364 research outputs found
Handle Anywhere: A Mobile Robot Arm for Providing Bodily Support to Elderly Persons
Age-related loss of mobility and increased risk of falling remain important
obstacles toward facilitating aging-in-place. Many elderly people lack the
coordination and strength necessary to perform common movements around their
home, such as getting out of bed or stepping into a bathtub. The traditional
solution has been to install grab bars on various surfaces; however, these are
often not placed in optimal locations due to feasibility constraints in room
layout. In this paper, we present a mobile robot that provides an older adult
with a handle anywhere in space - "handle anywhere". The robot consists of an
omnidirectional mobile base attached to a repositionable handle. We analyze the
postural changes in four activities of daily living and determine, in each, the
body pose that requires the maximal muscle effort. Using a simple model of the
human body, we develop a methodology to optimally place the handle to provide
the maximum support for the elderly person at the point of most effort. Our
model is validated with experimental trials. We discuss how the robotic device
could be used to enhance patient mobility and reduce the incidence of falls.Comment: 8 pages, 10 figure
Platelet-mediated thrombosis in stenosed canine coronary arteries: Inhibition by nicergoline, a platelet-active alpha-adrenergic antagonist
The effects of nicergoline, a new agent that blocks alpha-adrenergic receptors and inhibits platelet phospholipase, were evaluated in a canine model of platelet-mediated coronary thrombosis. In 48 open chest dogs, the circumflex coronary artery was stenosed by plicating the artery wall with a suture. Thirty-four of the 48 dogs exhibited cyclic reductions in flow in the stenotic vessel, followed by a sudden return to control levels. The reductions in flow were unabated in all but two dogs after heparin administration (1,000 U/kg per h), unaffected by large doses of nitroglycerin and nifedipine and associated with platelet aggregates in the stenotic segment (demonstrated by histologic and electron microscopic examination). These observations support the conclusion that the flow reductions were caused by platelet aggregation rather than by fibrin deposition or vasospasm.Twenty dogs were monitored for 1 hour after heparin administration and then assigned to a control (n = 7) or nicergoline-treated (n = 13; 1 mg/kg intravenously) group. In control dogs, cyclic reductions in flow continued unchanged for another hour, whereas in the treated group they were markedly decreased in 1 dog and completely abolished in the other 12 dogs. Aspirin (30 mg/ kg intravenously) suppressed flow reductions in all control dogs, confirming the primary role of platelet aggregation in the phenomenon.This study provides a modified model of platelet-mediated thrombosis in stenosed coronary arteries. Furthermore, the results indicate that nicergoline can effectively interfere with platelet function in vivo. The potent antithrombotic activity exhibited by nicergoline might enhance the therapeutic usefulness of this vasodilator
THERAPY WITH ADULT BONE MARROW-DERIVED MESENCHYMAL STEM CELLS AMELIORATES DOXORUBICIN-INDUCED CARDIOMYOPATHY
Overcoming the roadblocks to cardiac cell therapy using tissue engineering
Transplantations of various stem cells or their progeny have repeatedly improved cardiac performance in animal models of myocardial injury; however, the benefits observed in clinical trials have been generally less consistent. Some of the recognized challenges are poor engraftment of implanted cells and, in the case of human cardiomyocytes, functional immaturity and lack of electrical integration, leading to limited contribution to the heart’s contractile activity and increased arrhythmogenic risks. Advances in tissue and genetic engineering techniques are expected to improve the survival and integration of transplanted cells, and to support structural, functional, and bioenergetic recovery of the recipient hearts. Specifically, application of a prefabricated cardiac tissue patch to prevent dilation and to improve pumping efficiency of the infarcted heart offers a promising strategy for making stem cell therapy a clinical reality.
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Human Cardiac Stem Cells Isolated from Atrial Appendages Stably Express c-kit
The in vivo studies of myocardial infarct using c-kit+/Lin− cardiac stem cells (CSCs) are still in the early stage with margin or no beneficial effects for cardiac function. One of the potential reasons may be related to the absence of fully understanding the properties of these cells both in vitro and in vivo. In the present study, we aimed to systematically examine how CSCs adapted to in vitro cell processes and whether there is any cell contamination after long-term culture. Human CSCs were enzymatically isolated from the atrial appendages of patients. The fixed tissue sections, freshly isolated or cultured CSCs were then used for identification of c-kit+/Lin− cells, detection of cell contamination, or differentiation of cardiac lineages. By specific antibody staining, we demonstrated that tissue sections from atrial appendages contained less than 0.036% c-kit+/Lin− cells. For the first time, we noted that without magnetic activated cell sorting (MACS), the percentages of c-kit+/Lin− cells gradually increased up to ∼40% during continuously culture between passage 2 to 8, but could not exceed >80% unless c-kit MACS was carried out. The resulting c-kit+/Lin− cells were negative for CD34, CD45, CD133, and Lin markers, but positive for KDR and CD31 in few patients after c-kit MACS. Lin depletion seemed unnecessary for enrichment of c-kit+/Lin− cell population. Following induced differentiation, c-kit+/Lin− CSCs demonstrated strong differentiation towards cardiomyocytes but less towards smooth and endothelial cells. We concluded that by using an enzymatic dissociation method, a large number, or higher percentage, of relative pure human CSCs with stable expression of c-kit+ could be obtained from atrial appendage specimens within ∼4 weeks following c-kit MACS without Lin depletion. This simple but cost-effective approach can be used to obtain enough numbers of stably-expressed c-kit+/Lin− cells for clinical trials in repairing myocardial infarction
Bovine herpesvirus 4-based vector delivering the full length xCT DNA efficiently protects mice from mammary cancer metastases by targeting cancer stem cells
An accurate, nontraumatic ultrasonic method to monitor myocardial wall thickening in patients undergoing cardiac surgery
AbstractMeasurement of systolic wall thickening by sonomicrometry provides an accurate index of regional left ventricular function, but the trauma of crystal insertion limits its widespread clinical use. The first clinical application of a 10 MHz ultrasonic Doppler probe that can be either sutured or applied by suction to the epicardium and can measure wall thickening at any depth of the left ventricular wall is described. In 18 dogs, measurements obtained with the suction probe correlated well (r = 0.97) with those of a previously validated sutured probe.To assess clinical feasibility, the probe was applied to the epicardium of patients undergoing coronary bypass surgery. Good quality wall thickening signals were obtained with no complications. Transmural left ventricular thickening fraction before bypass surgery was 34 ± 3% (mean value ± SE) at the mid-ventricular lateral wall, 33 ± 4% at the anterior basal wall and 26 ± 4% at the mid-ventricular posterior wall. Right ventricular thickening fraction averaged 25 ± 3%. Endocardial thickening fraction tended to exceed epicardial thickening fraction, although the difference attained statistical significance (p < 0.05) only at the anterior basal wall.On average, thickening fraction during the immediate postoperative period remained unchanged compared with the preoperutive values, but a marked individual variability was observed, with 7 of 15 patients exhibiting a decrease and 8 an increase. Exteriorization of the wires attached to the sutured probe allowed continuous in situ monitoring of wall thickening in the postoperative period and subsequent removal of the probe, in six patients the crystal was left in place for 48 to 72 h after surgery and then removed without complications; good wall thickening signals were obtained for the entire period during which the probe was implanted.Thus, the Doppler probe is an accurate, atraumatic method for measuring right and left ventricular regional function. Transmural, endocardial and epicardial function can be mapped at various sites during surgery, and postoperatively one can monitor serial changes of regional function and assess the effects of cardioplegia and other therapeutic interventions. This technique should be useful for both investigative and clinical purposes
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Circulating Biomarkers to Identify Responders in Cardiac Cell therapy.
Bone marrow mononuclear cell (BM-MNC) therapy in ST-elevation acute myocardial infarction (STEMI) has no biological inclusion criteria. Here, we analyzed 63 biomarkers and cytokines in baseline plasma samples from 77 STEMI patients treated with BM-MNCs in the TIME and Late-TIME trials as well as 61 STEMI patients treated with placebo. Response to cell therapy was defined by changes in left ventricular ejection fraction, systolic/diastolic volumes, and wall motion indexes. We investigated the clinical value of circulating proteins in outcome prediction using significance testing, partial least squares discriminant analysis, and receiver operating characteristic (ROC) analysis. Responders had higher biomarker levels (76-94% elevated) than non-responders. Several biomarkers had values that differed significantly (P < 0.05) between responders and non-responders including stem cell factor, platelet-derived growth factor, and interleukin-15. We then used these lead candidates for ROC analysis and found multiple biomarkers with values areas under the curve >0.70 including interleukin 15. These biomarkers were not involved in the placebo-treated subjects suggesting that they may have predictive power. We conclude that plasma profiling after STEMI may help identify patients with a greater likelihood of response to cell-based treatment. Prospective trials are needed to assess the predictive value of the circulating biomarkers
TGF-β1 enhances cardiomyogenic differentiation of skeletal muscle-derived adult primitive cells
The optimal medium for cardiac differentiation of adult primitive cells remains to be established. We quantitatively compared the efficacy of IGF-1, dynorphin B, insulin, oxytocin, bFGF, and TGF-beta1 in inducing cardiomyogenic differentiation. Adult mouse skeletal muscle-derived Sca1+/CD45-/c-kit-/Thy-1+ (SM+) and Sca1-/CD45-/c-kit-/Thy-1+ (SM-) cells were cultured in basic medium (BM; DMEM, FBS, IGF-1, dynorphin B) alone and BM supplemented with insulin, oxytocin, bFGF, or TGF-beta1. Cardiac differentiation was evaluated by the expression of cardiac-specific markers at the mRNA (qRT-PCR) and protein (immunocytochemistry) levels. BM+TGF-beta1 upregulated mRNA expression of Nkx2.5 and GATA-4 after 4 days and Myl2 after 9 days. After 30 days, BM+TGF-beta1 induced the greatest extent of cardiac differentiation (by morphology and expression of cardiac markers) in SM- cells. We conclude that TGF-beta1 enhances cardiomyogenic differentiation in skeletal muscle-derived adult primitive cells. This strategy may be utilized to induce cardiac differentiation as well as to examine the cardiomyogenic potential of adult tissue-derived stem/progenitor cells
Linear Accelerator Test Facility at LNF Conceptual Design Report
Test beam and irradiation facilities are the key enabling infrastructures for
research in high energy physics (HEP) and astro-particles. In the last 11 years
the Beam-Test Facility (BTF) of the DA{\Phi}NE accelerator complex in the
Frascati laboratory has gained an important role in the European
infrastructures devoted to the development and testing of particle detectors.
At the same time the BTF operation has been largely shadowed, in terms of
resources, by the running of the DA{\Phi}NE electron-positron collider. The
present proposal is aimed at improving the present performance of the facility
from two different points of view: extending the range of application for the
LINAC beam extracted to the BTF lines, in particular in the (in some sense
opposite) directions of hosting fundamental physics and providing electron
irradiation also for industrial users; extending the life of the LINAC beyond
or independently from its use as injector of the DA{\Phi}NE collider, as it is
also a key element of the electron/positron beam facility. The main lines of
these two developments can be identified as: consolidation of the LINAC
infrastructure, in order to guarantee a stable operation in the longer term;
upgrade of the LINAC energy, in order to increase the facility capability
(especially for the almost unique extracted positron beam); doubling of the BTF
beam-lines, in order to cope with the signicant increase of users due to the
much wider range of applications.Comment: 71 page
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