Biomedical Physiology and Kinesiology, Department of

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Estimating Body Segment Parameters from Three-dimensional Human Body Scans

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Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2022-01-05
Abstract: 

Body segment parameters are inputs for a range of applications. Participant-specific estimates of body segment parameters are desirable as this requires fewer prior assumptions and can reduce outcome measurement errors. Commonly used methods for estimating participant-specific body segment parameters are either expensive and out of reach (medical imaging), have many underlying assumptions (geometrical modelling) or are based on a specific subset of a population (regression models). Our objective was to develop a participant-specific 3D scanning and body segmentation method that estimates body segment parameters without any assumptions about the geometry of the body, ethnic background, and gender, is low-cost, fast, and can be readily available. Using a Microsoft Kinect Version 2 camera, we developed a 3D surface scanning protocol that enabled the estimation of participant-specific body segment parameters. To evaluate our system, we performed repeated 3D scans of 21 healthy participants (10 male, 11 female). We used open source tools to segment each body scan into 16 segments (head, torso, abdomen, pelvis, left and right hand, forearm, upper arm, foot, shank and thigh) and wrote custom software to estimate each segment’s mass, mass moment of inertia in the three principal orthogonal axes relevant to the center of the segment, longitudinal length, and center of mass. We compared our body segment parameter estimates to those obtained using two comparison methods and found that our system was consistent in estimating total body volume between repeated scans (male p = 0.1194, female p = 0.2240), estimated total body mass without significant differences when compared to our comparison method and a medical scale (male p = 0.8529, female p = 0.6339), and generated consistent and comparable estimates across a range of the body segment parameters of interest. Our work here outlines and provides the code for an inexpensive 3D surface scanning method for estimating a range of participant-specific body segment parameters.

Document type: 
Article

The L1624Q Variant in SCN1A Causes Familial Epilepsy Through a Mixed Gain and Loss of Channel Function

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Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-12-02
Abstract: 

Variants of the SCN1A gene encoding the neuronal voltage-gated sodium channel NaV1.1 cause over 85% of all cases of Dravet syndrome, a severe and often pharmacoresistent epileptic encephalopathy with mostly infantile onset. But with the increased availability of genetic testing for patients with epilepsy, variants in SCN1A have now also been described in a range of other epilepsy phenotypes. The vast majority of these epilepsy-associated variants are de novo, and most are either nonsense variants that truncate the channel or missense variants that are presumed to cause loss of channel function. However, biophysical analysis has revealed a significant subset of missense mutations that result in increased excitability, further complicating approaches to precision pharmacotherapy for patients with SCN1A variants and epilepsy. We describe clinical and biophysical data of a familial SCN1A variant encoding the NaV1.1 L1624Q mutant. This substitution is located on the extracellular linker between S3 and S4 of Domain IV of NaV1.1 and is a rare case of a familial SCN1A variant causing an autosomal dominant frontal lobe epilepsy. We expressed wild-type (WT) and L1642Q channels in CHO cells. Using patch-clamp to characterize channel properties at several temperatures, we show that the L1624Q variant increases persistent current, accelerates fast inactivation onset and decreases current density. While SCN1A-associated epilepsy is typically considered a loss-of-function disease, our results put L1624Q into a growing set of mixed gain and loss-of-function variants in SCN1A responsible for epilepsy.

Document type: 
Article

Accuracy of Kinovea Software in Estimating Body Segment Movements During Falls Captured on Standard Video: Effects of Fall Direction, Camera Perspective and Video Calibration Technique

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Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-10-25
Abstract: 

Falls are a major cause of unintentional injuries. Understanding the movements of the body during falls is important to the design of fall prevention and management strategies, including exercise programs, mobility aids, fall detectors, protective gear, and safer environments. Video footage of real-life falls is increasingly available, and may be used with digitization software to extract kinematic features of falls. We examined the validity of this approach by conducting laboratory falling experiments, and comparing linear and angular positions and velocities measured from 3D motion capture to estimates from Kinovea 2D digitization software based on standard surveillance video (30 Hz, 640x480 pixels). We also examined how Kinovea accuracy depended on fall direction, camera angle, filtering cut-off frequency, and calibration technique. For a camera oriented perpendicular to the plane of the fall (90 degrees), Kinovea position data filtered at 10 Hz, and video calibration using a 2D grid, mean root mean square errors were 0.050 m or 9% of the signal amplitude and 0.22 m/s (7%) for vertical position and velocity, and 0.035 m (6%) and 0.16 m/s (7%) for horizontal position and velocity. Errors in angular measures averaged over 2-fold higher in sideways than forward or backward falls, due to out-of-plane movement of the knees and elbows. Errors in horizontal velocity were 2.5-fold higher for a 30 than 90 degree camera angle, and 1.6-fold higher for calibration using participants’ height (1D) instead of a 2D grid. When compared to 10 Hz, filtering at 3 Hz caused velocity errors to increase 1.4-fold. Our results demonstrate that Kinovea can be applied to 30 Hz video to measure linear positions and velocities to within 9% accuracy. Lower accuracy was observed for angular kinematics of the upper and lower limb in sideways falls, and for horizontal measures from 30 degree cameras or 1D height-based calibration.

Document type: 
Article

Protein Kinases Mediate Anti-Inflammatory Effects of Cannabidiol and Estradiol Against High Glucose in Cardiac Sodium Channels

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Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-04-28
Abstract: 

Background: Cardiovascular anomalies are predisposing factors for diabetes-induced morbidity and mortality. Recently, we showed that high glucose induces changes in the biophysical properties of the cardiac voltage-gated sodium channel (Nav1.5) that could be strongly correlated to diabetes-induced arrhythmia. However, the mechanisms underlying hyperglycemia-induced inflammation, and how inflammation provokes cardiac arrhythmia, are not well understood. We hypothesized that inflammation could mediate the high glucose-induced biophyscial changes on Nav1.5 through protein phosphorylation by protein kinases A and C. We also hypothesized that this signaling pathway is, at least partly, involved in the cardiprotective effects of cannabidiol (CBD) and 17β-estradiol (E2).

Methods and Results: To test these ideas, we used Chinese hamster ovarian (CHO) cells transiently co-transfected with cDNA encoding human Nav1.5 α-subunit under control, a cocktail of inflammatory mediators or 100 mM glucose conditions (for 24 h). We used electrophysiological experiments and action potential modeling. Inflammatory mediators, similar to 100 mM glucose, right shifted the voltage dependence of conductance and steady-state fast inactivation and increased persistent current leading to computational prolongation of action potential (hyperexcitability) which could result in long QT3 arrhythmia. We also used human iCell cardiomyocytes derived from inducible pluripotent stem cells (iPSC-CMs) as a physiologically relevant system, and they replicated the effects produced by inflammatory mediators observed in CHO cells. In addition, activators of PK-A or PK-C replicated the inflammation-induced gating changes of Nav1.5. Inhibitors of PK-A or PK-C, CBD or E2 mitigated all the potentially deleterious effects provoked by high glucose/inflammation.

Conclusion: These findings suggest that PK-A and PK-C may mediate the anti-inflammatory effects of CBD and E2 against high glucose-induced arrhythmia. CBD, via Nav1.5, may be a cardioprotective therapeutic approach in diabetic postmenopausal population.

Document type: 
Article

The Energy of Muscle Contraction. III. Kinetic Energy During Cyclic Contractions

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Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-04-07
Abstract: 

During muscle contraction, chemical energy is converted to mechanical energy when ATP is hydrolysed during cross-bridge cycling. This mechanical energy is then distributed and stored in the tissue as the muscle deforms or is used to perform external work. We previously showed how energy is distributed through contracting muscle during fixed-end contractions; however, it is not clear how the distribution of tissue energy is altered by the kinetic energy of muscle mass during dynamic contractions. In this study we conducted simulations of a 3D continuum muscle model that accounts for tissue mass, as well as force-velocity effects, in which the muscle underwent sinusoidal work-loop contractions coupled with bursts of excitation. We found that increasing muscle size, and therefore mass, increased the kinetic energy per unit volume of the muscle. In addition to greater relative kinetic energy per cycle, relatively more energy was also stored in the aponeurosis, and less was stored in the base material, which represented the intra and extracellular tissue components apart from the myofibrils. These energy changes in larger muscles due to greater mass were associated lower mass-specific mechanical work output per cycle, and this reduction in mass-specific work was greatest for smaller initial pennation angles. When we compared the effects of mass on the model tissue behaviour to that of in situ muscle with added mass during comparable work-loop trials, we found that greater mass led to lower maximum and higher minimum acceleration in the longitudinal (x) direction near the middle of the muscle compared to at the non-fixed end, which indicates that greater mass contributes to tissue non-uniformity in whole muscle. These comparable results for the simulated and in situ muscle also show that this modelling framework behaves in ways that are consistent with experimental muscle. Overall, the results of this study highlight that muscle mass is an important determinant of whole muscle behaviour.

Document type: 
Article

Utility of Zebrafish Models of Acquired and Inherited Long QT Syndrome

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Peer reviewed: 
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Date created: 
2021-01-15
Abstract: 

Long-QT Syndrome (LQTS) is a cardiac electrical disorder, distinguished by irregular heart rates and sudden death. Accounting for ∼40% of cases, LQTS Type 2 (LQTS2), is caused by defects in the Kv11.1 (hERG) potassium channel that is critical for cardiac repolarization. Drug block of hERG channels or dysfunctional channel variants can result in acquired or inherited LQTS2, respectively, which are typified by delayed repolarization and predisposition to lethal arrhythmia. As such, there is significant interest in clear identification of drugs and channel variants that produce clinically meaningful perturbation of hERG channel function. While toxicological screening of hERG channels, and phenotypic assessment of inherited channel variants in heterologous systems is now commonplace, affordable, efficient, and insightful whole organ models for acquired and inherited LQTS2 are lacking. Recent work has shown that zebrafish provide a viable in vivo or whole organ model of cardiac electrophysiology. Characterization of cardiac ion currents and toxicological screening work in intact embryos, as well as adult whole hearts, has demonstrated the utility of the zebrafish model to contribute to the development of therapeutics that lack hERG-blocking off-target effects. Moreover, forward and reverse genetic approaches show zebrafish as a tractable model in which LQTS2 can be studied. With the development of new tools and technologies, zebrafish lines carrying precise channel variants associated with LQTS2 have recently begun to be generated and explored. In this review, we discuss the present knowledge and questions raised related to the use of zebrafish as models of acquired and inherited LQTS2. We focus discussion, in particular, on developments in precise gene-editing approaches in zebrafish to create whole heart inherited LQTS2 models and evidence that zebrafish hearts can be used to study arrhythmogenicity and to identify potential anti-arrhythmic compounds.

Document type: 
Article

The Effect of Multidirectional Loading on Contractions of the M. Medial Gastrocnemius

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Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-01-18
Abstract: 

Research has shown that compression of muscle can lead to a change in muscle force. Most studies show compression to lead to a reduction in muscle force, although recent research has shown that increases are also possible. Based on methodological differences in the loading design between studies, it seems that muscle length and the direction of transverse loading influence the effect of muscle compression on force production. Thus, in our current study we implement these two factors to influence the effects of muscle loading. In contrast to long resting length of the medial gastrocnemius (MG) in most studies, we use a shorter MG resting length by having participant seated with their knees at a 90° angle. Where previous studies have used unidirectional loads to compress the MG, in this study we applied a multidirectional load using a sling setup. Multidirectional loading using a sling setup has been shown to cause muscle force reductions in previous research. As a result of our choices in experimental design we observed changes in the effects of muscle loading compared to previous research. In the present study we observed no changes in muscle force due to muscle loading. Muscle thickness and pennation angle showed minor but significant increases during contraction. However, no significant changes occurred between unloaded and loaded trials. Fascicle thickness and length showed different patterns of change compared to previous research. We show that muscle loading does not result in force reduction in all situations and is possibly linked to differences in muscle architecture and muscle length.

Document type: 
Article

How Aging Affects Visuomotor Adaptation and Retention in a Precision Walking Paradigm

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Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-01-12
Abstract: 

Motor learning is a lifelong process. However, age-related changes to musculoskeletal and sensory systems alter the relationship (or mapping) between sensory input and motor output, and thus potentially affect motor learning. Here we asked whether age affects the ability to adapt to and retain a novel visuomotor mapping learned during overground walking. We divided participants into one of three groups (n = 12 each) based on chronological age: a younger-aged group (20–39 years old); a middle-aged group (40–59 years old); and an older-aged group (60–80 years old). Participants learned a new visuomotor mapping, induced by prism lenses, during a precision walking task. We assessed retention one-week later. We did not detect significant effects of age on measures of adaptation or savings (defined as faster relearning). However, we found that older adults demonstrated reduced initial recall of the mapping, reflected by greater foot-placement error during the first adaptation trial one-week later. Additionally, we found that increased age significantly associated with reduced initial recall. Overall, our results suggest that aging does not impair adaptation and that older adults can demonstrate visuomotor savings. However, older adults require some initial context during relearning to recall the appropriate mapping.

Document type: 
Article

Biophysical Characterization of a Novel SCN5A Mutation Associated With an Atypical Phenotype of Atrial and Ventricular Arrhythmias and Sudden Death

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Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2020-12-22
Abstract: 

Background: Sudden cardiac death (SCD) is an unexpected death that occurs within an hour of the onset of symptoms. Hereditary primary electrical disorders account for up to 1/3 of all SCD cases in younger individuals and include conditions such as catecholaminergic polymorphic ventricular tachycardia (CPVT). These disorders are caused by mutations in the genes encoding cardiac ion channels, hence they are known as cardiac channelopathies. We identified a novel variant, T1857I, in the C-terminus of Nav1.5 (SCN5A) linked to a family with a CPVT-like phenotype characterized by atrial tachy-arrhythmias and polymorphic ventricular ectopy occurring at rest and with adrenergic stimulation, and a strong family history of SCD.

Objective: Our goal was to functionally characterize the novel Nav1.5 variant and determine a possible link between channel gating and clinical phenotype.

Methods: We first used electrocardiogram recordings to visualize the patient cardiac electrical properties. Then, we performed voltage-clamp of transiently transfected CHO cells. Lastly, we used the ventricular/atrial models to visualize gating defects on cardiac excitability.

Results: Voltage-dependences of both activation and inactivation were right-shifted, the overlap between activation and inactivation predicted increased window currents, the recovery from fast inactivation was slowed, there was no significant difference in late currents, and there was no difference in use-dependent inactivation. The O’Hara-Rudy model suggests ventricular after depolarizations and atrial Grandi-based model suggests a slight prolongation of atrial action potential duration.

Conclusion: We conclude that T1857I likely causes a net gain-of-function in Nav1.5 gating, which may in turn lead to ventricular after depolarization, predisposing carriers to tachy-arrhythmias.

Document type: 
Article