31 research outputs found

    Cardiosphere-derived cells demonstrate metabolic flexibility that Is influenced by adhesion status

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    Adult stem cells demonstrate metabolic flexibility that is regulated by cell adhesion status. The authors demonstrate that adherent cells primarily utilize glycolysis, whereas suspended cells rely on oxidative phosphorylation for their ATP needs. Akt phosphorylation transduces adhesion-mediated regulation of energy metabolism, by regulating translocation of glucose transporters (GLUT1) to the cell membrane and thus, cellular glucose uptake and glycolysis. Cell dissociation, a pre-requisite for cell transplantation, leads to energetic stress, which is mediated by Akt dephosphorylation, downregulation of glucose uptake, and glycolysis. They designed hydrogels that promote rapid cell adhesion of encapsulated cells, Akt phosphorylation, restore glycolysis, and cellular ATP levels

    Diffuse interstitial fibrosis assessed by cardiac magnetic resonance is associated with dispersion of ventricular repolarization in patients with hypertrophic cardiomyopathy

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    Background Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, disarray, fibrosis, and increased risk for ventricular arrhythmias. Increased QT dispersion has been reported in patients with HCM, but the underlying mechanisms have not been completely elucidated. In this study, we examined the relationship between diffuse interstitial fibrosis, replacement fibrosis, QTc dispersion and ventricular arrhythmias in patients with HCM. We hypothesized that fibrosis would slow impulse propagation and increase dispersion of ventricular repolarization, resulting in increased QTc dispersion on surface electrocardiogram (ECG) and ventricular arrhythmias. Methods ECG and cardiac magnetic resonance (CMR) image analyses were performed retrospectively in 112 patients with a clinical diagnosis of HCM. Replacement fibrosis was assessed by measuring late gadolinium (Gd) enhancement (LGE), using a semi-automated threshold technique. Diffuse interstitial fibrosis was assessed by measuring T1 relaxation times after Gd administration, using the Look?Locker sequence. QTc dispersion was measured digitally in the septal/anterior (V1?V4), inferior (II, III, and aVF), and lateral (I, aVL, V5, and V6) lead groups on surface ECG. Results All patients had evidence of asymmetric septal hypertrophy. LGE was evident in 70 (63%) patients; the median T1 relaxation time was 411±38æms. An inverse correlation was observed between T1 relaxation time and QTc dispersion in leads V1?V4 (p\u3c 0.001). Patients with HCM who developed sustained ventricular tachycardia had slightly higher probability of increased QTc dispersion in leads V1?V4 (odds ratio, 1.011 [1.004?1.0178, p=0.003). We found no correlation between presence and percentage of LGE and QTc dispersion. Conclusion Diffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1?V4

    Integration across time determines path deviation discrimination for moving objects.

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    YesBackground: Human vision is vital in determining our interaction with the outside world. In this study we characterize our ability to judge changes in the direction of motion of objects-a common task which can allow us either to intercept moving objects, or else avoid them if they pose a threat. Methodology/Principal Findings: Observers were presented with objects which moved across a computer monitor on a linear path until the midline, at which point they changed their direction of motion, and observers were required to judge the direction of change. In keeping with the variety of objects we encounter in the real world, we varied characteristics of the moving stimuli such as velocity, extent of motion path and the object size. Furthermore, we compared performance for moving objects with the ability of observers to detect a deviation in a line which formed the static trace of the motion path, since it has been suggested that a form of static memory trace may form the basis for these types of judgment. The static line judgments were well described by a 'scale invariant' model in which any two stimuli which possess the same two-dimensional geometry (length/width) result in the same level of performance. Performance for the moving objects was entirely different. Irrespective of the path length, object size or velocity of motion, path deviation thresholds depended simply upon the duration of the motion path in seconds. Conclusions/Significance: Human vision has long been known to integrate information across space in order to solve spatial tasks such as judgment of orientation or position. Here we demonstrate an intriguing mechanism which integrates direction information across time in order to optimize the judgment of path deviation for moving objects.Wellcome Trust, Leverhulme Trust, NI

    Cardiometabolic Syndrome: An Update on Available Mouse Models

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    Cardiometabolic syndrome (CMS), a disease entity characterized by abdominal obesity, insulin resistance (IR), hypertension, and hyperlipidemia, is a global epidemic with approximately 25% prevalence in adults globally. CMS is associated with increased risk for cardiovascular disease (CVD) and development of diabetes. Due to its multifactorial etiology, the development of several animal models to simulate CMS has contributed significantly to the elucidation of the disease pathophysiology and the design of therapies. In this review we aimed to present the most common mouse models used in the research of CMS. We found that CMS can be induced either by genetic manipulation, leading to dyslipidemia, lipodystrophy, obesity and IR, or obesity and hypertension, or by administration of specific diets and drugs. In the last decade, the ob/ob and db/db mice were the most common obesity and IR models, whereas Ldlr -/-and Apoe -/-were widely used to induce hyperlipidemia. These mice have been used either as a single transgenic or combined with a different background with or without diet treatment. High-fat diet with modifications is the preferred protocol, generally leading to increased body weight, hyperlipidemia, and IR. A plethora of genetically engineered mouse models, diets, drugs, or synthetic compounds that are available have advanced the understanding of CMS. However, each researcher should carefully select the most appropriate model and validate its consistency. It is important to consider the differences between strains of the same animal species, different animals, and most importantly differences to human when translating results. © 2021 Georg Thieme Verlag. All rights reserved

    Exercise training improves characteristics of exercise oscillatory ventilation in chronic heart failure

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    Background Exercise oscillatory ventilation in chronic heart failure has been suggested as a factor related to adverse cardiac events, aggravated prognosis and higher mortality. Exercise training is well known to affect exercise capacity and mechanisms of pathophysiology beneficially in chronic heart failure. Little is known, however, about the exercise training effects on characteristics of exercise oscillatory ventilation in chronic heart failure patients. Design and methods Twenty (out of 38) stable chronic heart failure patients exhibited exercise oscillatory ventilation (age 54 ± 11 years, peak oxygen uptake 15.0 ± 5.0 ml/kg per minute). Patients attended 36 sessions of high intensity interval exercise. All patients underwent cardiopulmonary exercise testing before and after the programme. Assessment of exercise oscillatory ventilation was based on the amplitude of cyclic fluctuations in breathing during rest and exercise. All values are mean ± SD. Results Exercise training reduced (P < 0.05) the percentage of exercise oscillatory ventilation duration (79.0 ± 13.0 to 50.0 ± 25.0%), while average amplitude (5.2 ± 2.0 to 4.9 ± 1.6 L/minute) and length (44.0 ± 10.9 to 41.0 ± 6.7 seconds) did not change (P > 0.05). Exercise oscillatory ventilation patients also increased exercise capacity (P < 0.05). Conclusions A rehabilitation programme based on high intensity interval training improved exercise oscillatory ventilation observed in chronic heart failure patients, as well as cardiopulmonary efficiency and functional capacity. © European Society of Cardiology 2017

    Skeletal muscle microcirculatory abnormalities are associated with exercise intolerance, ventilatory inefficiency, and impaired autonomic control in heart failure

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    Background: Several skeletal muscle abnormalities have been identified in patients with chronic heart failure (CHF), including endothelial dysfunction. We hypothesized that skeletal muscle microcirculation, assessed by near-infrared spectroscopy (NIRS), is impaired in CHF patients and is associated with disease severity. Methods: Eighty-three stable patients with mildmoderate CHF (72 males, mean age 54 ± 14 years, body mass index 26.7 ± 3.4 kg/m 2) and 8 healthy subjects, matched for age, gender and body mass index, underwent NIRS with the vascular occlusion technique and cardiopulmonary exercise testing (CPET) evaluation on the same day. Tissue oxygen saturation (StO 2, %), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured in the thenar muscle by NIRS before, during and after 3-minute occlusion of the brachial artery. Measurements included StO 2, oxygen consumption rate (OCR, %/min) and reperfusion rate (RR, %/min). All subjects underwent a symptom-limited CPET on a cycle ergometer. Measurements included VO 2 at peak exercise (VO 2peak, ml/kg/min) and anaerobic threshold (VO 2AT, ml/kg/min), VE/VCO 2 slope, chronotropic reserve (CR, %) and heart rate recovery (HRR 1, bpm). Results: CHF patients had significantly lower StO 2 (75 ± 8.2 vs 80.3 ± 6, p < 0.05), lower OCR (32.3 ± 10.4 vs 37.7 ± 5.5, p < 0.05) and lower RR (10 ± 2.8 vs 15.7 ± 6.3, p < 0.05) compared with healthy controls. CHF patients with RR <9.5 had a significantly greater VO 2peak (p < 0.001), VO 2AT (p < 0.01), CR (p = 0.01) and HRR 1 (p = 0.01), and lower VE/VCO 2 slope (p = 0.001), compared to those with RR <9.5. In a multivariate analysis, RR was identified as an independent predictor of VO 2peak, VE/VCO 2 slope and HRR 1. Conclusions: Peripheral muscle microcirculation, as assessed by NIRS, is significantly impaired in CHF patients and is associated with disease severity. © 2011 International Society for Heart and Lung Transplantation. All rights reserved

    Method used to detect, Define limits and Rate the Urban Zones

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    Quality of life management of living ressources. Key action n"5 : Sustainable agriculture, fisheries and forestry and integrated development of rural areas including mountain areasSIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : GR 2034 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

    Typology of Periurban Rural Areas and Analysis of their Diversity: Application to a Set of European Regions

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    Quality of life management of living ressources. Key action n"5 : Sustainable agriculture, fisheries and forestry and integrated development of rural areas including mountain areasSIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : GR 2035 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc
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