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Filename: drivers/Session_files_driver.php
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File: /var/www/html/index.php
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Function: require_once
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Filename: controllers/Detail.php
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Function: _error_handler
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Introduction: Left ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism.
Methods And Results: We studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time-dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy).
Conclusion: This study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux.
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Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740402 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145937 | PLOS |
Gait Posture
December 2024
The Robert Jones and Agnes Hunt Orthopaedic Hospital, NHS Foundation Trust, Oswestry, SY10 7AG, United Kingdom; School of Pharmacy and Bioengineering, Keele University, Guy Hilton Research Centre, Thornburrow Drive, Stoke-on-Trent, ST4 7QB. Electronic address:
Background: Electromyography (EMG) can estimate the magnitude and timing of muscle activation during walking in those with gait disorders. Despite the potential of EMG use in assessment and clinical decision-making, there are reports of declining use of EMG within gait laboratories. Technical and educational barriers to EMG usage in clinics in Italy were recently suggested.
View Article and Find Full Text PDFJ Physiol
December 2024
Division of Reconstructive and Plastic Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
The frequent poor functional outcomes after delayed surgical repair of injured human peripheral nerves results in progressive downregulation of growth-associated genes in parallel with reduced neuronal regenerative capacity under each of the experimental conditions of chronic axotomy of neurones that remain without target contact, chronic distal nerve stump denervation, and chronic muscle denervation. Brief (1 h) low-frequency (20 Hz) electrical stimulation (ES) accelerates the outgrowth of regenerating axons across the surgical site of microsurgical repair of a transected nerve. Exercise programmes also promote nerve regeneration with the combination of ES and exercise being the most effective.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
December 2024
Muscle Physiology Laboratory, Department of Kinesiology, University of Massachusetts Amherst, MA 01003, USA.
The cause and consequences of inosine monophosphate (IMP) formation when ATP declines during muscular contractions are not fully understood. The purpose of this study was to examine the role of IMP formation in the maintenance of the Gibbs free energy for ATP hydrolysis (∆G) during dynamic contractions of increasing workload, and the implications of ATP loss . Eight males (27.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
December 2024
The population of older adults is exponentially expanding. Alongside aging comes the onset of chronic disease, decline of functional capacity, and reduced quality of life. Thus, this population increase will stress the capacity and financial viability of health and long-term care systems.
View Article and Find Full Text PDFCirc Cardiovasc Imaging
December 2024
Division of Cardiology, Heart Institute, Children's Hospital Colorado, Aurora (C.T.S., D.D.I., D.A.B.).
Background: Right ventricular-arterial coupling (RVAC) describes the relationship between right ventricular contractility and pulmonary vascular afterload. Noninvasive surrogates for RVAC using echocardiographic estimates of right ventricular function, such as tricuspid annular plane systolic excursion (TAPSE), have been shown to correlate with invasively measured RVAC and predict clinical outcomes in pediatric pulmonary arterial hypertension. However, given the limitations of TAPSE at accurately estimating right ventricular function in children, we hypothesized that a multivariable estimate of RVAC using right ventricular free-wall longitudinal strain (RVFW-LS) may perform better than those utilizing TAPSE at predicting clinical outcomes.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!