compromises the operative results. We evaluated congestive liver dysfunction by a novel approach using technetium-99m galactosyl human serum albumin ( 99m Tc-GSA) with liver scintigraphy. Between 1998 and 2004, we performed scintigraphy accompanied by 99m Tc-GSA in 28 patients who had valvular heart disease with moderate-to-severe tricuspid regurgitation and who showed symptoms of right heart failure. Based on the results, we calculated a receptor index (LHL15) and an index of blood clearance (HH15) and assessed the correlation between these factors and postoperative liver dysfunction, defined as the maximum serum total bilirubin level (max T-bil) as >2.0 mg/dl. Nineteen patients, including four who died in hospital, had postoperative liver dysfunction. The level of HH15 was significantly higher and the level of cholinesterase was significantly lower (P 99m Tc-GSA is a clinically useful predictor of postoperative liver dysfunction in patients with severe valvular disease. (author)

  9. Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.

    Science.gov (United States)

    Facer, Paul; Punjabi, Prakash P; Abrari, Andleeb; Kaba, Riyaz A; Severs, Nicholas J; Chambers, John; Kooner, Jaspal S; Anand, Praveen

    2011-01-01

    We have shown that the gene SCN10A encoding the sodium channel Na(v)1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na(v)1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Na(v)1.8 and other key nociceptive ion channels, including Na(v)1.7, Na(v)1.9, capsaicin receptor TRPV1, and purinergic receptor P2X(3), have not been reported in human heart. The aim of this study was to determine the distribution of Na(v)1.8, related sodium and other sensory channels in human cardiac tissue, and correlate their density with sympathetic nerves, regenerating nerves (GAP-43), and vascularity. Human heart atrial appendage tissues (n = 13) were collected during surgery for valve disease. Tissues were investigated by immunohistology using specific antibodies to Na(v)1.8 and other markers. Na(v)1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Na(v)1.8 nerve fibres per mm(2) correlated significantly with vascular markers. Na(v)1.8-immunoreactivity was present also in cardiomyocytes with a similar distribution pattern to that seen with connexins, the specialised gap junction proteins of myocardial intercalated discs. Na(v)1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Na(v)1.7, Na(v)1.9, TRPV1, P2X(3)/P2X(2), and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Na(v)1.8 is present in sensory nerves and cardiomyocytes of human heart. Na(v)1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.

  10. Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4.

    Science.gov (United States)

    Barhanpurkar-Naik, Amruta; Mhaske, Suhas T; Pote, Satish T; Singh, Kanupriya; Wani, Mohan R

    2017-07-14

    Mesenchymal stem cells (MSCs) represent an important source for cell therapy in regenerative medicine. MSCs have shown promising results for repair of damaged tissues in various degenerative diseases in animal models and also in human clinical trials. However, little is known about the factors that could enhance the migration and tissue-specific engraftment of exogenously infused MSCs for successful regenerative cell therapy. Previously, we have reported that interleukin-3 (IL-3) prevents bone and cartilage damage in animal models of rheumatoid arthritis and osteoarthritis. Also, IL-3 promotes the differentiation of human MSCs into functional osteoblasts and increases their in-vivo bone regenerative potential in immunocompromised mice. However, the role of IL-3 in migration of MSCs is not yet known. In the present study, we investigated the role of IL-3 in migration of human MSCs under both in-vitro and in-vivo conditions. MSCs isolated from human bone marrow, adipose and gingival tissues were used for in-vitro cell migration, motility and wound healing assays in the presence or absence of IL-3. The effect of IL-3 preconditioning on expression of chemokine receptors and integrins was examined by flow cytometry and real-time PCR. The in-vivo migration of IL-3-preconditioned MSCs was investigated using a subcutaneous matrigel-releasing stromal cell-derived factor-1 alpha (SDF-1α) model in immunocompromised mice. We observed that human MSCs isolated from all three sources express IL-3 receptor-α (IL-3Rα) both at gene and protein levels. IL-3 significantly enhances in-vitro migration, motility and wound healing abilities of MSCs. Moreover, IL-3 preconditioning upregulates expression of chemokine (C-X-C motif) receptor 4 (CXCR4) on MSCs, which leads to increased migration of cells towards SDF-1α. Furthermore, CXCR4 antagonist AMD3100 decreases the migration of IL-3-treated MSCs towards SDF-1α. Importantly, IL-3 also induces in-vivo migration of MSCs towards

  11. Task-dependent enhancement of facial expression and identity representations in human cortex.

    Science.gov (United States)

    Dobs, Katharina; Schultz, Johannes; Bülthoff, Isabelle; Gardner, Justin L

    2018-05-15

    What cortical mechanisms allow humans to easily discern the expression or identity of a face? Subjects detected changes in expression or identity of a stream of dynamic faces while we measured BOLD responses from topographically and functionally defined areas throughout the visual hierarchy. Responses in dorsal areas increased during the expression task, whereas responses in ventral areas increased during the identity task, consistent with previous studies. Similar to ventral areas, early visual areas showed increased activity during the identity task. If visual responses are weighted by perceptual mechanisms according to their magnitude, these increased responses would lead to improved attentional selection of the task-appropriate facial aspect. Alternatively, increased responses could be a signature of a sensitivity enhancement mechanism that improves representations of the attended facial aspect. Consistent with the latter sensitivity enhancement mechanism, attending to expression led to enhanced decoding of exemplars of expression both in early visual and dorsal areas relative to attending identity. Similarly, decoding identity exemplars when attending to identity was improved in dorsal and ventral areas. We conclude that attending to expression or identity of dynamic faces is associated with increased selectivity in representations consistent with sensitivity enhancement. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. 8-aminoadenosine enhances radiation-induced cell death in human lung carcinoma A549 cells

    International Nuclear Information System (INIS)

    Meike, Shunsuke; Yamamori, Tohru; Yasui, Hironobu; Eitaki, Masato; Inanami, Osamu; Matsuda, Akira

    2011-01-01

    The combination of a chemotherapeutic agent and radiation is widely applied to enhance cell death in solid tumor cells in cancer treatment. The purine analogue 8-aminoadenosine (8-NH 2 -Ado) is known to be a transcription inhibitor that has proved very effective in multiple myeloma cell lines and primary indolent leukemia cells. In this report, to examine whether 8-NH 2 -Ado had the ability to enhance the radiation-induced cell killing in solid tumor cells, human lung adenocarcinoma A549 cells were irradiated in the presence and absence of 8-NH 2 -Ado. 8-NH 2 -Ado significantly increased reproductive cell death and apoptosis in A549 cells exposed to X-rays. When peptide inhibitors against caspase-3, -8, and -9 were utilized to evaluate the involvement of caspases, all inhibitors suppressed the enhancement of radiation-induced apoptosis, suggesting that not only mitochondria-mediated apoptotic signal transduction pathways but also death receptor-mediated pathways were involved in this enhancement of apoptosis. In addition, in the cells exposed to the treatment combining X-irradiation and 8-NH 2 -Ado, reduction of the intracellular ATP concentration was essential for survival, and down-regulation of the expression of antiapoptotic proteins such as survivin and X-linked inhibitor of apoptosis protein (XIAP) was observed. These results indicate that 8-NH 2 -Ado has potential not only as an anti-tumor drug for leukemia and lymphoma but also as a radiosensitizing agent for solid tumors. (author)

  13. Vehicle and enhancer effects on human skin penetration of aminophylline from cream formulations: evaluation in vivo.

    Science.gov (United States)

    Wang, Lai-Hao; Wang, Chia-Chen; Kuo, Su-Ching

    2007-01-01

    The effects of four essential oils (rosemary, ylang, lilacin, and peppermint oils), and three plant oils (jojoba oil, corn germ oil, and olive oil) on the permeation of aminophylline were studied using human skin. The permeation effects of these oils were compared with those of three chemical penetration enhancers. Although all oils enhanced the permeation of aminophylline, their effects were less than that of ethanol. Jojoba oil was found to be the most active, causing about a 32% peak height decrease of N-H bending absorbances in comparison with the control, while peppermint, lilacin, rosemary, and ylang oils caused 28%, 24%, 18%, and 12% peak height decreases, respectively. Microemulsions containing 10% jojoba oil and 30% corn germ oil were found to be superior vehicles for the percutaneous absorption of aminophylline. Comparision with results obtained from high-performance liquid chromatography shows good agreement.

  14. Enhancing student perspectives of humanism in medicine: reflections from the Kalaupapa service learning project.

    Science.gov (United States)

    Lee, Winona K; Harris, Chessa C D; Mortensen, Kawika A; Long, Linsey M; Sugimoto-Matsuda, Jeanelle

    2016-05-09

    Service learning is endorsed by the Liaison Committee on Medical Education (LCME) as an integral part of U.S. medical school curricula for future physicians. Service learning has been shown to help physicians in training rediscover the altruistic reasons for pursuing medicine and has the potential to enhance students' perspectives of humanism in medicine. The Kalaupapa service learning project is a unique collaboration between disadvantaged post-baccalaureate students with an underserved rural community. This study was conducted to determine whether the Kalaupapa service learning curricula enhanced student perspectives of humanism in medicine at an early stage of their medical training. Program participants between 2008 and 2014 (n = 41) completed written reflections following the conclusion of the service learning project. Four prompts guided student responses. Reflections were thematically analyzed. Once all essays were read, team members compared their findings to condense or expand themes and assess levels of agreement. Emerging themes of resilience and unity were prominent throughout the student reflections. Students expressed respect and empathy for the patients' struggles and strengths, as well as those of their peers. The experience also reinforced students' commitment to service, particularly to populations in rural and underserved communities. Students also gained a deeper understanding of the patient experience and also of themselves as future physicians. To identify and address underserved and rural patients' health care needs, training programs must prepare an altruistic health care workforce that embraces the humanistic element of medicine. The Kalaupapa service learning project is a potential curricular model that can be used to enhance students' awareness and perspectives of humanism in medicine.

  15. The Arctic Alzheimer mutation enhances sensitivity to toxic stress in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Sennvik, Kristina; Nilsberth, Camilla; Stenh, Charlotte

    2002-01-01

    The E693G (Arctic) mutation of the amyloid precursor protein was recently found to lead to early-onset Alzheimer's disease in a Swedish family. In the present study, we report that the Arctic mutation decreases cell viability in human neuroblastoma cells. The cell viability, as measured by the MTT...... their secretion of beta-secretase cleaved amyloid precursor protein. The enhanced sensitivity to toxic stress in cells with the Arctic mutation most likely contributes to the pathogenic pathway leading to Alzheimer's disease....

  16. Enhancement of bone formation in rabbits by recombinant human growth hormone

    International Nuclear Information System (INIS)

    Ehrnberg, A.; Brosjoe, O.; Laaftman, P.; Nilsson, O.; Stroemberg, L.

    1993-01-01

    We studied the effect of human recombinant growth hormone on diaphyseal bone in 40 adult rabbits. The diaphyseal periosteum of one femur in each animal was mechanically stimulated by a nylon cerclage band. The bands induced an increase in bone formation, bone mineral content, and maximum torque capacity of the diaphyseal bone at 1 and 2 months. Growth hormone enhanced the anabolic effect of the cerclage bands on bone metabolism, evidenced by a further increase in torsional strength of the femurs. (au) (32 refs.)

  17. Glucose enhancement of human memory: a comprehensive research review of the glucose memory facilitation effect.

    Science.gov (United States)

    Smith, Michael A; Riby, Leigh M; Eekelen, J Anke M van; Foster, Jonathan K

    2011-01-01

    The brain relies upon glucose as its primary fuel. In recent years, a rich literature has developed from both human and animal studies indicating that increases in circulating blood glucose can facilitate cognitive functioning. This phenomenon has been termed the 'glucose memory facilitation effect'. The purpose of this review is to discuss a number of salient studies which have investigated the influence of glucose ingestion on neurocognitive performance in individuals with (a) compromised neurocognitive capacity, as well as (b) normally functioning individuals (with a focus on research conducted with human participants). The proposed neurocognitive mechanisms purported to underlie the modulatory effect of glucose on neurocognitive performance will also be considered. Many theories have focussed upon the hippocampus, given that this brain region is heavily implicated in learning and memory. Further, it will be suggested that glucose is a possible mechanism underlying the phenomenon that enhanced memory performance is typically observed for emotionally laden stimuli. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Human endothelin subtype A receptor enhancement during tissue culture via de novo transcription

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Nordström, Carl-Henrik; Edvinsson, Lars

    2002-01-01

    OBJECTIVE: Endothelin (ET) has, since its discovery, increasingly been considered a key player in the pathophysiological processes of cerebral vasospasm in the course of subarachnoid hemorrhage, although it remains unclear how ET is involved. We present data that indicate an inherent capacity...... of human cerebral arteries to change their sensitivity to ET. METHODS: Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into segments and subjected to organ culture for 48 hours. The vessels were then examined by using in vitro...... pharmacological methods and molecular biological techniques. RESULTS: After organ culture of the cerebral arteries, both the sensitivity to and potency of ET were enhanced (maximal response, 152 +/- 9%; -log (50% effective concentration), 10.3 +/- 0.3), in comparison with data for fresh cerebral arteries...

  19. Demineralized bone matrix and human cancellous bone enhance fixation of titanium implants

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Overgaard, Søren

    Best Poster 5Demineralized bone matrix and human cancellous bone enhance fixation of titanium implants AuthorsBabiker , H.; Ding M.; Overgaard S.InstitutionOrthopaedic Research Laboratory, Department of Orthopaedic Surgery, Odense University Hospital, Clinical Institute, University of Southern...... from human tissue were included (IsoTis OrthoBiologics, Inc. USA). Both materials are commercially available. Titanium alloy implants (Biomet Inc.) of 10 mm in length and 10 mm in diameter were inserted bilaterally into the femoral condyles of 8 skeletally mature sheep. Thus four implants...... with a concentric gap of 2 mm were implanted in each sheep. The gap was filled with: DBM; DBM/CB with ratio of 1/3; DBM/allograft with ratio of 1/3; or allograft (Gold standard), respectively. Standardised surgical procedure was used1. At sacrifice, 6 weeks after surgery, both distal femurs were harvested...

  20. Enhanced Contaminated Human Remains Pouch: initial development and preliminary performance assessments

    Energy Technology Data Exchange (ETDEWEB)

    Iseli, A.M.; Kwen, H.D.; Ul-Alam, M.; Balasubramanian, M.; Rajagopalan, S.

    2011-11-07

    The objective is to produce a proof of concept prototype Enhanced Contaminated Human Remains Pouch (ECHRP) with self-decontamination capability to provide increased protection to emergency response personnel. The key objective was to decrease the concentration of toxic chemicals through the use of an absorbent and reactive nanocellulose liner. Additionally, nanomaterials with biocidal properties were developed and tested as a 'stand-alone' treatment. The setting was a private company research laboratory. The main outcome measures were production of a functional prototype. A functional prototype capable of mitigating the threats due to sulfur mustard, Soman, and a large variety of liquid and vapor toxic industrial chemicals was produced. Stand-alone biocidal treatment efficacy was validated. The ECHRP provides superior protection from both chemical and biological hazards to various emergency response personnel and human remains handlers.

  1. Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development

    Directory of Open Access Journals (Sweden)

    Samuel Sances

    2018-04-01

    Full Text Available Summary: Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BMECs share common signaling pathways with neurons early in development, but their contribution to human neuronal maturation is largely unknown. To study this interaction and influence of microculture, we derived both spinal motor neurons and BMECs from human induced pluripotent stem cells and observed increased calcium transient function and Chip-specific gene expression in Organ-Chips compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular-neural interaction and specific gene activation that further enhanced neuronal function and in vivo-like signatures. The results show that the vascular system has specific maturation effects on spinal cord neural tissue, and the use of Organ-Chips can move stem cell models closer to an in vivo condition. : Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development. Keywords: organ-on-chip, spinal cord, iPSC, disease modeling, amyotrophic lateral sclerosis, microphysiological system, brain microvascular endothelial cells, spinal motor neurons, vasculature, microfluidic device

  2. Calcium phosphate thin films enhance the response of human mesenchymal stem cells to nanostructured titanium surfaces

    Directory of Open Access Journals (Sweden)

    Mura M McCafferty

    2014-05-01

    Full Text Available The development of biomaterial surfaces possessing the topographical cues that can promote mesenchymal stem cell recruitment and, in particular, those capable of subsequently directing osteogenic differentiation is of increasing importance for the advancement of tissue engineering. While it is accepted that it is the interaction with specific nanoscale topography that induces mesenchymal stem cell differentiation, the potential for an attendant bioactive chemistry working in tandem with such nanoscale features to enhance this effect has not been considered to any great extent. This article presents a study of mesenchymal stem cell response to conformal bioactive calcium phosphate thin films sputter deposited onto a polycrystalline titanium nanostructured surface with proven capability to directly induce osteogenic differentiation in human bone marrow–derived mesenchymal stem cells. The sputter deposited surfaces supported high levels of human bone marrow–derived mesenchymal stem cell adherence and proliferation, as determined by DNA quantification. Furthermore, they were also found to be capable of directly promoting significant levels of osteogenic differentiation. Specifically, alkaline phosphatase activity, gene expression and immunocytochemical localisation of key osteogenic markers revealed that the nanostructured titanium surfaces and the bioactive calcium phosphate coatings could direct the differentiation towards an osteogenic lineage. Moreover, the addition of the calcium phosphate chemistry to the topographical profile of the titanium was found to induce increased human bone marrow–derived mesenchymal stem cell differentiation compared to that observed for either the titanium or calcium phosphate coating without an underlying nanostructure. Hence, the results presented here highlight that a clear benefit can be achieved from a surface engineering strategy that combines a defined surface topography with an attendant, conformal

  3. Physiological Mechanisms Mediating the Coupling between Heart Period and Arterial Pressure in Response to Postural Changes in Humans

    OpenAIRE

    Silvani, Alessandro; Calandra-Buonaura, Giovanna; Johnson, Blair D.; van Helmond, Noud; Barletta, Giorgio; Cecere, Anna G.; Joyner, Michael J.; Cortelli, Pietro

    2017-01-01

    The upright posture strengthens the coupling between heart period (HP) and systolic arterial pressure (SAP) consistently with a greater contribution of the arterial baroreflex to cardiac control, while paradoxically decreasing cardiac baroreflex sensitivity (cBRS). To investigate the physiological mechanisms that mediate the coupling between HP and SAP in response to different postures, we analyzed the cross-correlation functions between low-frequency HP and SAP fluctuations and estimated cBR...

  4. A broader consideration of human factor to enhance sustainable building design.

    Science.gov (United States)

    Attaianese, Erminia

    2012-01-01

    The link between ergonomic/human factor and sustainability seems to be clearly evidenced mainly in relation to social dimension of sustainability, in order to contribute to assure corporate social responsibility and global value creation. But the will to establish an equilibrated connection among used resources in human activities, supported by the sustainability perspective, evidences that the contribution of ergonomics/human factors can be effectively enlarged to other aspects, especially in relation to building design. In fact a sustainable building is meant to be a building that contributes, through its characteristics and attribute, to a sustainable development by assuring, in the same time, a decrease of resources use and environmental impact and an increase of health, safety and comfort of the occupants. The purpose of this paper is to analyze in a broader sense the contribution of ergonomic/human factor to design of sustainable building, focusing how ergonomics principles, methodology and techniques can improve building design, enhancing its sustainability performance during all phases of building lifecycle.

  5. Enhancing Human Capital Development and Service Delivery in Nigerian Tertiary Institutions through Effective Academic Staff

    Directory of Open Access Journals (Sweden)

    Chinyeaka Igbokwe-Ibeto

    2014-09-01

    Full Text Available Within the framework of bureaucratic and human capital theories, an eclectic approach, the study examines the nexus between academic staff recruitment in Nigerian tertiary institutions and human capital development as well as service delivery with specific reference to universities. It is generally agreed that higher education is a sine-qua-non for human capital development and efficient service delivery. Higher education is a prerequisite for the production of highly competent experts, which in turn, contributes to the development of organizations and the economy at large. For these to be achieved, the right content and academic staff  must be in place to perform this varied function.  However, over the years the quality of human capital coming out of Nigerian universities and its impact on service delivery has become a source of concern to employers of labour and all stakeholders. Inferential opinions have traced the problem to the recruitment of incompetent academic staff. To investigate the issues raised, the study relied heavily on primary and secondary data and multi stage sampling was used to select the sample population. The data collected was presented in pie chart and simple percentage. Similarly, in order to test the hypotheses and establish the degree of dependence or independence of the variables under investigation, the chi-square statistical technique was used. The findings of the study revealed among others, that Nigerian universities do not employ merit, qualification and competency in the academic staff recruitment. It also established that there is a significant relationship between merit, qualification and competency based academic staff recruitment and human capital development and service delivery. To enhance human capital development and service delivery in Nigerian universities, the study recommends among others, that an independent body like the National University Commission (NUC should be given the responsibility of

  6. Generation of human iPSC line from a patient with laterality defects and associated congenital heart anomalies carrying a DAND5 missense alteration

    Directory of Open Access Journals (Sweden)

    Fernando Cristo

    2017-12-01

    Full Text Available A human iPSC line was generated from exfoliated renal epithelial (ERE cells of a patient affected with Congenital Heart Disease (CHD and Laterality Defects carrying tshe variant p.R152H in the DAND5 gene. The transgene-free iPSCs were generated with the human OSKM transcription factor using the Sendai-virus reprogramming system. The established iPSC line had the specific heterozygous alteration, a stable karyotype, expressed pluripotency markers and generated embryoid bodies that can differentiate towards the three germ layers in vitro. This iPSC line offers a useful resource to study the molecular mechanisms of cardiomyocyte proliferation, as well as for drug testing.

  7. Conscious and unconscious sensory inflows allow effective control of the functions of the human brain and heart at the initial ageing stage.

    Science.gov (United States)

    Bykov, Anatolij T; Malyarenko, Tatyana N; Malyarenko, Yurij E; Terentjev, Vladimir P; Dyuzhikov, Alexandr A

    2006-11-01

    The authors of the present article based their assumption on the concept that the sensory systems are the "windows to the brain" through which various functions of the human organism can be controlled. Comprehension of the fundamental mechanisms of the optimization of the sensory systems, brain, and cardiac functions has increased based on the prolonged sensory flows using conscious and unconscious aromatherapy and multimodal sensory activation. Sensory flow evoked stable systemic responses, including adaptive alteration of psycho-emotional state, attention, memory, sensorimotor reactions, intersensory interaction, visual information processing, statokinetic stability, and autonomic heart rhythm control. The efficacy and expediency of the use of sensory flow for non-medicinal correction of vital functions of the human organism at the initial stages of ageing was revealed.

  8. Endoplasmic Reticulum Stress Sensor IRE1α Enhances IL-23 Expression by Human Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Saioa Márquez

    2017-06-01

    Full Text Available Human monocyte-derived dendritic cells (DCs exposed to pathogen-associated molecular patterns (PAMPs undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER stress response. Indeed, stimulation of DCs with PAMPs in the presence of 2-DG robustly activated inositol-requiring protein 1α (IRE1α signaling and to a lesser extent the PERK arm of the unfolded protein response. Additional ER stressors such as tunicamycin and thapsigargin also promoted IL-23 expression by PAMP-stimulated DCs. Pharmacological, biochemical, and genetic analyses using conditional knockout mice revealed that IL-23 induction in ER stressed DCs stimulated with PAMPs was IRE1α/X-box binding protein 1-dependent upon zymosan stimulation. Interestingly, we further evidenced PERK-mediated and CAAT/enhancer-binding protein β-dependent trans-activation of IL23A upon lipopolysaccharide treatment. Our findings uncover that the ER stress response can potently modulate cytokine expression in PAMP-stimulated human DCs.

  9. X-ray diffraction enhanced imaging study of intraocular tumors in human beings

    International Nuclear Information System (INIS)

    Tan Gao; Wang Huaqiao; Chen Yu; Yuan Qing; Li Gang; Zhu Peiping; Zhang Xiaodan; Zhong Xiufeng; Tang Jintian

    2010-01-01

    Diffraction enhanced imaging (DEI) with edge enhancement is suitable for the observation of weakly absorbing objects. The potential ability of the DEI was explored for displaying the microanatomy and pathology of human eyeball in this work. The images of surgical specimens from malignant intraocular tumor of hospitalized patients were taken using the hard X-rays from the topography station of Beamline 4W1A at Beijing Synchrotron Radiation Facility (BSRF). The obtained radiographic images were analyzed in correlation with those of pathology. The results show that the anatomic and pathologic details of intraocular tumors in human beings can be observed clearly by DEI for the first time, with good visualization of the microscopic details of eyeball ring such as sclera, choroid and other details of intraocular organelles. And the best resolution of DEI images reaches up to the magnitude of several tens of μm. The results suggest that it is capable of exhibiting clearly the details of intraocular tumor using DEI method. (authors)

  10. Enhanced reactivation and mutagenesis of UV-irradiated adenovirus in normal human fibroblasts

    International Nuclear Information System (INIS)

    Bennett, C.B.; Rainbow, A.J.

    1988-01-01

    UV-enhanced reactivation (UVER) and UV-enhanced mutagenesis (UVEM) for two adenovirus temperature-sensitive mutants were examined following the infection of normal human fibroblasts. UV-irradiation of the virus alone resulted in dose-dependent increase in the UV-induced reversion frequency (RF) of viral progeny and a dose-dependent exponential decrease in progeny survival, when infecting non-irradiated cells. Analysis of the slopes of the UV-induced reversion curves suggested that 2.5 ± 0.3 and 2.4 ± 0.5 'hits' were required to produce a targeted reversion event among the viral progeny of Ad5ts36 and Ad5ts125 respectively. UV-irradiation of cells 24 h prior to infection resulted in a significant increase in progeny survival for UV-irradiated virus (UVER factor = 3.4 ± 0.8) concomitant with a significant increase in RF for UV-irradiated virus (targeted increase = 1.9 ± 0.3). The UV-induced RF per lethal hit to the virus was also significantly greater in UV-irradiated compared with non-irradiated cells. These results are consistent with the existence of a UV-inducible error-prone DNA repair mechanism in normal human cells. (author)

  11. Laminin enhances the growth of human neural stem cells in defined culture media

    Directory of Open Access Journals (Sweden)

    Lathia Justin D

    2008-07-01

    Full Text Available Abstract Background Human neural stem cells (hNSC have the potential to provide novel cell-based therapies for neurodegenerative conditions such as multiple sclerosis and Parkinson's disease. In order to realise this goal, protocols need to be developed that allow for large quantities of hNSC to be cultured efficiently. As such, it is important to identify factors which enhance the growth of hNSC. In vivo, stem cells reside in distinct microenvironments or niches that are responsible for the maintenance of stem cell populations. A common feature of niches is the presence of the extracellular matrix molecule, laminin. Therefore, this study investigated the effect of exogenous laminin on hNSC growth. Results To measure hNSC growth, we established culture conditions using B27-supplemented medium that enable neurospheres to grow from human neural cells plated at clonal densities. Limiting dilution assays confirmed that neurospheres were derived from single cells at these densities. Laminin was found to increase hNSC numbers as measured by this neurosphere formation. The effect of laminin was to augment the proliferation/survival of the hNSC, rather than promoting the undifferentiated state. In agreement, apoptosis was reduced in dissociated neurospheres by laminin in an integrin β1-dependent manner. Conclusion The addition of laminin to the culture medium enhances the growth of hNSC, and may therefore aid their large-scale production.

  12. IL-29 Enhances CXCL10 Production in TNF-α-stimulated Human Oral Epithelial Cells.

    Science.gov (United States)

    Hosokawa, Yoshitaka; Hosokawa, Ikuko; Shindo, Satoru; Ozaki, Kazumi; Matsuo, Takashi

    2017-08-01

    Interleukin-29 (IL-29) is a cytokine belonging to the Type III interferon family. It was recently detected in the gingival crevicular fluid of periodontitis patients. However, the role of IL-29 in the pathogenesis of periodontal disease remains unknown. The aim of this study was to examine the effects of IL-29 on C-X-C motif chemokine ligand 10 (CXCL10) production in human oral epithelial cells. We measured CXCL10 production in TR146 cells, which is a human oral epithelial cell line, using an enzyme-linked immunosorbent assay. We used a Western blot analysis to detect IL-29 receptor expression and the phosphorylation levels of signal transduction molecules, including p38 mitogen-activated protein kinases (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor (NF)- κB p65, in the TR146 cells. The TR146 cells expressed the IL-29 receptor. IL-29 induced CXCL10 production in the TR146 cells. IL-29 significantly enhanced CXCL10 production in tumor necrosis factor (TNF)-α-stimulated TR146 cells. The p38 MAPK, STAT3, and NF-κB pathways were found to be related to the IL-29-induced enhancement of CXCL10 production in TNF-α-stimulated TR146 cells. IL-29 promotes T helper 1-cell accumulation in periodontal lesions by inducing CXCL10 production in oral epithelial cells.

  13. Gold nanoparticles enhance the X-ray-induced degradation of human centrin 2 protein

    Energy Technology Data Exchange (ETDEWEB)

    Brun, Emilie [Laboratoire de Chimie Physique, CNRS UMR 8000, Universite Paris-Sud 11, Bat. 350, 91405 Orsay Cedex (France); Duchambon, Patricia; Blouquit, Yves [INSERM U759, Imagerie Integrative, Campus Universitaire d' Orsay, Bat. 112, Institut Curie, Centre de Recherche, Laboratoire R. Latarjet, Campus Universitaire d' Orsay, 91405 Orsay Cedex (France); Keller, Gerard [UMR CNRS 8612, Physico-Chimie-Pharmacotechnie-Biopharmacie, Universite Paris 11, Faculte de Pharmacie, 5 rue Jean-Baptiste Clement, 92296 Chatenay-Malabry (France); Sanche, Leon [Groupe en Sciences des Radiations, Departement de Medecine Nucleaire et Radiobiologie, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4 (Canada); Sicard-Roselli, Cecile [Laboratoire de Chimie Physique, CNRS UMR 8000, Universite Paris-Sud 11, Bat. 350, 91405 Orsay Cedex (France)], E-mail: cecile.sicard@u-psud.fr

    2009-03-15

    In the war against cancer, radiotherapy is a prominent tool but counterbalanced by the fact that it also induces damages in healthy tissues. Nanotechnologies could open a new possibility to decrease these side effects. In particular, gold nanoparticles (GNPs) could be used as radio-sensitizers. As the role of proteins in the processes leading to cell death cannot be neglected, their radio-sensitization by GNPs is of great interest. This is particularly true in the case of the human centrin 2 protein, which has been proposed to be involved in DNA repair processes. To investigate this effect, we quantified for the first time the degradation of this protein in a gold colloidal solution when submitted to X-rays. We showed that the X-ray-induced degradation of the human centrin 2 protein is enhanced 1.5-fold in the presence of GNPs, even though no covalent bond exists between protein and GNPs. Among the conditions tested, the maximum enhancement was found with the higher GNP:protein ratio of 2x10{sup -4} and with the higher X-ray energy of 49 keV.

  14. Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds.

    Science.gov (United States)

    Hlavaty, K A; Gibly, R F; Zhang, X; Rives, C B; Graham, J G; Lowe, W L; Luo, X; Shea, L D

    2014-07-01

    Islet transplantation represents a potential cure for type 1 diabetes, yet the clinical approach of intrahepatic delivery is limited by the microenvironment. Microporous scaffolds enable extrahepatic transplantation, and the microenvironment can be designed to enhance islet engraftment and function. We investigated localized trophic factor delivery in a xenogeneic human islet to mouse model of islet transplantation. Double emulsion microspheres containing exendin-4 (Ex4) or insulin-like growth factor-1 (IGF-1) were incorporated into a layered scaffold design consisting of porous outer layers for islet transplantation and a center layer for sustained factor release. Protein encapsulation and release were dependent on both the polymer concentration and the identity of the protein. Proteins retained bioactivity upon release from scaffolds in vitro. A minimal human islet mass transplanted on Ex4-releasing scaffolds demonstrated significant improvement and prolongation of graft function relative to blank scaffolds carrying no protein, and the release profile significantly impacted the duration over which the graft functioned. Ex4-releasing scaffolds enabled better glycemic control in animals subjected to an intraperitoneal glucose tolerance test. Scaffolds releasing IGF-1 lowered blood glucose levels, yet the reduction was insufficient to achieve euglycemia. Ex4-delivering scaffolds provide an extrahepatic transplantation site for modulating the islet microenvironment to enhance islet function posttransplant. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Gold nanoparticles enhance the X-ray-induced degradation of human centrin 2 protein

    International Nuclear Information System (INIS)

    Brun, Emilie; Duchambon, Patricia; Blouquit, Yves; Keller, Gerard; Sanche, Leon; Sicard-Roselli, Cecile

    2009-01-01

    In the war against cancer, radiotherapy is a prominent tool but counterbalanced by the fact that it also induces damages in healthy tissues. Nanotechnologies could open a new possibility to decrease these side effects. In particular, gold nanoparticles (GNPs) could be used as radio-sensitizers. As the role of proteins in the processes leading to cell death cannot be neglected, their radio-sensitization by GNPs is of great interest. This is particularly true in the case of the human centrin 2 protein, which has been proposed to be involved in DNA repair processes. To investigate this effect, we quantified for the first time the degradation of this protein in a gold colloidal solution when submitted to X-rays. We showed that the X-ray-induced degradation of the human centrin 2 protein is enhanced 1.5-fold in the presence of GNPs, even though no covalent bond exists between protein and GNPs. Among the conditions tested, the maximum enhancement was found with the higher GNP:protein ratio of 2x10 -4 and with the higher X-ray energy of 49 keV

  16. Low perceived social support and post-myocardial infarction prognosis in the enhancing recovery in coronary heart disease clinical trial: the effects of treatment.

    Science.gov (United States)

    Burg, Matthew M; Barefoot, John; Berkman, Lisa; Catellier, Diane J; Czajkowski, Susan; Saab, Patrice; Huber, Marc; DeLillo, Vicki; Mitchell, Pamela; Skala, Judy; Taylor, C Barr

    2005-01-01

    In post hoc analyses, to examine in low perceived social support (LPSS) patients enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial (n = 1503), the pattern of social support following myocardial infarction (MI), the impact of psychosocial intervention on perceived support, the relationship of perceived support at the time of MI to subsequent death and recurrent MI, and the relationship of change in perceived support 6 months after MI to subsequent mortality. Partner status (partner, no partner) and score (12 = moderate support) on the ENRICHD Social Support Instrument (ESSI) were used post hoc to define four levels of risk. The resulting 4 LPSS risk groups were compared on baseline characteristics, changes in social support, and medical outcomes to a group of concurrently enrolled acute myocardial infarction patients without depression or LPSS (MI comparison group, n = 408). Effects of treatment assignment on LPSS and death/recurrent MI were also examined. All 4 LPSS risk groups demonstrated improvement in perceived support, regardless of treatment assignment, with a significant treatment effect only seen in the LPSS risk group with no partner and moderate support at baseline. During an average 29-month follow-up, the combined end point of death/nonfatal MI was 10% in the MI comparison group and 23% in the ENRICHD LPSS patients; LPSS conferred a greater risk in unadjusted and adjusted models (HR = 1.74-2.39). Change in ESSI score and/or improvement in perceived social support were not found to predict subsequent mortality. Baseline LPSS predicted death/recurrent MI in the ENRICHD cohort, independent of treatment assignment. Intervention effects indicated a partner surrogacy role for the interventionist and the need for a moderate level of support at baseline for the intervention to be effective.

  17. Bidirectional enhancing activities between human T cell leukemia-lymphoma virus type I and human cytomegalovirus in human term syncytiotrophoblast cells cultured in vitro.

    Science.gov (United States)

    Tóth, F D; Aboagye-Mathiesen, G; Szabó, J; Liu, X; Mosborg-Petersen, P; Kiss, J; Hager, H; Zdravkovic, M; Andirkó, I; Aranyosi, J

    1995-12-01

    The syncytiotrophoblast layer of the human placenta has an important role in limiting transplacental viral spread from mother to fetus. Human cytomegalovirus (HCMV) is capable of establishing a latent infection in syncytiotrophoblast cells, with restriction of gene expression to immediate-early and early proteins. We analyzed the extent of replication of human T cell leukemia-lymphoma virus type I (HTLV-I) in human term syncytiotrophoblasts infected with HTLV-I alone or coinfected with HTLV-I and HCMV. Although syncytiotrophoblasts could be infected with cell-free HTLV-I, no viral protein expression was found in the singly infected cells. On the contrary, coinfection of the cells with HTLV-I and HCMV resulted in simultaneous replication of both viruses. Bidirectional enhancing activities between HTLV-I and HCMV were mediated primarily by the Tax and immediate-early proteins, respectively. The stimulatory effect of HTLV-I Tax on HCMV replication appeared to be mediated partly by tumor necrosis factor beta and transforming growth factor beta-1. We observed formation of pseudotypes with HTLV-I nucleocapsids within HCMV envelopes, whereas HCMV was not pseudotyped by HTLV-I envelopes in dually infected syncytiotrophoblast cells. Our data suggest that in vivo dual infection of syncytiotrophoblast cells with HTLV-I and HCMV may facilitate the transplacental transmission of both viruses.

  18. Cholinergic enhancement of visual attention and neural oscillations in the human brain.

    Science.gov (United States)

    Bauer, Markus; Kluge, Christian; Bach, Dominik; Bradbury, David; Heinze, Hans Jochen; Dolan, Raymond J; Driver, Jon

    2012-03-06

    Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Enhancement of esculetin on Taxol-induced apoptosis in human hepatoma HepG2 cells

    International Nuclear Information System (INIS)

    Kuo, H.-C.; Lee, H.-J.; Hu, C.-C.; Shun, H.-I; Tseng, T.-H.

    2006-01-01

    The potential use of low dose chemotherapy has been appealing since lower dosages are more attainable during cancer therapy and cause less toxicity in patients. Combination therapy of Taxol, a promising frontline chemotherapy agent, with natural anti-tumor agents that are considerably less toxic with a capability of activating additional apoptotic signals or inhibiting survival signals may provide a rational molecular basis for novel chemotherapeutic strategies. Esculetin, a well-known lipoxygenase inhibitor, showed an inhibitory effect on the cell cycle progression of HL-60 cells in our previous study. In this report, the effects of a concomitant administration of esculetin and Taxol were investigated in human hepatoma HepG2 cells. Firstly, esculetin alone could exert an antiproliferation effect together with an inhibitory effect on the activation of ERKs and p38 MAPK. As compared to the treatment with Taxol only, a co-administration with esculetin and Taxol could result in a further enhancement of apoptosis as revealed by DNA fragmentation assay and Annexin-V-based assay. Meanwhile, immunoblotting analysis also showed that the co-administration of esculetin and Taxol could increase the expression of Bax and the cytosolic release of cytochrome C and enhance the expression of Fas and Fas ligand while the activation of caspase-8 and caspase-3 was also increased. Finally, the ERK cascade was proven to be involved in the enhancement of esculetin on the Taxol-induced apoptosis

  20. Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Zhengzhi, E-mail: zouzhengzhi@m.scnu.edu.cn [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000 (China); Luo, Xiaoyong [Department of Oncology, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang 471000 (China); Nie, Peipei [KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510000 (China); Wu, Baoyan; Zhang, Tao; Wei, Yanchun [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000 (China); Wang, Wenyi [Xiamen Cancer Center, Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361000 (China); Geng, Guojun; Jiang, Jie [Xiamen Cancer Center, Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen 361000 (China); Mi, Yanjun, E-mail: myjgj_77@163.com [Xiamen Cancer Center, Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361000 (China)

    2016-09-09

    SRC-3 is widely expressed in multiple tumor types and involved in cancer cell proliferation and apoptosis. Histone deacetylase (HDAC) inhibitors are promising antitumor drugs. However, the poor efficacy of HDAC inhibitors in solid tumors has restricted its further clinical application. Here, we reported the novel finding that depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors (SAHA and romidepsin). In contrast, overexpression of SRC-3 decreased SAHA-induced cancer cell apoptosis. Furthermore, we found that SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. The combination of bufalin and SAHA was particular efficient in attenuating AKT activation and reducing Bcl-2 levels. Taken together, these accumulating data might guide development of new breast and lung cancer therapies. - Highlights: • Depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors. • Overexpression of SRC-3 enhanced cancer cell resistance to HDAC inhibitors. • SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. • Bufalin synergized with HDAC inhibitor attenuated AKT activation and reduced Bcl-2 levels in human cancer cell.

  1. Three Experiments Examining the Use of Electroencephalogram,Event-Related Potentials, and Heart-Rate Variability for Real-Time Human-Centered Adaptive Automation Design

    Science.gov (United States)

    Prinzel, Lawrence J., III; Parasuraman, Raja; Freeman, Frederick G.; Scerbo, Mark W.; Mikulka, Peter J.; Pope, Alan T.

    2003-01-01

    Adaptive automation represents an advanced form of human-centered automation design. The approach to automation provides for real-time and model-based assessments of human-automation interaction, determines whether the human has entered into a hazardous state of awareness and then modulates the task environment to keep the operator in-the-loop , while maintaining an optimal state of task engagement and mental alertness. Because adaptive automation has not matured, numerous challenges remain, including what the criteria are, for determining when adaptive aiding and adaptive function allocation should take place. Human factors experts in the area have suggested a number of measures including the use of psychophysiology. This NASA Technical Paper reports on three experiments that examined the psychophysiological measures of event-related potentials, electroencephalogram, and heart-rate variability for real-time adaptive automation. The results of the experiments confirm the efficacy of these measures for use in both a developmental and operational role for adaptive automation design. The implications of these results and future directions for psychophysiology and human-centered automation design are discussed.

  2. Heart Failure

    OpenAIRE

    McMurray, John; Ponikowski, Piotr

    2011-01-01

    Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure.

  3. An enhanced heterologous virus-like particle for human papillomavirus type 16 tumour immunotherapy.

    Directory of Open Access Journals (Sweden)

    Khairunadwa Jemon

    Full Text Available Cervical cancer is caused by high-risk, cancer-causing human papillomaviruses (HPV and is the second highest cause of cancer deaths in women globally. The majority of cervical cancers express well-characterized HPV oncogenes, which are potential targets for immunotherapeutic vaccination. Here we develop a rabbit haemorrhagic disease virus (RHDV virus-like particle (VLP-based vaccine designed for immunotherapy against HPV16 positive tumours. An RHDV-VLP, modified to contain the universal helper T cell epitope PADRE and decorated with an MHC I-restricted peptide (aa 48-57 from the HPV16 E6, was tested for its immunotherapeutic efficacy against the TC-1 HPV16 E6 and E7-expressing tumour in mice. The E6-RHDV-VLP-PADRE was administered therapeutically for the treatment of a pre-existing TC-1 tumour and was delivered with antibodies either to deplete regulatory T cells (anti-CD25 or to block T cell suppression mediated through CTLA-4. As a result, the tumour burden was reduced by around 50% and the median survival time of mice to the humane endpoint was almost doubled the compared to controls. The incorporation of PADRE into the RHDV-VLP was necessary for an E6-specific enhancement of the anti-tumour response and the co-administration of the immune modifying antibodies contributed to the overall efficacy of the immunotherapy. The E6-RHDV-VLP-PADRE shows immunotherapeutic efficacy, prolonging survival for HPV tumour-bearing mice. This was enhanced by the systemic administration of immune-modifying antibodies that are commercially available for use in humans. There is potential to further modify these particles for even greater efficacy in the path to development of an immunotherapeutic treatment for HPV precancerous and cancer stages.

  4. Types of Heart Failure

    Science.gov (United States)

    ... Introduction Types of Heart Failure Classes of Heart Failure Heart Failure in Children Advanced Heart Failure • Causes and ... and procedures related to heart disease and stroke. Heart Failure Questions to Ask Your Doctor Use these questions ...

  5. Lectin enhancement of the lipofection efficiency in human lung carcinoma cells.

    Science.gov (United States)

    Yanagihara, K; Cheng, P W

    1999-10-18

    Poor transfection efficiency of human lung carcinoma cells by lipofection begs further development of more efficient gene delivery strategies. The purpose of this study was to determine whether lectins can improve the lipofection efficiency in lung carcinoma cells. A549, Calu3, and H292 cells grown to 90% confluence were transfected for 18 h with a plasmid DNA containing a beta-galactosidase reporter gene (pCMVlacZ) using lipofectin plus a lectin as the vector. Ten different lectins, which exhibit a wide range of carbohydrate-binding specificities, were examined for their abilities to enhance the efficiency of lipofection. The transfected cells were assessed for transfection efficiency by beta-galactosidase activity (units/microg protein) and % blue cells following X-Gal stain. Lipofectin supplemented with Griffonia simplicifolia-I (GS-I) yields largest enhancement of the lipofection efficiency in A549 and Calu3 cells (5.3- and 28-fold, respectively). Maackia amurensis gives the largest enhancement (6.5-fold) of lipofection efficiency in H292 cells. The transfection efficiency correlates with the amounts of DNA delivered to the nucleus. Binding of FITC-labeled GS-I and the enhancement of the lipofection efficiency by GS-I were inhibited by alpha-methyl-D-galactopyranoside, indicating an alpha-galactoside-mediated gene transfer to lung carcinoma cells. We conclude that lectin-facilitated lipofection is an efficient gene delivery strategy. Employment of cell type-specific lectins may allow for efficient cell type-specific gene targeting.

  6. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    Science.gov (United States)

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Does D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Helga Rodrigues

    Full Text Available The treatment of anxiety is on the edge of a new era of combinations of pharmacologic and psychosocial interventions. A new wave of translational research has focused on the use of pharmacological agents as psychotherapy adjuvants using neurobiological insights into the mechanism of the action of certain psychological treatments such as exposure therapy. Recently, d-cycloserine (DCS an antibiotic used to treat tuberculosis has been applied to enhance exposure-based treatment for anxiety and has proved to be a promising, but as yet unproven intervention. The present study aimed to evaluate the efficacy of DCS in the enhancement of exposure therapy in anxiety disorders. A systematic review/meta-analysis was conducted. Electronic searches were conducted in the databases ISI-Web of Science, Pubmed and PsycINFO. We included only randomized, double-blind, placebo-controlled trials with humans, focusing on the role of DCS in enhancing the action of exposure therapy for anxiety disorders. We identified 328 references, 13 studies were included in our final sample: 4 on obsessive-compulsive disorder, 2 on panic disorder, 2 on social anxiety disorder, 2 on posttraumatic stress disorder, one on acrophobia, and 2 on snake phobia. The results of the present meta-analysis show that DCS enhances exposure therapy in the treatment of anxiety disorders (Cohen d =  -0.34; CI: -0.54 to -0.14, facilitating the specific process of extinction of fear. DCS seems to be effective when administered at a time close to the exposure therapy, at low doses and a limited number of times. DCS emerges as a potential new therapeutic approach for patients with refractory anxiety disorders that are unresponsive to the conventional treatments available. When administered correctly, DCS is a promising strategy for augmentation of CBT and could reduce health care costs, drop-out rates and bring faster relief to patients.

  8. Identification of a novel human deoxynivalenol metabolite enhancing proliferation of intestinal and urinary bladder cells

    Science.gov (United States)

    Warth, Benedikt; Del Favero, Giorgia; Wiesenberger, Gerlinde; Puntscher, Hannes; Woelflingseder, Lydia; Fruhmann, Philipp; Sarkanj, Bojan; Krska, Rudolf; Schuhmacher, Rainer; Adam, Gerhard; Marko, Doris

    2016-09-01

    The mycotoxin deoxynivalenol (DON) is an abundant contaminant of cereal based food and a severe issue for global food safety. We report the discovery of DON-3-sulfate as a novel human metabolite and potential new biomarker of DON exposure. The conjugate was detectable in 70% of urine samples obtained from pregnant women in Croatia. For the measurement of urinary metabolites, a highly sensitive and selective LC-MS/MS method was developed and validated. The method was also used to investigate samples from a duplicate diet survey for studying the toxicokinetics of DON-3-sulfate. To get a preliminary insight into the biological relevance of the newly discovered DON-sulfates, in vitroexperiments were performed. In contrast to DON, sulfate conjugates lacked potency to suppress protein translation. However, surprisingly we found that DON-sulfates enhanced proliferation of human HT-29 colon carcinoma cells, primary human colon epithelial cells (HCEC-1CT) and, to some extent, also T24 bladder cancer cells. A proliferative stimulus, especially in tumorigenic cells raises concern on the potential impact of DON-sulfates on consumer health. Thus, a further characterization of their toxicological relevance should be of high priority.

  9. Enhanced stimulus-induced gamma activity in humans during propofol-induced sedation.

    Directory of Open Access Journals (Sweden)

    Neeraj Saxena

    Full Text Available Stimulus-induced gamma oscillations in the 30-80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABAA agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans.

  10. Ecological and human impact assessment in the legacy enhanced and naturally occurring radiation areas - human and ecological impact assessment in the legacy enhanced and naturally occurring radiation areas

    Energy Technology Data Exchange (ETDEWEB)

    Mrdakovic Popic, Jelena [Norwegian Radiation Protection Authority, P.O. Box 55, N-1332 Oesteraas (Norway); Salbu, Brit; Skipperud, Lindis [Norwegian University of Life Sciences, Centre for Environmental radioactivity CERAD, P.O. Box 5003, 1430 Aas (Norway)

    2014-07-01

    The Fen Complex in Norway is an area well-known with its specific magmatic bedrock rich in thorium (Th), iron (Fe), niobium (Nb) and rare earth elements (REE). During several past centuries, intensive mining was conducted at sites in the area, giving rise to enhanced radioactivity levels. Previous human health studies demonstrated exposure doses among the highest in Europe. In the current work, contamination status with respect to radionuclides ({sup 232}Th, uranium ({sup 238}U)) and trace elements (arsenic (As), chromium (Cr) and lead (Pb)) and possible impact on humans and biota were investigated at legacy NORM and undisturbed surrounding NOR rich sites in the Fen Complex area. Significantly heterogeneous radionuclides ({sup 232}Th, {sup 238}U, and daughters) distribution was found in soil at both legacy NORM and undisturbed NOR rich sites. Thorium activity concentration levels exceeded screening levels for radioactive waste material given by Norwegian Pollution Control Act. Based on sequential extraction results, mobility of {sup 232}Th and trace elements were low, although higher at legacy NORM than at undisturbed NOR rich sites. Uranium was present at considerable levels (up to 50 %) in pH and redox sensitive soil fraction, as well as bound to soil organic compounds. However, no further transport towards biggest water source Norsjoe Lake was observed, as concentration levels of all investigated elements in water samples were extremely low. Long-term surveys of outdoor terrestrial gamma dose rates, thoron ({sup 220}Rn) and radon ({sup 222}Rn) concentrations in the air demonstrated elevated values (up to 9.2 μGy/h, 5000 Bq/m{sup 3} and 200 Bq/m{sup 3}, respectively) with significant seasonal variation. Calculated annual exposure doses to humans due to outdoor exposure could exceed 10 mSv, i.e., be higher than 1 mSv dose constraint given by ICRP. Roughly summarized with previously published data on indoor doses for Fen village population, total annual exposure

  11. Enhanced replication of attenuated HSV-1 in irradiated human glioma xenografts

    International Nuclear Information System (INIS)

    Advani, Sunil J.; Kataoka, Yasushi; Sibley, Greg S.; Song, Paul Y.; Hallahan, Dennis E.; Roizman, Bernard; Weichselbaum, Ralph R.

    1997-01-01

    Purpose: Previously we had shown that combining ionizing radiation (IR) with attenuated replication competent HSV-1 (R3616) significantly increased glioma xenograft eradication compared to IR or virus alone. One hypothesis is that IR induces cell factors that contribute to augment viral replication thereby increasing the efficacy of attenuated HSV-1. The purpose of this study was to examine if IR altered viral replication of attenuated HSV-1 in glioma xenografts Material and Methods: Human U-87MG glioma cells were grown in the hindlimb of athymic mice and grown to >200 mm 3 . Tumors were infected with 2x10 7 plaque forming units (pfu) of R3616 ( γ1 34.5 - ) or R7020 (multimutated, γ1 34.5 + ) on day 0 and irradiated with 20 Gy on day 1 and 25 Gy on day 2. Tumors were harvested 3, 5, 7, and 14 days after viral injection. Tumors were homogenized and sonnicated. Serial dilutions of tumor extract were overlaid on Vero cells to determine the number of pfu. In addition, in-situ hybridization to HSV-1 DNA was performed on tumors harvested at day 7. Results: In-situ hybridization revealed larger numbers of glial cells infected with HSV along with a greater distribution in the irradiated tumors compared to non-irradiated tumors. We next quantified viral particles in infected tumors +/- IR: Conclusion: Herein we demonstrate radiation enhanced viral replication as one of the interactive effects of combining IR and attenuated HSV in treating glioma xenografts and a potential therapeutic motif in the treatment of gliomas. To reduce normal tissue toxicity of HSV in glioma therapy, viruses must be attenuated. However, attenuating the virus compromises its replication and thus its potential efficacy. Our results indicate that IR augments the amount of virus recovered from human glioma xenografts for up to 3 days post IR. The results do not appear to be related to a specific mutation in the herpes genome but rather to herpes viruses in general. Yields of R7020 were greater than R

  12. Enhanced uptake of multiple sclerosis-derived myelin by THP-1 macrophages and primary human microglia.

    Science.gov (United States)

    Hendrickx, Debbie A E; Schuurman, Karianne G; van Draanen, Michael; Hamann, Jörg; Huitinga, Inge

    2014-03-31

    The pathological hallmark of multiple sclerosis (MS) is myelin phagocytosis. It remains unclear why microglia and macrophages demyelinate axons in MS, but previously found or yet-unknown changes in the myelin of MS patients could contribute to this process. We therefore studied whether myelin from normal-appearing white matter (NAWM) of MS donors is phagocytosed more efficiently than myelin from control donors. Myelin was isolated from 11 MS and 12 control brain donors and labeled with the pH-sensitive fluorescent dye pHrodo to quantify uptake in lysosomes. Phagocytosis by differentiated THP-1 macrophages and by primary human microglia was quantified with flow cytometry. Whereas myelin uptake by THP-1 macrophages reached a plateau after approximately 24 hours, uptake by primary human microglia showed an almost linear increase over a 72-hour period. Data were statistically analyzed with the Mann-Whitney U test. MS-derived myelin was phagocytosed more efficiently by THP-1 macrophages after 6-hour incubation (P = 0.001 for the percentage of myelin-phagocytosing cells and P = 0.0005 for total myelin uptake) and after 24-hour incubation (P = 0.0006 and P = 0.0001, respectively), and by microglia after 24-hour incubation (P = 0.0106 for total myelin uptake). This enhanced uptake was not due to differences in the oxidation status of the myelin. Interestingly, myelin phagocytosis correlated negatively with the age of myelin donors, whereas the age of microglia donors showed a positive trend with myelin phagocytosis. Myelin isolated from normal-appearing white matter of MS donors was phagocytosed more efficiently than was myelin isolated from control brain donors by both THP-1 macrophages and primary human microglia. These data indicate that changes in MS myelin might precede phagocyte activation and subsequent demyelination in MS. Identifying these myelin changes responsible for enhancing phagocytic ability could be an interesting therapeutic target to

  13. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  14. Replacement of C305 in heart/muscle-type isozyme of human carnitine palmitoyltransferase I with aspartic acid and other amino acids.

    Science.gov (United States)

    Matsuo, Taisuke; Yamamoto, Atsushi; Yamamoto, Takenori; Otsuki, Kaoru; Yamazaki, Naoshi; Kataoka, Masatoshi; Terada, Hiroshi; Shinohara, Yasuo

    2010-04-01

    Liver- and heart/muscle-type isozymes of human carnitine palmitoyltransferase I (L- and M-CPTI, respectively) show a certain similarity in their amino acid sequences, and mutation studies on the conserved amino acids between these two isozymes often show essentially the same effects on their enzymatic properties. Earlier mutation studies on C305 in human M-CPTI and its counterpart residue, C304, in human L-CPTI showed distinct effects of the mutations, especially in the aspect of enzyme stability; however, simple comparison of these effects on the conserved Cys residue between L- and M-CPTI was difficult, because these studies were carried out using different expression systems and distinct amino acids as replacements. In the present study, we carried out mutation studies on the C305 in human M-CPTI using COS cells for the expression system. Our results showed that C305 was replaceable with aspartic acid but that substitution with other amino acids caused both loss of function and reduced expression.

  15. Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Sang Soo Kim

    Full Text Available We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2 in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2 and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2 generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms.We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC. The streptozotocin (STZ murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study.Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold. Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively.The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal

  16. An Enhancement of Campaign Posters for Human Error Prevention in NPPs

    International Nuclear Information System (INIS)

    Lee, Yong Hee; Lee, Yong Hee; Kwon, Soon Il

    2010-01-01

    Accidents in high reliability systems such as nuclear power plants (NPPs) give rise to not only a loss of property and life, but also social problems. One of the most frequently used techniques