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Combining physiological relevance and throughput for in vitro cardiac contractility measurement
(2020)
Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these.
Muscular activity in terms of surface electromyography (sEMG) is usually normalised to maximal voluntary isometric contractions (MVICs). This study aims to compare two different MVIC-modes in handcycling and examine the effect of moving average window-size. Twelve able-bodied male competitive triathletes performed ten MVICs against manual resistance and four sport-specific trials against fixed cranks. sEMG of ten muscles [M. trapezius (TD); M. pectoralis major (PM); M. deltoideus, Pars clavicularis (DA); M. deltoideus, Pars spinalis (DP); M. biceps brachii (BB); M. triceps brachii (TB); forearm flexors (FC); forearm extensors (EC); M. latissimus dorsi (LD) and M. rectus abdominis (RA)] was recorded and filtered using moving average window-sizes of 150, 200, 250 and 300 ms. Sport-specific MVICs were higher compared to manual resistance for TB, DA, DP and LD, whereas FC, TD, BB and RA demonstrated lower values. PM and EC demonstrated no significant difference between MVIC-modes. Moving average window-size had no effect on MVIC outcomes. MVIC-mode should be taken into account when normalised sEMG data are illustrated in handcycling. Sport-specific MVICs seem to be suitable for some muscles (TB, DA, DP and LD), but should be augmented by MVICs against manual/mechanical resistance for FC, TD, BB and RA.
In this study, we describe the manufacturing and characterization of silk fibroin membranes derived from the silkworm Bombyx mori. To date, the dissolution process used in this study has only been researched to a limited extent, although it entails various potential advantages, such as reduced expenses and the absence of toxic chemicals in comparison to other conventional techniques. Therefore, the aim of this study was to determine the influence of different fibroin concentrations on the process output and resulting membrane properties. Casted membranes were thus characterized with regard to their mechanical, structural and optical assets via tensile testing, SEM, light microscopy and spectrophotometry. Cytotoxicity was evaluated using BrdU, XTT, and LDH assays, followed by live–dead staining. The formic acid (FA) dissolution method was proven to be suitable for the manufacturing of transparent and mechanically stable membranes. The fibroin concentration affects both thickness and transparency of the membranes. The membranes did not exhibit any signs of cytotoxicity. When compared to other current scientific and technical benchmarks, the manufactured membranes displayed promising potential for various biomedical applications. Further research is nevertheless necessary to improve reproducible manufacturing, including a more uniform thickness, less impurity and physiological pH within the membranes.
Purpose
This study aims to investigate the biomechanics of handcycling during a continuous load trial (CLT) to assess the mechanisms underlying fatigue in upper body exercise.
Methods
Twelve able-bodied triathletes performed a 30-min CLT at a power output corresponding to lactate threshold in a racing recumbent handcycle mounted on a stationary ergometer. During the CLT, ratings of perceived exertion (RPE), tangential crank kinetics, 3D joint kinematics, and muscular activity of ten muscles of the upper extremity and trunk were examined using motion capturing and surface electromyography.
Results
During the CLT, spontaneously chosen cadence and RPE increased, whereas crank torque decreased. Rotational work was higher during the pull phase. Peripheral RPE was higher compared to central RPE. Joint range of motion decreased for elbow-flexion and radial-duction. Integrated EMG (iEMG) increased in the forearm flexors, forearm extensors, and M. deltoideus (Pars spinalis). An earlier onset of activation was found for M. deltoideus (Pars clavicularis), M. pectoralis major, M. rectus abdominis, M. biceps brachii, and the forearm flexors.
Conclusion
Fatigue-related alterations seem to apply analogously in handcycling and cycling. The most distal muscles are responsible for force transmission on the cranks and might thus suffer most from neuromuscular fatigue. The findings indicate that peripheral fatigue (at similar lactate values) is higher in handcycling compared to leg cycling, at least for inexperienced participants. An increase in cadence might delay peripheral fatigue by a reduced vascular occlusion. We assume that the gap between peripheral and central fatigue can be reduced by sport-specific endurance training.
We compare four different algorithms for automatically estimating the muscle fascicle angle from ultrasonic images: the vesselness filter, the Radon transform, the projection profile method and the gray level cooccurence matrix (GLCM). The algorithm results are compared to ground truth data generated by three different experts on 425 image frames from two videos recorded during different types of motion. The best agreement with the ground truth data was achieved by a combination of pre-processing with a vesselness filter and measuring the angle with the projection profile method. The robustness of the estimation is increased by applying the algorithms to subregions with high gradients and performing a LOESS fit through these estimates.
The problem of creation and use of sorption materials is of current interest for the practice of the modern medicine and agriculture. Practical importance is production of a biostimulant using a carbon sorbent for a significant increase in productivity, which is very relevant for the regions of Kazakhstan. It is known that a plant phytohormone—fusicoccin—in nanogram concentrations transforms cancer cells to the state of apoptosis. In this regard, there is a scientific practical interest in the development of a highly efficient method for producing fusicoccin from extract of germinated wheat seeds. According to the results of computer modeling, cleaning composite components of fusicoccin using microporous carbon adsorbents not suitable as the size of the molecule of fusicoccin more than micropores and the optimum pore size for purification of constituents of fusicoccin was determined by computer simulation.
BACKGROUND: Muscle stretch reflexes are widely used to examine neural muscle function. The knowledge of reflex response in muscles crossing the shoulder is limited. OBJECTIVE: To quantify reflex modulation according to various subject postures and different procedures of muscle pre-activation steering. METHODS: Thirteen healthy male participants performed two sets of external shoulder rotation stretches in various positions and with different procedures of muscle pre-activation steering on an isokinetic dynamometer over a range of two different pre-activation levels. All stretches were applied with a dynamometer acceleration of 104∘/s2 and a velocity of 150∘/s. Electromyographical response was measured via sEMG. RESULTS: Consistent reflexive response was observed in all tested muscles in all experimental conditions. The reflex elicitation rate revealed a significant muscle main effect (F (5,288) = 2.358, ρ= 0.040; η2= 0.039; f= 0.637) and a significant test condition main effect (F (1,288) = 5.884, ρ= 0.016; η2= 0.020; f= 0.143). Reflex latency revealed a significant muscle pre-activation level main effect (F (1,274) = 5.008, ρ= 0.026; η2= 0.018; f= 0.469). CONCLUSION: Muscular reflexive response was more consistent in the primary internal rotators of the shoulder. Supine posture in combination with visual feedback of muscle pre-activation level enhanced the reflex elicitation rate.
Exercise training effectively mitigates aging-induced health and fitness impairments. Traditional training recommendations for the elderly focus separately on relevant physiological fitness domains, such as balance, flexibility, strength and endurance. Thus, a more holistic and functional training framework is needed. The proposed agility training concept integratively tackles spatial orientation, stop and go, balance and strength. The presented protocol aims at introducing a two-armed, one-year randomized controlled trial, evaluating the effects of this concept on neuromuscular, cardiovascular, cognitive and psychosocial health outcomes in healthy older adults. Eighty-five participants were enrolled in this ongoing trial. Seventy-nine participants completed baseline testing and were block-randomized to the agility training group or the inactive control group. All participants undergo pre- and post-testing with interim assessment after six months. The intervention group currently receives supervised, group-based agility training twice a week over one year, with progressively demanding perceptual, cognitive and physical exercises. Knee extension strength, reactive balance, dual task gait speed and the Agility Challenge for the Elderly (ACE) serve as primary endpoints and neuromuscular, cognitive, cardiovascular, and psychosocial meassures serve as surrogate secondary outcomes. Our protocol promotes a comprehensive exercise training concept for older adults, that might facilitate stakeholders in health and exercise to stimulate relevant health outcomes without relying on excessively time-consuming physical activity recommendations.
To prevent the reduction of muscle mass and loss of strength coming along with the human aging process, regular training with e.g. a leg press is suitable. However, the risk of training-induced injuries requires the continuous monitoring and controlling of the forces applied to the musculoskeletal system as well as the velocity along the motion trajectory and the range of motion. In this paper, an adaptive norm-optimal iterative learning control algorithm to minimize the knee joint loadings during the leg extension training with an industrial robot is proposed. The response of the algorithm is tested in simulation for patients with varus, normal and valgus alignment of the knee and compared to the results of a higher-order iterative learning control algorithm, a robust iterative learning control and a recently proposed conventional norm-optimal iterative learning control algorithm. Although significant improvements in performance are made compared to the conventional norm-optimal iterative learning control algorithm with a small learning factor, for the developed approach as well as the robust iterative learning control algorithm small steady state errors occur.
The paper presents a method for the quantitative assessment of choroidal blood flow using an OCT-A system. The developed technique for processing of OCT-A scans is divided into two stages. At the first stage, the identification of the boundaries in the selected portion was performed. At the second stage, each pixel mark on the selected layer was represented as a volume unit, a voxel, which characterizes the region of moving blood. Three geometric shapes were considered to represent the voxel. On the example of one OCT-A scan, this work presents a quantitative assessment of the blood flow index. A possible modification of two-stage algorithm based on voxel scan processing is presented.