Kinesiology and Health Sciences

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https://uwspace.uwaterloo.ca/handle/10012/9862

This is the collection for the University of Waterloo's Department of Kinesiology and Health Sciences. It was known as the Department of Kinesiology until January 2021.

Research outputs are organized by type (eg. Master Thesis, Article, Conference Paper).

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Attentional effects on visual-tactile crossmodal enhancement at early stages of cortical processing
(University of Waterloo, 2024-09-12) Salazar, Esteban
Sensory processing can be facilitated through bimodal interactions between relevant visual-tactile sensory inputs in order to achieve goal-oriented behaviours. While the specific neural mechanisms contributing to this modulation remain unclear, the dorsolateral prefrontal cortex (DLPFC) may have a role in regulating the observed processing facilitation seen in the somatosensory cortex (S1), though the extent is not yet clear. We used electroencephalography (EEG) to observe the temporal contributions of visual priming to the enhancement of S1 responses. We hypothesized that inhibiting DLPFC cortical activity would result in a diminished facilitation of tactile processing in S1 (represented by the P50), observed by a visual-tactile stimuli onset with a 200-300 ms time delay. Somatosensory modulation was inferred through amplitude and latency shifts in tactile event-related potentials (ERPs) recorded while participants performed a sensory integration task that required scaled motor responses dependent on the amplitudes of tactile and visual stimuli. Tactile stimuli were discrete vibrations (25 Hz) presented to the left index finger, visual stimuli were presented as a central horizontal bar on a computer screen at varying heights, and graded motor responses were made by squeezing a pressure-sensitive rubber bulb. Healthy adults completed a training session to become familiar with the stimulus-response relationships for both visual and tactile stimuli prior to completing a task where pairs of discrete stimuli with random amplitudes were presented: Tactile-tactile (TT, 500 ms each, 30 ms ISI), visual-tactile with a 200-300 ms delay (vTd 200-300 ms), and visual-tactile with a 300-400 ms delay (vTd 300-400 ms). Stimuli pairs were administered in a block setting, where each block contained 60 trials, with 20 trials for each of the discrete stimuli presented in a randomized order. The study design consisted of 10 blocks, with a short transcranial magnetic stimulation (TMS) intervention at the halfway mark. Participants were randomly assigned to either an intervention group (n=16) or control group (n=16) where TMS modalities of theta burst stimulation (TBS); continuous TBS (cTBS) was given to the intervention group and intermittent TBS (iTBS) was given to the control group, both applied to the right DLPFC. Results revealed that P50 upregulation observed in condition vTd (200- 300 ms) is significantly lower following cTBS on the right DLPFC but still greater than unimodal TT stimulation. Following iTBS, bimodal facilitation was observed in condition vTd (300-400 ms) for P50 and N70. These findings improve our understanding of the role right DLPFC plays regarding crossmodal facilitation observed in visual-tactile processing.
SYMMETRY OF HIP, KNEE AND ANKLE JOINT POWER DURING CYCLING WITH AND WITHOUT PAIN FROM KNEE OSTEOARTHRITIS
(University of Waterloo, 2024-09-10) Currie, Daniel
Knee osteoarthritis (OA) is one of the most common chronic conditions in Canada (Bombardier et al., 2011). Commonly, the pain caused by knee OA is unequal between knees, which can lead to asymmetry of movement and joint power in daily activities. With hip and knee extensors generating the greatest proportion of power during cycling, it is unclear how the body will compensate if there is a painful knee (Elmer et al., 2011). The purpose of this study was to investigate if seat height, workload and, any difference in knee pain, affected asymmetry of power between hips, knees and ankles during cycling. Asymmetry was defined as the difference between the dominant versus non-dominant leg. It was hypothesized that bilateral joint power would become more symmetrical as seat height increased, workload decreased and any difference in knee pain decreased. Twenty-six participants aged 45-75 years, with and without knee OA completed six cycling bouts at three seat heights (20°, 30°, 40° minimum knee flexion angle) and two workloads (40W and 75W) on a commercial fit-bike (Pro 1, Purely Custom, USA). Self-reported knee pain on the Numeric Pain Rating Scale (NPRS) was recorded for each knee before the first bout and after each bout. Three-dimensional kinematics were collected with a commercial motion capture system (Optotrak Certus, NDI, Canada) and synchronized three-dimensional kinetics were collected with commercial instrumented 3-axis pedals (Science to Practice, Slovenia). Joint angles and power were calculated in Visual3D (HAS-Motion, Germantown, USA) for the full bout. From that full bout, a one-minute portion was selected. Then revolutions in that one-minute were averaged to one pedal cycle using custom Python code. Seat height and workload did not have a significant effect on symmetry of joint power. A significant relationship was found between hip, knee and ankle joint power difference and knee pain difference. The leg with the more painful knee produced less power than the opposite leg (p < 0.001, both workloads). Evaluating asymmetry for each joint revealed an interesting pattern. The more painful knee produced more joint power than the less painful knee (p = 0.003, 75W workload). The hip and ankle in the leg with the more painful knee produced less power than the contralateral joints (p < 0.001, both workloads). These results demonstrated the relationship between lower limb joint power and knee pain during cycling and in turn, how these joints could contribute power in the presence of knee pain. These findings are also relevant to rehabilitation clinicians, because they show rehabilitation could aim to boost the power produced by healthy joints to offload a symptomatic joint.
On the utility of a rotating swim bench as a freestyle swimming emulator
(University of Waterloo, 2024-08-30) Webster, Kathryn Frances
The swim bench is an isokinetic ergometer intended to aid competitive swimming training by replicating the underwater pull of the freestyle stroke. Yet limited literature addresses the biomechanical fidelity of the swim bench relative to in-water swimming (Olbrecht & Clarys, 1983; Piovezan et al., 2019). Further, the lack of body roll on the swim bench may limit simulation fidelity. Accordingly, the Kayak Pro SwimFast swim bench includes a rotating bench setting. Specific changes to a competitive swimmer’s kinematics and muscle activation patterns with a rotating setting is unknown. The purposes of this study were assessment of the influences of swim bench settings on kinematics and muscle recruitment, and exploration of the similarity of kinematic data between swim bench and in-water data sets. Fifteen collegiate and/or national level, male, competitive swimmers completed 8 sets (4 rotating and 4 fixed) of 30 second continuous freestyle stroke pulling on a Kayak Pro SwimFast swim bench. Surface electromyography of 12 right upper limb muscles and bilateral upper limb and torso kinematics were collected. Time-series swim bench kinematic and electromyographic data were compared using statistical parametric mapping, enabling holistic evaluation. The swim bench kinematics were compared to existing in-water data from McCabe (2008). Few kinematic and electromyographic differences existed between the rotating and fixed swim bench settings. Briefly, left shoulder elevation was higher on the rotating swim bench setting nearing the end of the push leading into the recovery phases of the freestyle swimming stroke (p = 0.08). The left shoulder axial rotation approached significance at during the push phase, with a higher internal rotation angle on the rotating setting. Right wrist radial deviation was greater on the fixed setting during the recovery phase (p = 0.024). Infraspinatus achieved greater activations on the fixed bench than the rotating during the late pull to early push phases (p = 0.012). Despite the device’s roll design, no differences existed in shoulder roll between the rotating or fixed setting and, regardless of bench setting, participants laterally flexed the torso, potentially as compensation for the overall lack of roll allowance. The similarities between settings indicated that the rotating setting may not substantially augment the realism of stroke mechanics on the swim bench. Compared to in-water swimming, the swim bench produced similar elbow flexion angles and maximum vertical depth at the third distal phalanx. However, entry phase duration phase decreased on the swim bench, while the pull, push, and recovery phases increased (p < 0.0001). Additionally, the stroke length, mediolateral stroke width range, and vertical stroke depth range, and total shoulder roll decreased (p = 0.0002, p < 0.0001, p < 0.0001, p < 0.0001). The differences between the stroke mechanics, lack of entry phase, and addition of the lateral torso flexion on the swim bench are notable considerations for swim bench use in training and research. Swimmers could develop associated habits that reduce swimming economy, and the results suggest that using the swim bench in training may not extrapolate to in-water swimming.
Sex Differences in the Physiological Response to the Modern Fire Environment
(University of Waterloo, 2024-08-30) Pulford-Thorpe, Alexis
Due to recent changes in building design and materials, modern structural fires tend towards a ‘ventilation-limited’ fire environment, resulting in globally low levels of oxygen (O2) and increased amounts of carbon monoxide (CO) and smoke. It is unknown how the dynamic hypoxic and hypercapnic environment as a result of the fire impacts an occupant’s physiological and cognitive ability to evacuate. Moreover, it is unknown if physiological sex differences in males and females may further impact egress abilities. This work explored the effects of this dynamic hypoxic and hypercapnic environment on the ability to egress by exposing males and females to sub-incapacitating levels of hypoxic and hypercapnic gases measured in large-scale ventilation-limited fires. Thirty participants (n=15 females) completed three testing days. Day 1 was a familiarization day, intended for participants to familiarize themselves with the experimental protocol of the egress scenario in ambient conditions. Day 2 consisted of five trials of the simulated evacuation scenario wherein real-time changes to O2 and CO2 were administered with CO saturations (%COHb) of 4% and 7%. Day 3 consisted of four trials of the simulated egress scenario wherein changes to O2 and CO2 were carried out in tandem and in isolation. The egress scenario consisted of the following 12.5 minute sequence: 1 min seated pre-test baseline, 5 mins seated, 3.5 mins walking, 4 mins walking carrying a 20lb weight and 2.5 mins seated post-test baseline. This scenario was intended to simulate a realistic evacuation of an occupant from a residential structure, however did not include the more dangerous fire elements (increased temperature, smoke and particulate matter). End-tidal gases, ventilation, heart rate and oxygen saturation were measured continuously. Response (decision, answer and reaction) time was assessed by participants answering a prompt every 15s throughout each trial. The prompts consisted of a directional EXIT sign in which participants had to select the arrow corresponding to the direction of the EXIT sign, as well as a modified Stroop Colour Test. Results demonstrate that females elicited a greater percent change within a condition compared to males for heart rate (p=0.04), tidal volume (p=0.03) and fraction of hemoglobin bound to oxygen (p=0.02). Physiological changes in responses for all participants were significantly greater during the hypercapnia egressing trials compared to hypoxia and control trials (Ventilation: 72±20 L/min, 34±8.9 L/min, 33±6.4 L/min, p< 0.05; tidal volume: 2.3±0.6L, 1.5±0.4, 1.4±0.3, p <0.05). Physiological responses during 4% COHb and 7% COHb trials did not differ other than the fraction of hemoglobin bound to oxygen during pre and post baselines (p<0.05). Overall, the presence of CO2 resulted in the greatest physiological response and coincided with a decrement in ability to complete the egress protocol. Smaller females appeared to be more affected by fire conditions during egress than males. These results indicate that the modern ventilation-limited fire environment results in physiological responses that could negatively impact an occupant’s ability to effectively evacuate.
Effects of posture and trunk muscle coordination on multi-joint isometric lifting strength: Implications for individualised movement assessment and intervention
(University of Waterloo, 2024-08-30) Pinto, Brendan Luke
The manner in which movement is executed can influence biomechanical demand and consequently the development of musculoskeletal disorders. Although modifying movement execution can help regulate biomechanical demand by influencing tissue loading and tolerance, it can also influence physical performance by influencing the ability to exert force. Movement-based interventions to regulate biomechanical demand that hinder physical performance can limit acceptability, sustainability, and effectiveness of the intervention. Conversely, interventions to enhance physical performance that modify movement execution in a way that imposes higher than necessary biomechanical demand, can hinder physical development and long-term performance. However, the development of comprehensive movement assessments and interventions that consider both the impact on biomechanical demand as well as physical performance is challenged by a scarcity of knowledge of how movement execution can influence physical performance in multi-joint tasks. The global aim of this thesis was to investigate how modifying posture and trunk muscle coordination can influence the ability to exert force during isometric lifting. Four studies were conducted to address the global thesis aim. Study 1 investigated the effects of modifying trunk inclination and low back curvature on isometric lifting strength as previous research has yet to clearly dissociate how these distinct postural characteristics could influence the ability to exert force in multi-joint tasks such as lifting from the ground. Results showed that modifying trunk inclination and low back curvature can influence strength in multi-joint tasks substantially and to a similar extent. However, the effect of modifying these postural characteristics interact and vary greatly across individuals in magnitude (up to 620N of isometric lifting force) and direction (increase/decrease). Thus, a single postural profile cannot be generalized as the strongest for every individual and the ability to exert force in multi-joint tasks cannot be inferred solely from posture. Additionally, the individually varying effects of posture on strength suggests that individuals can adapt through movement training to be stronger in postures that are favourable for tissue loading and tolerance. Assessing the L4/L5 joint contact forces of the observed postures suggested that the effect of posture on biomechanical loading is more consistent, and the biomechanical demand imposed by flexing the low back outweighs any potential acute gain in isometric lifting strength. Together this supports the recommendation to avoid highly flexed low back postures during demanding physical activities. Study 2 compared the immediate effects of a simple verbal directive and detailed trunk muscle bracing coaching on isometric lifting strength, low back postural displacement and trunk muscle co-contraction. Prior research has suggested that cueing co-contraction of all the trunk muscles can enhance the ability to exert force in multi-joint tasks but has not yet isolated the effect of modifying trunk muscle coordination on the ability to exert force which may potentially depend on the approach used to cue trunk muscle coordination. Detailed coaching which included a combination of verbal and physical cues was more effective than the simple verbal directive at increasing trunk muscle co-contraction (group mean co-contraction for the baseline, directive and coached condition was 10.1%, 11.0% and 13.5% respectively) and decreasing low back postural displacement (group mean change in low back flexion angle normalized to each individual’s maximum flexion range-of-motion for the baseline, directive and coached condition was 21.4%, 19.5% and 17.2% respectively). However, both cueing approaches immediately reduced isometric lifting strength to a similar extent (group mean peak isometric lifting force for the baseline, directive and coached condition was 1194 N, 1109 N and 1096 N respectively). Results indicate that detailed coaching is more effective than simple verbal directives at modifying trunk muscle coordination to restrict low back postural displacement but cautions cueing trunk muscle coordination for the first time in situations where peak force production is desired. Results also suggest that future research should confirm acquisition and transfer of the targeted trunk muscle coordination patterns as the full potential impact of modifying trunk muscle coordination may not be completely apparent from observing the immediate responses to cues. Motivated by the individually varying effects of posture on the ability to exert force observed in Study 1, Study 3 evaluated the extent to which proxies for leverage derived from kinematic quantities can statistically explain the individual variation in the effects of posture on the ability to exert isometric lifting force. Prior research has used kinematic-based proxies to describe and make inferences about how posture can influence leverage in multi-joint tasks. However, these approaches do not capture all the mechanics involved in multi-joint kinetics and the extent to which they may explain the individually varying effects of posture on the ability to exert force in a multi-joint task has not yet been tested. As expected, based on fundamental biomechanical principles, the kinematic-based proxies for leverage that were investigated (joint-to-external force moment arms and predicted joint-angle-dependent torque-generating capacities) explained a very low proportion of variation (<17%) in the effects of posture on isometric lifting force. In contrast, variables derived from both kinematic and kinetic measurements such as the net joint reaction moments calculated using a rigid linked segment model and inverse dynamics explained a higher proportion of variation in the effects of posture on the ability to exert isometric lifting force (approximately 80%). These results indicate that simplified kinematic-based approaches cannot be used to assess the effects of posture on leverage in multi-joint tasks on an individual basis. Instead, variables derived from both kinematic and kinetic measurements such as the net joint reaction moments show promise for being used in development of quantitative assessments of multi-joint leverage. Study 4 investigated whether individuals maintain their potential for physical performance when given instruction to avoid rounding the low back during light mass lifting. Compared to prior movement-based interventions such as the squat lift technique that vaguely describes whole body posture, targeting a key postural feature such as low back flexion is theoretically expected to afford greater flexibility to self-organize the rest of the body linkage to regulate biomechanical demand, without hindering physical performance. However, using simple verbal directives to cue specific movement features during low demand tasks may not acutely prompt individuals to prioritize physical performance as they self-organize, rendering the intervention ineffective. Although aggregate group level results indicated that low back postural instruction targeting biomechanical demand decreased low back flexion during crate lifting and increased isometric lifting strength in postures replicating those exhibited during crate lifting, there was high heterogeneity in responses. Among the 37 of 40 participants classified as individuals who could potentially benefit from decreasing their low back flexion, 15 and 22 participants were respectively classified as successful and unsuccessful in decreasing low back flexion in response to the instruction, to be within a range that minimizes passive tissue strain. Though replicating the crate lifting posture to assess isometric strength emerged to be challenging, there were individuals who increased (n=8), decreased (n=9) and did not change (n=23) isometric strength, independent of their low back postural response. Hence, although most participants appeared to maintain physical performance potential when given simple verbal directives that target low back flexion to regulate biomechanical demand, some participants responded in a manner that decreased performance potential and many did not successfully decrease their low back flexion within a range that minimizes passive tissue strain. This suggests a need for more detailed movement coaching and training in research and practice to effectively modify movement behaviour without hindering physical performance potential. Overall, the results from this thesis indicate that the effects of modifying posture and trunk muscle coordination on the ability to exert force in multi-joint tasks is complex and can greatly vary across individuals. Additionally, modifying movement execution may need to go beyond simple verbal directives to provide detailed movement coaching. The findings support that considering the effects of movement execution on physical performance has the potential to advance movement assessment and intervention strategies. Yet, there is a need to develop approaches to capture the individually varying effects of movement features such as posture on the ability to exert force in multi-joint tasks to develop strategies that can effectively regulate biomechanical demand without hindering physical performance as well as enhance physical performance without imposing unnecessary biomechanical demands.
The Effects of Single- and Dual-Energy Quantitative Computed Tomography on Volumetric Bone Mineral Density Assessment and Strain Analysis in the Proximal Humerus
(University of Waterloo, 2024-08-30) Beshay, Daniel
A common and difficult orthopedic injury, proximal humerus fractures frequently require surgery to restore functional shoulder motion. For optimal patient outcomes and to inform treatment choices, accurate evaluation of fracture stability and healing progress is essential. A thorough combination of the use of computational loads through finite element modeling (FEM) with innovative imaging methods to evaluate proximal humerus fractures was used to predict their fracture locations based on volumetric bone mineral density (vBMD). To quantify fracture characteristics, vBMD, and morphological changes related to proximal humerus fractures, 2 different imaging modalities were used. The effectiveness of single energy quantitative (SEQCT) and dual-energy quantitative computed tomography (DEQCT) was compared. BONE and STD reconstruction kernels, an algorithmic procedure, were parameters that were changed post-processing to alter the frequency content of images obtained from the SEQCT and DEQCT scanners. These imaging techniques enable a multidimensional study, giving rise to a deeper comprehension of fracture locations, bone quality, and provide preliminary steps to inform risk factors. To achieve this objective, fourteen cadaveric shoulders (n = 7 left, n = 7 right) were scanned under each scanning modality and post-processed into both BONE and STD reconstruction kernel, respectively. Four different images were created per shoulder scan: SEQCT BONE/STD and DEQCT BONE/STD, creating a total of 56 different possible images. Density in volumetric bone mineral density (vBMD) was calculated in the humeral head, metaphysis, and diaphysis regions, for each imaging modality. Image processing software was utilized to create 3D models of the humerus and highlighting the selected regions. Specimen-specific slope/intercept was used to convert from native Hounsfield Units (HU) to equivalent vBMD [mgK2HPO4/cm3]. Strain measurements were calculated using FEMs derived from each proximal humerus model and are reported as maximum and minimum principal strain through visual representations and histograms according to each region, showcasing differences in them between BONE and STD reconstruction kernel. BONE reconstruction kernel showcased higher values in both HU and vBMD measures than STD reconstruction kernel in SEQCT with significant differences seen respectively between reconstruction kernels in HU and vBMD (p < 0.05) in all three regions. Strong correlations (R2 = 0.99) between BONE and STD image-based density (HU and vBMD) by bone region (Humeral Head, Metaphysis, and Diaphysis) was observed in SEQCT. On the other hand, BONE reconstruction kernel vBMD was not higher than STD reconstruction kernel in all regions when looking at individual cadavers in DEQCT. Only the metaphysis showcased this whereas the diaphysis had four models that didn’t follow this trend and one model in the humeral head. vBMD differences arise from anatomical differences while scanning such either as a full torso or an isolated shoulder. Strong correlations (R2 = 0.99 & 0.98) between BONE and STD image-based density (vBMD) in the humeral head and metaphysis, respectively. The r-squared was lower in the diaphysis region (0.86). Fracture location predictions are possible from the FEM visual representation in both maximum/minimum principal strain with the aid of the figure showcasing strain levels in the three regions. These qualitative and respective quantitative data are cadaver dependent as each cadaver was influenced according to anatomical differences such as bone quality, comorbidities, age, patient activity levels and more. The FE models generated showcased that 7 out of the 7 models generated from SEQCT predict fracture location in the metaphysis region and 7 out of the 7 models generated from DEQCT also predict fracture location in the metaphysis region. As they clarify the significance of fracture morphology, bone quality, and loading circumstances on fracture location, the study's findings shed light on the relationship between imaging parameters and biomechanics of proximal humerus fractures. This research also seeks to assist physicians in choosing the best imaging approach for precise fracture characterization and treatment planning by comparing the performance of several imaging modalities. Ultimately, the combination of innovative imaging methods with finite element modeling can increase our ability to understand proximal humerus fractures by providing us knowledge on the optimal imaging modality, with the long-term objective of enabling better clinical outcomes for patients with these injuries through improved diagnostic and treatment options.
The Role of Low Back Capacities on Loaded and Unloaded Functional Movements: Squat and Lunge
(University of Waterloo, 2024-08-29) Zafar, Elizabeth
Variability of movement patterns across individuals have been well documented in healthy young adults. Large heterogeneity of movement patterns within seemingly homogenous populations suggests the possible presence of subgrouping of individuals. This variability makes it difficult to study and draw conclusions based on group effects, since group means may not be representative of individuals within the group, and especially when subgroups respond differently to interventions. It is also well established that certain movements and movement characteristics are relevant to movement efficiency, tissue exposure, and injury risk, however, it is not fully understood why individuals utilize certain movement patterns over others. It is plausible that physical capacity related differences between subgroups of individuals can help explain differences in movement. As such, this thesis aimed to cluster individuals according to their lumbar movement profiles during functional movements, and then relate characteristic profiles of each subgroup to the low back capacities of strength, muscular endurance, proprioception, and motor control. Additionally, this thesis investigated the effects of introducing a moderate challenge (i.e., loading) to the lumbar movement profiles during functional movements. Thirty-two healthy young adults (16 M, 16 F) performed two sets of ten repetitions each of squat (SQT) and lunge (LNG) in both unloaded (UL) and loaded (LD) conditions. Additionally, lumbar capacity tests of strength (S), endurance (E), joint position accuracy (P-A), joint position sensitivity (P-S), and motor control (MC) were assessed. State spaces of lumbar angle dynamics for each condition of movement were constructed, then discretized into 48 bins and averaged across repetitions. State spaces were then analyzed using spectral clustering with the number of subgroups selected based on the strongest silhouette score. Analyses of variance (ANOVAs) testing the effect of sex and group on each capacity test’s scores were conducted. The results of the clustering produced two groups with weak clustering strength in each condition. In both the SQT UL and SQT LD conditions, a significant interaction between sex and group in P-S (p = 0.01), and a significant effect of sex in E (p = 0.04)were found. In the LNG UL condition, a significant interaction between sex and group in P-A (p = 0.04), and a significant effect of sex in E (p = 0.04) were found. Significant interactions between group and sex were found in both P-S (p = 0.04) and MC (p = 0.03) for the LNG LD condition. Differences in lumbar capacities between groups were related to features of the state spaces, including shape, diffuseness, and intensity of attractors. This thesis highlighted the importance of physical capacities on movement patterns and affirmed the necessity of characterizing subgroups of individuals within a heterogeneous sample population. This thesis provides a framework for more comprehensive investigations into the relationships between specific capacities and movement profiles.
Cerebellar Contributions to Rapid Cross-Modal Attention in Visual-Tactile Processing
(University of Waterloo, 2024-08-28) Mughal, Simran
Clinical, functional connectivity, and behavioral studies have provided growing evidence for the involvement of the right lateral cerebellar hemisphere in cognition, especially attention. The presence of contralateral connections between the cerebellum and cerebrum via the thalamus provides the groundwork for cerebellar involvement in cognition and lateralization of function. At any given time, the brain is subjected to multiple relevant stimuli. While we cannot divide our attention between these stimuli, we can rapidly shift our focus. If these rapid attentional shifts occur in close temporal proximity between two target stimuli (T1 and T2), there is a decrease in accurately reporting the second target (T2). This phenomenon is termed attentional blink (AB). Studies combining continuous theta burst stimulation (cTBS) with visual AB tasks have shown that inhibiting the right cerebellar hemisphere enhances visual attentional blink. However, the exact physiological mechanisms underlying cerebellar influence on attentional networks during sensory processing remain unclear. It is also uncertain whether the cerebellum impacts sensory processing when presented with two relevant targets in different sensory modalities compared to unimodal conditions, and whether lateralization of function is conserved in this process. The aim of this study was to investigate the cerebellar involvement in cross-modal attentional processes and its impact on rapid attentional shifts when integrating cross-modal information presented within short time intervals. Hypothesizing that cross-modal AB would be enhanced following right cerebellar stimulation, 26 healthy participants underwent two sessions consisting of pre and post-cTBS cross-modal AB tasks targeting either the left or right cerebellar hemisphere. The task involved presenting either a visual or tactile stimulus (T1), followed by a stimulus of the opposite modality (T2), and then a mask of the same modality as T2. After stimulus presentation, participants were prompted to indicate the perceived side for both stimuli. Our results demonstrated that after transiently depressing the right cerebellar hemisphere, there was a significant reduction in extracting T2 tactile targets from the mask. Furthermore, there was an overall reduction in reporting T2 in the AB condition within the visual-tactile block type. There was no significant change in performance in either condition after stimulating the left cerebellar hemisphere. These results imply the cerebellum’s role as a sensory modulator in a hemisphere- specific way. Given our results, we conjecture that during complex tasks which require attentional control, the right cerebellum is recruited to manage bottom-up processing of the mask (distractors) via sensory gating. This allows top-down processes to effectively integrate T2 (target) after processing T1. We put forward the “Sensory Balance Model”, offering insights into the neurophysiological mechanisms underlying cerebellar involvement in attentional modulation.
From the lab to the cockpit: the development and analysis of quantifiable measures of goal-directed actions through gaze behaviour
(University of Waterloo, 2024-08-22) Ayala, Naila
Objectives: The goal of this thesis was to examine the utility of gaze behaviour as an indicator of information processing during the performance of complex tasks in ecological environments. Information processing is influenced by the interaction between task requirements, an individual’s resource availability, and the environmental context (i.e., modifying factors). Five experiments were performed that manipulated these modifying factors and examined the respective changes across low fidelity and high-fidelity environments. Study one comprehensively examined gaze behaviour while participants performed a neurocognitive test where task demands increased progressively by loading the working memory system (i.e., cognitive load). Studies two and three characterized gaze behaviours associated with increased sensorimotor task demands during the performance of simulated landing scenarios using a computer-based simulation and high-fidelity flight simulator, respectively. Study four aimed to explicitly assess differences in gaze behaviour between novices (i.e, ab-initio) and experts (i.e., licensed low-time pilots) during a simulated flight task, while study five expanded on findings from these studies by examining gaze behaviour during an extended (i.e., cruise and landing) flying scenario that involved a dual-task paradigm (i.e., cognitive load). Methods: Twenty-seven participants were recruited for study one. Task performance and eye movements were recorded as they completed the Tower of London task, which progressively increased in cognitive load by manipulating problem set size (i.e., minimum number of moves to solve the task). In studies two and three, sensorimotor difficulty was manipulated by altering the wind conditions during a landing scenario (i.e., no wind, turbulent winds). Eighteen participants in study two and twenty-nine participants in study three were recruited and had their gaze behaviour recorded during the task in a low-fidelity (i.e., PC-based) and high-fidelity (i.e., fully immersive flight training device) simulation environment, respectively. Study four examined gaze behaviour and performance differences during a simulated landing task between ab-initio pilots (i.e., 0 flight hours) and licensed low-time pilots (i.e., on average 193 flight hours). Study five examined secondary auditory oddball performance, gaze behaviour and flight performance as a function of task condition (single, dual) and flight phase (cruise, landing). Results: Results from the first four studies revealed several uses for traditional (i.e., dwell time, fixation rate, fixation duration, scan path length) and advanced (i.e., SGE, GTE, cognitive tunneling analysis) gaze behaviour metrics. Specifically, when task requirements increased (i.e., sensorimotor demands, cognitive load) the focus of attention became more biased toward areas that held more task-critical information and were necessary for successful task performance. Many of these measures were also sensitive to phase specific changes in gaze behaviour associated with distinct task goals. Indeed, overall shifts in gaze dispersion, dwell time, and scanning patterns were shown to reflect sources of information that were important for achieving flight task specific sub-goals. Such differences were evident independent of changes in sensorimotor difficulty or cognitive load. These changes in gaze behaviour due to variation in task requirements were consistent across low-fidelity and high-fidelity cockpit environments. Several gaze behaviour measures also demonstrated that experienced pilots used vision more efficiently and effectively, by sampling more task-related regions of the environment more frequently with fewer instances of cognitive tunneling. The last aviation study was the only paradigm that did not show significant differences in gaze behaviour or flight performance due to increased cognitive load. This was despite the presence of increased auditory response times and error rates. Although most gaze metrics examined here were modulated (or influenced) by a number of factors impacting skill performance, blink rate seemed to be the one measure that was not consistent. Conclusions: Gaze behaviour analysis provides important spatiotemporal information related to the underlying cognitive processes supporting complex skill performance. Gaze behaviour metrics are sensitive indicators of various task requirements and individual resource availability. It is important to note that the gaze behaviours reported are highly task dependent and are stable across the environmental contexts examined here. Collectively, the gaze metrics examined here provide valuable information for assessing information processing and can contribute to better characterization of visual scanning in complex environments.
The Effects of Deprivation Amblyopia on Fixation Stability and Optokinetic Nystagmus
(University of Waterloo, 2024-06-04) Nasir, Mohad
Vision and oculomotor control play an essential role in visual perception and motor coordination. Individuals born with unilateral cataracts ultimately develop deprivation amblyopia, which is associated with sensory deficits. By measuring two fundamental eye movements, fixation stability and optokinetic nystagmus, this study aims to understand how congenital cataracts impact oculomotor control. Fixation stability and OKN were evaluated using the Eyelink eye tracker during binocular and monocular viewing. An infrared filter was used in the monocular condition to block the visible light (i.e., open loop condition) but allowed recording of eye position. The fixation stability experiment utilized a 3° fixation crosshair, while the OKN test involved a black-and-white vertical square-wave grating moving at 10 deg/s. Eye dispersion during fixation was quantified using bivariate contour ellipse area (BCEA), as well as microsaccades rate, amplitude, and slow drifts. OKN response analysis involved calculating the slow-phase gain based on the velocity of the stimulus, and subsequently determining if the response in the fellow eye was symmetrical across nasalward and temporalward stimulus directions. The findings of 18 control participants showed that fixation stability was best during binocular viewing, as indicated by the lowest BCEA value. Fixation stability was poorer during monocular viewing, where the covered eye (open loop condition) exhibited the largest dispersion. Further data analysis revealed that the poorer fixation during monocular closed-loop viewing was explained by increased microsaccade rate and higher slow drift velocity, while the poorer fixation during the open-loop condition was explained by the increase in microsaccade amplitude. The patient group included 7 participants. The fellow eye had fixation that was similar to the control group across binocular and closed-loop monocular viewing, while it was poorer during monocular viewing for the open-loop condition. Amblyopic eye viewing was poorer compared to all viewing conditions in the control group. The OKN response was asymmetrical for 2 of the patients, with one patient showing no response in the temporalward direction, while all 18 control participants exhibited a symmetrical response that was similar for the nasalward and temporalward trials. This study has provided insight into oculomotor control in unilateral deprivation amblyopia. Further research that investigates the underlying neural mechanisms disrupted in oculomotor control in unilateral deprivation amblyopia can help to uncover more effective treatment options to improve the quality of life and sensorimotor deficits in individuals with deprivation amblyopia.
Examining the effects of a passive upper extremity exoskeleton on shoulder fatigue during a simulated automotive overhead weld inspection task
(University of Waterloo, 2024-04-26) Kurt, Jacklyn
Exoskeletons are emerging as occupational assistive devices, and in particular passive upper extremity exoskeletons have been implemented in workplaces in situations where it is not possible to remove overhead work job elements. Previous studies have commonly reported the effects of exoskeleton usage on the deltoid muscles during short duration tasks, but these data incompletely characterized how exoskeletons may influence shoulder fatigue development and subsequent injury risk. The main purpose of this thesis was to quantify the exoskeleton’s impact on psychophysical, localized muscle, and strength measures of fatigue in the shoulder throughout a two-hour simulated welding task. Ten male participants completed two in-lab sessions of the same task with and without the exoskeleton. Psychophysical measures of exertion, shoulder, elbow, and wrist discomfort were recorded along with surface electromyography (EMG) from bilateral supraspinatus, infraspinatus, upper trapezius, anterior and middle deltoids using a posture-controlled weighted reference task to calculate changes in mean power frequency (MPF) every 10 minutes throughout the 2-hour protocol. Maximum voluntary strength efforts (abduction and external rotation) were completed every 20 minutes to monitor changes in strength. The left and right sides were compared over time to assess potential changes in strategy throughout the task progression. The absence of significant hand by time interactions indicated there was no systematic change in strategy throughout the task protocol. The overhead weld inspection task caused increased markers of fatigue (decreased MPF) in the supraspinatus, infraspinatus, and upper trapezius over the 2-hour protocol. Wearing the exoskeleton resulted in significantly higher MPF compared to no exoskeleton in the supraspinatus (p<0.001), infraspinatus (p<0.001), and upper trapezius (p<0.001), with measures remaining at baseline in the EXO group, indicating a lack of fatigue development. Shoulder discomfort was reduced by 0.67 points (EXO = 1.97, NE = 2.64) when wearing the exoskeleton. Additionally, wrist discomfort was 0.4 points lower without the exoskeleton (EXO = 1.06, NE = 0.66), suggesting that the wrist and other body regions that are not targeted by the exoskeleton should be monitored if these devices are implemented. External rotation force was also lower with the exoskeleton than without, driven by a decrease in force output at the start of the collection period that returned to baseline values by the end of the 2-hour protocol. This could indicate that the exoskeleton may have affected cognitive fatigue in these non-expert users; however, cognitive fatigue was not directly measured in this thesis and should be investigated further in future work. Overall, this thesis provides novel findings regarding the effects of a passive upper extremity exoskeleton on muscular fatigue, particularly in the glenohumeral stabilizing muscles (supraspinatus, infraspinatus, and upper trapezius). This had not been previously explored during an extended duration task representative of the workplace.
The effects of carbonic anhydrase inhibitors on exercise performance in acute hypoxia
(University of Waterloo, 2024-04-24) Chang, Jou-Chung
Acute mountain sickness (AMS) can occur due to rapid altitude ascents and/or insufficient acclimatization. Acetazolamide (AZ) is commonly prescribed for AMS prophylaxis but appears to inhibit exercise performance. Methazolamide (MZ) has similar prophylactic benefits but does not have a similar decrement in isolated small muscle mass exercise in normoxia. We compared whole-body exercise performance in acute hypoxia (FIO2 = 0.15) between AZ and MZ and hypothesized that time trial duration will be the shortest in MZ compared with AZ and placebo (PLA). Fifteen young healthy participants completed 5 testing visits: day 1 maximal exercise test, day 2 a familiarization visit, and Day 3-5 were the experimental visits. Each experimental visit involved a 5-km hypoxic cycling time trial performed after a 2-day dosing protocol of either AZ (250mg t.i.d.), MZ (100mg b.i.d.) or PL (t.i.d.); the order was randomized and double-blinded. Before and after each experimental time trial, capillary blood samples were taken, and maximal voluntary contractions of the quadriceps were performed. AZ and MZ resulted in a partially compensated metabolic acidosis at rest (capillary H+ 47±3, 43±2, 39±2 nmol for AZ, MZ and PLA respectively, p<0.01). Time to complete 5-km on PLA (562±32s, p<0.01) was significantly faster than AZ and MZ (577±38 vs. 581±37s respectively), with no differences between AZ and MZ (p=0.96). The 5-km average ventilatory efficiency (V̇E/V̇CO2) listed from greatest to least was MZ, AZ and PLA (46±6, 43±4, 37±3 respectively) and were all significantly different (p<0.05). There were no differences in the average ventilation (124±27, 127±24, 127±19 L/min respectively) and oxyhemoglobin saturation (87±2, 88±2, 88±3 respectively) between PLA, AZ and MZ (p>0.05). Peak quadricep torque before exercise was found to be significantly lower in AZ compared to PLA and MZ (543± 77, 574± 76, 552± 67 N respectively, p<0.05). In conclusion, both AZ and MZ impaired whole-body exercise performance in acute hypoxia and this finding might be important to consider for high altitude occupations.
Effects of a Single Shift of Occupational Childcare on Knee Mechanics during Gait
(University of Waterloo, 2024-04-16) Peckett, Kimberly
The current literature shows that there are ergonomic challenges in occupational childcare, such as inappropriate heights of furniture for adults, and that childcare educators engage in high knee flexion positions beyond levels that have been previously associated with an increased risk of developing knee osteoarthritis. However, what has not yet been investigated is the possibility that childcare educators’ knee mechanics during everyday activities, such as walking, differ after their shift, likely as a result of their daily work activities and work environment. This study aimed to evaluate the differences in childcare educators’ knee kinematics and kinetics before and after their workday, in gait measures that, when compared to controls, have been associated with knee joint injury and disease, including knee flexion angle at heel strike, peak knee adduction angle, peak knee flexion moment, and peak knee adduction moment during gait. For this study, 21 childcare educators were recruited from early learning centres in the Waterloo/Wellesley areas. In their place of work, before (baseline) and after their workday, each participant completed walking trials until three successful trials, defined as their entire foot contacting the first force plate and the heel of the same foot contacting a second force plate in the same gait cycle, were obtained for each leg. Motion data and ground reaction forces were collected using markerless motion capture cameras and force plates, respectively. Two-tailed paired samples t-tests were run to evaluate changes in all outcome variables for both legs, except for peak adduction moment on the non-dominant leg, which was evaluated using the non-parametric equivalent test (Wilcoxon signed-rank test). There was a statistically significant increase in peak knee flexion moment (p = 0.031) after the shift compared to baseline. No statistically significant pre- to post-shift differences for any other dependent variable on either leg was found (all p > 0.05). Inter-trial error was calculated for the pre-shift gait trials as a measure of the natural variability in the participants’ gait outcome measures. Participants who experienced a change (post minus pre-shift) larger than the inter-trial error can be said to have exhibited a change over their work shift that cannot be explained by natural variability alone. For at least one leg, there were 19 such participants for the kinetic outcomes and 16 such participants for the kinematic outcomes. The results from this study suggest that a single shift of occupational childcare does have an effect on the childcare educators’ knee mechanics during gait.
Occupational Health Research in Workplaces Transitioning from Modernity to Post-Modernity
(University of Waterloo, 2024-04-11) Carlan, Nicolette
Occupational health is a complex concept and the offspring of a marriage between law and science. The marriage is influenced by multiple extended families or networks, which act together and in opposition to create policy and modify work practices (Levenstein &Wooding 1999). The extended families now live in societies that are transitioning from modernity to postmodernity. For the purposes of this paper modernity describes the era when computers and data collection became readily available. Post-modernity describes the era when access to information and its accompanying power provided by that information became universally available because of access to the internet. Research into occupational health has several goals including the identification of risk, the introduction of potential practices to reduce risk, and setting standards for which compensation is awarded. It is my hypothesis that the societal structure influences not only the subject of this research but also the methods of research, the conclusions of researchers and the potential impact of the research. This applied research programme brings together three studies, that focus on musculoskeletal disabilities (MSDs), that have all been conducted during the transitional period from modernity to post-modernity. Each study examines the creation, dissemination and implementation of knowledge - key products of research. In this period of transition, the ability to conduct research is also in transition. Data collection is changing because there are fewer large workforces tied together with large insurance and corporate data bases. There is an increase in contingent work with workers changing work relationships on a regular basis. The economic impact of adverse health outcomes is blurred because insurance coverage is no longer mandatory. In addition, the ability to transfer knowledge is more complex because compulsory training is less common. The first study examines the development of knowledge about MSDs in a workplace that is in the initial stages of transition to post-modernity. The workplace is now primarily staffed by a part-time and transitory workforce, which was not fully engaged in health and safety activities. In this workplace, the union identified greater than expected MSDs but could only identify limited prevention activities. So, the full- time workers took the lead to build a body of knowledge that could be used to reduce injuries in the future. Participatory research methods gave voice to the workers’ experiential knowledge. That knowledge improved the tools promoted by academic researchers which ultimately resulted in a body of knowledge that has the potential to improve work practices. Unfortunately, at the beginning of the process we did not pay enough attention to one of the participating families, the employer, which did not participate or promote changes in work practices. As a result, we cannot report on any specific health and safety improvements. However, we are left with a body of knowledge and a group of workers with the skills to collect data and the ability to continue to promote safer working conditions. The second study looks at the potential adverse health effects resulting from the introduction of new work processes in a non-traditional work setting. In this case the source of potential long-term injuries was identified by the workers. The workers together with an interdisciplinary research team documented adverse health findings. Because the workforce was contingent, the economic benefits which could be attributed to ergonomically beneficial tools were not obvious. As a consequence, the acquisition of better tools was not pursued by the employer/contractors. However, the research team was able to document developing adverse health outcomes that could set the stage for compensation in the future and introduce prevention ideas to the workforce. The final study examines the knowledge creation process in workplaces that are nearing the described characteristics of post-modernity. The stories of workplace parties identified the characteristics of successful innovators and welcoming non-traditional workplaces. A secondary analysis of qualitative interviews shed light on the common characteristics of innovators. That analysis also confirmed the importance of networks to disseminate knowledge with the aid of social capital owned by innovators. We were also able to document the benefit of fluid work demands which allotted time to make mistakes and pursue change. These studies establish that it is necessary to not only to be guided by established research methods but to also be cognizant of the context in which the research is conducted. With modified research methods, the teams were able to collaborate with transitioning workforces to create knowledge about health outcomes, disseminate that knowledge, and set the stage for the application of that knowledge. These studies illustrate that research which can contribute to safer workplaces must accommodate the societal boundaries in which it is conducted.
Multifaceted Approaches to Enhancing Shoulder Health in Breast Cancer Patients undergoing Radiation Therapy: quantification of treatment effects and rib fracture prediction assessment
(University of Waterloo, 2024-04-11) Herrera Valerio, Maria Cristina
Radiotherapy is a highly effective treatment for breast cancer, but it is also associated with several complications that can impact patients’ quality of life and overall survival. This dissertation addressed the lack of research examining the influence of radiation therapy on shoulder health indicators during the treatment window. Additionally, it investigated the effectiveness of an intervention program focused on shoulder strength to compensate for potential shoulder health impairments. Finally, it assessed the feasibility of using quantitative ultrasound for more accessible evaluations of rib fragility fractures, which may arise as a long-term consequence of radiation therapy. Study 1 and 2 shared an in vivo experimental collection. Shoulder health indicators of the affected limb of 27 breast cancer patients were tracked at baseline, midpoint, and endpoint assessments within the radiation therapy window. The activation of latissimus dorsi, teres major, pectoralis major, and serratus anterior, were quantified using a wearable electromyography (EMG) device during two shoulder flexion-extension, two shoulder abduction-adduction, and two shoulder external-internal rotation submaximal tasks. The kinematics of the shoulder complex were measured using an Inertial Measurement Unit (IMU) during six maximal range of motion trials involving flexion, abduction, and external rotation. Additionally, arm strength was evaluated using a hand-held dynamometer during flexion, extension, abduction, adduction, external rotation, and internal rotation maximal exertions. Finally, the arm circumference was determined using a measuring tape. Study 1 showed significant changes (p<0.05) in the latissimus dorsi and teres major muscles during all evaluated shoulder movement tasks. There was also a significant reduction (p<0.05) in shoulder abduction at the end of treatment compared to baseline. No changes were noted in pectoralis major and serratus anterior muscles, nor in arm strength. Radiation dose was negatively correlated with shoulder abduction range of motion. Study 2 evaluated and compared a control group with a shoulder strength intervention group throughout the radiation treatment. The intervention group exhibited higher activation of teres major and serratus anterior compared with control group (p < 0.05) in external- internal rotation and flexion-extension movement tasks. This group also exhibited significantly greater (p<0.05) arm strength and negative correlations between radiation fractions and arm strength for all the evaluated movements. No significant differences were noted in pectoralis major and latissimus dorsi activation, nor shoulder complex range of motion between the groups. Study 3 employed an in-silico approach to simulate oncological treatments and demonstrated that Quantitative Ultrasound Imaging of Bone (QUSIB) is sensitive to the structural changes induced by these therapies. Specifically, two sets of ribs were created to simulate the effects of 5 years of radiation and bisphosphonate treatments. Acoustic attenuation and backscatter coefficient parameters were examined to assess their ability to detect changes in trabecular structure. The results revealed significant correlations (p<0.05) between the observed and predicted values of Bone Volume Fraction (BV/TV). Furthermore, significant differences (p<0.05) were observed in trabecular thickness between the base and simulated radiation and bisphosphonate models. This dissertation provides valuable insights into the effects of radiation therapy on shoulder functionality. It aims to help patients minimize the potential side effects of this treatment and assist health providers in finding more accessible solutions for managing these long-term consequences.
The Role of Sarcolipin in Muscle Adaptation with Aging
(University of Waterloo, 2024-04-08) Chambers, Paige Jilleia
The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pump facilitates the transport of Ca2+ against a concentration gradient from the cytosol to the lumen of the SR, eliciting relaxation and maintaining Ca2+ homeostasis. Sarcolipin (SLN) is a small allosteric regulator of the SERCA, which when bound to the pump, lowers SERCA Ca2+ affinity and reduces SERCA efficiency by uncoupling the Ca2+ transport efforts from ATP hydrolysis. Previous research has revealed that through the regulation of SERCA activity, SLN can alter muscle function, energy expenditure, and promote Ca2+ signalling for metabolism, fibre type and muscle mass. While extensive research has characterized SLN expression and function in young adult male mice, few studies have examined SLN with aging and no studies have reported on SLN in female mice. Therefore, the purpose of this thesis was to examine sex and age-related differences in SLN expression and to discern the role of SLN in altering SERCA function, energy expenditure, and Ca2+ signalling between sexes with aging. The first study, described in Chapter 3, explored sex-specific differences in SLN expression in young adult mice and investigated the consequences of SLN ablation on SERCA function and whole-body energy expenditure in both male and female mice. The study revealed that the soleus muscles of female mice exhibited higher levels of SLN content compared to male counterparts, which was accompanied by greater SERCA efficiency and increased adiposity with SLN ablation in females. This study reported that SLN ablation reduced whole-body energy expenditure in both male and female mice, in the absence of changes to habitual activity levels. Although females displayed relatively greater SLN content than males, the impact of SLN ablation on absolute whole-body energy expenditure was more pronounced in males, likely attributed to their greater lean muscle mass. The second study of this thesis (Chapter 4) had two main aims: first, to investigate sex-related variations in SLN expression with aging, and second, to examine if SLN may offer SERCA protection against age-relative oxidative damage and dysfunction. With respect to the first aim, this study found that SLN expression increased with age and that the sex differences in SLN expression persisted with age, with females displaying greater SLN expression in soleus muscles across age groups. In order to examine the role of SLN in the protection of SERCA with aging, measures of SERCA function and SERCA damage were assessed in the soleus muscles of wild type (WT) and SLN ablated (Sln−/−), male and female mice at two ages, 4-6 months and 18+ months, reflecting young adult and older adults, respectively. Contrary to the hypothesis, SLN ablation had no impact on SERCA nitrosylation with aging and SLN ablation appeared to inhibit SERCA function in a manner similar to young adults. Additionally, the research uncovered sex-specific differences in nitrosylation damage to SERCA1a, with females displaying greater damage to SERCA1a than males. This data challenges the prevailing notion that SERCA2a is more susceptible to age-related oxidative damage, as previous studies have exclusively examined males. The final study (Chapter 5) of this thesis examined whether the upregulation of SLN with aging activated calcineurin (Cn) signalling and promoted greater muscle mass and muscle function. Similar to findings in Chapters 3 and 4, SLN expression was higher in the soleus muscles of both females and older animals compared to male and young adult counterparts. This study aligned with several established sex and age-differences in the literature. Mainly, females and older animals displayed lower muscle mass, absolute force and fewer type II fibres than males and young adult, respectively. In contrast to the hypothesis, SLN ablation had no discernible impact on Cn signaling, muscle mass, or maximal muscle function, suggesting the upregulation of SLN with aging may not serve the same role in promoting beneficial Ca2+ signaling as observed previously in various unloading and disease models. While SLN ablation did not impact Cn signalling, this study revealed novel evidence for the activation of Cn signalling in skeletal muscle with age. This may align with previous research finding elevations to resting cytosolic [Ca2+] in aged muscle and future research should directly target Cn in order to discern the impact on muscle mass, fibre type and function with aging between sexes. The collective results of the studies presented here confirm that SLN expression increases with age in both male and female mice and aids in clarifying the role of SLN in aging muscle. Furthermore, the studies of this thesis sought to begin addressing the sex bias within SLN research and revealed the consistent and novel evidence that SLN expression is greater in females. The sexual dimorphism in SLN expression make the argument for the use of female mice in studies examining SLN and provide foundational evidence for future research examining the impact of SLN on muscle metabolism between sexes.
Characterizing the Roles of Myoregulin and Dwarf Open Reading Frame in Regulating Calcium Homeostasis in Muscle
(University of Waterloo, 2024-01-26) Juracic, Emma Sara
The sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) are responsible for inducing muscle relaxation and are integral to the maintenance of intracellular calcium (Ca2+) homeostasis. As such, their activity is modulated by multiple regulatory proteins. Two well-characterized regulators of SERCAs are the homologous proteins sarcolipin (SLN) and phospholamban (PLN), which act to reduce the pump’s Ca2+ affinity/maximal activity. Though PLN and SLN share structural and functional homology, they exhibit distinct and diverse biological roles. It is well established that through their interaction with the SERCA pumps, both proteins are key regulators of muscle contraction/relaxation and both confer protection to the pump under times of cellular stress. However, SLN but not PLN, increases the amount of energy required by SERCA pumps, making SLN a key modulator of skeletal muscle energy metabolism, and protective against diet-induced obesity. Moreover, SLN plays a critical role in activating calcium signaling pathways that control adaptations in muscle mass and fiber type under conditions of muscle overload, disuse and disease. Myoregulin (MLN) and dwarf open reading frame (DWORF) are newly discovered protein regulators of SERCAs that share extensive sequence homology with SLN and PLN, and physically interact with the pump to regulate Ca2+-handling in muscle. Our understanding of these new regulators is still in its infancy. MLN has been shown to exert an inhibitory role similar to that of PLN and SLN by lowering SERCA Ca2+ affinity. Meanwhile, DWORF has been shown to act as a positive regulator of the pump both by removing the inhibition incurred by SLN, PLN and MLN and by directly stimulating SERCA Ca2+ affinity and/or maximal activity. While MLN and DWORF have emerged as key regulators of Ca2+ homeostasis and muscle contractility, it is unknown whether MLN and DWORF share similar roles to PLN and SLN and/or offer their own distinct and diverse physiological roles. It is well established that SERCAs are highly susceptible to damage and inactivation by high levels of oxidative stress and that their function is commonly impaired under conditions of muscle overload, disuse and disease. Thus, it is imperative to determine whether MLN and DWORF can protect the SERCA pumps from cellular stress. Furthermore, SLN’s ability to uncouple SERCA Ca2+ transport from ATP hydrolysis, and in doing so, alter SERCAs’ Ca2+ transport efficiency, is a vital mechanism underlying energy metabolism in skeletal muscle. Investigating whether MLN and DWORF can also contribute to muscle based adaptive thermogenesis by altering SERCA efficiency could offer new avenues for investigating whole body and muscle based metabolism. Finally, these four regulatory proteins appear to share overlap in their expression patterns, therefore, understanding whether the expression pattern of these two newly discovered proteins is altered by the absence of SLN and/or PLN would offer valuable insight into governance of intracellular Ca2+ homeostasis. To that end, the primary objectives for this thesis were to: 1) investigate whether the interaction between MLN:SERCA and DWORF:SERCA can protect the pump from damage during times of cellular stress, such as the thermal instability caused by heat shock; 2) determine whether MLN and/or DWORF were able to alter SERCA Ca2+ pumping efficiency; and 3) examine the potential compensatory changes in expression by evaluating MLN and DWORF gene and protein expression in Sln-/-, Pln-/-, and Sln-/-/Pln-/- mice. To address the first objective, HEK-293 cells were transfected for cDNA encoding SERCA1a or SERCA2a alone (20 ug) and co-transfected for cDNA encoding SERCA1a or SERCA2a (10 ug) at a molar ratio of 1:1 to those encoding MLN or DWORF (10 ug) with a total plasmid DNA of 20 µg. To induce heat stress (HS), prior to harvesting half of the cells from the groups were exposed to 40°C for one hour (HS) while the other half of the cells remained incubated at 37°C to be used as controls (CTL). Effects of HS on Ca2+-dependent SERCA activity was evaluated on crude cell homogenate over Ca2+ concentrations ranging from pCa 6.85 to 4.80 in the presence of the Ca2+ ionophore A23187 using a Ca2+-dependent, enzyme-linked spectrophotometric plate reader assay. Furthermore, effects of HS on the oxidation and nitrosylation of the SERCA protein were determined by western blotting on crude cell homogenate to assess oxidation by measuring protein carbonyls and nitrosylation by measuring nitrotyrosine formation. HS treatment of cells transfected with SERCA1a and SERCA2a alone significantly reduced maximal activity of both isoforms (p < 0.05) and resulted in stark elevations in both oxidation (p < 0.05) and nitrosylation (p < 0.05) of the pumps compared to CTL. In contrast, exposure of cells co-transfected with SERCA1a and MLN or DWORF and cells co-transfected with SERCA2a and MLN or DWORF to HS maintained maximal activity at levels resembling that of CTL (p > 0.05) and prevented SERCA oxidation (p > 0.05) and nitrosylation (p > 0.05), again keeping levels comparable to CTL. The results of this thesis are indicative of MLN and DWORF stabilizing SERCA structure and function during cellular stress by preserving maximal pump activity of both SERCA isoforms while minimizing oxidation and nitrosylation of the pump in the face of HS. To investigate the second objective, HEK-293 cells were transfected for cDNA encoding SERCA1a or SERCA2a alone (20 ug) and co-transfected for cDNA encoding SERCA1a or SERCA2a (10 ug) at a molar ratio of 1:1 to those encoding MLN or DWORF (10 ug) with a total plasmid DNA of 20 µg. Both Ca2+ uptake and Ca2+-ATPase activity were measured on crude cell homogenate prepared from the transfected cells. Ca2+-dependent SERCA activity was assessed over Ca2+ concentrations ranging from pCa 6.85 to 4.80 in presence and absence of the Ca2+ ionophore A23187 using a spectrophotometric plate reader assay. SERCA-mediated Ca2+ uptake was measured in the presence and absence of the precipitating anion, oxalate, using the fluorescent dye Indo-1 and spectrofluorometric plate reader assay. SERCA coupling ratio was calculated by dividing Ca2+ uptake by Ca2+-ATPase rates across different pCa values. The ionophore ratio was determined at each pCa to provides an additional way of assessing SERCA efficiency and was calculated by dividing SERCA activity measured in the presence of the ionophore by SERCA activity measured in the absence of the ionophore. In both the presence (p < 0.05) and absence of ionophore (p < 0.05), MLN significantly depressed the maximal rate of ATP consumption (Vmax) and SERCA’s Ca2+ affinity. Moreover, in both the presence (p < 0.05) and absence of oxalate (p < 0.05), MLN was shown to reduce SERCA Ca2+ uptake. However, MLN did not affect the Ca2+/ATP coupling ratio of SERCA1a and SERCA2a pumps at maximal (presence of ionophore/oxalate) and physiological (absence of ionophore/oxalate) conditions. Nor did MLN alter the ionophore ratio at each pCa. Thus, MLN does not have a bearing on SERCA pumping efficiency and is unlikely to contribute to muscle based energy expenditure. When examined in both the presence (p > 0.05) and absence (p > 0.05) of a Ca2+ gradient, DWORF had no bearing on the apparent affinity of SERCA1a and SERCA2a for Ca2+, no effect on maximal SERCA activity, no impact on the rate of SERCA-mediated Ca2+ uptake and did not alter the apparent coupling ratio or ionophore ratio, as no difference was observed between cells transfected with SERCA1a alone and those co-transfected with SERCA1a and DWORF or for cells transfected with SERCA2a alone and those co-transfected with SERCA2a and DWORF for any of these measures. Furthermore, no significant differences in Ca2+ affinity and maximal activity were observed in cells that were transfected with either SERCA isoform alone or co-transfected with DWORF (1:3) in either maximal (p > 0.05) or physiological (p > 0.05) conditions. Interestingly, DWORF was shown to increase SERCA apparent affinity for Ca2+, maximal SERCA activity and the rate of SERCA-mediated Ca2+ uptake in both the presence (p < 0.05) and absence (p < 0.05) of a Ca2+ gradient in cells co-transfected with SERCA1a or SERCA2a and DWORF at a molar ratio of 1:5. However, despite the activation of SERCA observed with a five-fold overexpression of DWORF, the apparent coupling ratio and ionophore ratio remained unaltered, therefore indicating that DWORF does not influence SERCA pumping efficiency. Lastly, to evaluate the third objective, western blotting was performed on soleus, left ventricle and atrial muscle isolated from 4-6-month-old male and female wild type mice and compared to single knockout (Sln-/- and Pln-/-) mice and double knockout (Sln-/-/Pln-/-) mice to examine if ablation of one or two SERCA regulatory protein(s) would result in compensatory changes in the expression of other SERCA regulatory proteins. In the Pln-/- genotype, no change in MLN or DWORF protein expression was detected with the ablation of PLN in both soleus (p > 0.05) and left ventricle (p > 0.05) muscle in either male nor female mice. Likewise, the Sln-/- genotype revealed no change in MLN or DWORF protein expression in the absence of SLN in both soleus (p > 0.05) and atrial (p > 0.05) muscle in either sex. Similarly, in the Sln-/-/Pln-/- model, the results for both proteins in both sexes matched what was observed in the single knockout models, as the ablation of both SLN and PLN did not result in any significant changes in the expression of MLN and DWORF (p > 0.05). To compliment the protein expression analysis, real-time PCR (qPCR) was performed on SOL and LV muscles from the same WT and knockout male and female mice to investigate potential changes in Mln and Dworf gene expression in the presence and absence of Sln and Pln expression individually and dual ablation. Gene expression of Mln was only altered in left ventricle tissue of female DKO, showing an elevation relative to WT (p < 0.05). The change in gene expression was generally unaltered in skeletal muscle tissue, with only soleus of male Sln-/- mice showing a significant elevation in Dworf expression (p < 0.05). In contrast, cardiac tissue exhibited a more complicated story: left ventricle tissue of male and female Pln-/- mice showed either a trending increase (p > 0.05) or significant increase (p < 0.05), respectively. Similarly, atria of Sln-/- male mice exhibited a trending increase in Dworf expression (p > 0.05), whereas, atria of Sln-/- female mice exhibited a significant decrease (p < 0.05). Finally, left ventricle and atrial tissue of both male and female Sln-/-/Pln-/- mice displayed a significant decline in Dworf expression (p < 0.05). Overall, this thesis has revealed that i) similar to SLN and PLN, MLN and DWORF stabilize SERCA structure and function during cellular stress; ii) like PLN, MLN negatively regulates SERCA kinetics without altering transport efficiency; iii) unlike any other known regulator, DWORF positively modulates the pump by enhancing SERCA apparent Ca2+ affinity, maximal activity and the rate of Ca2+ uptake without changing SERCA pumping efficiency; and iv) under basal conditions, the protein expression levels of MLN and DWORF are not altered by the presence/absence of either PLN and SLN alone or the presence/absence of both PLN and SLN together.
Cardiac motion simulation in cadavers and carotid artery longitudinal wall behaviour
(University of Waterloo, 2023-12-21) Stevens, Kailey
Carotid artery longitudinal motion (CALM) is a bidirectional, multiphasic motion of the intima-media complex of the common carotid artery (CCA) wall. This motion has exhibited changes with aging, elevated cardiovascular disease risk, and various diseased conditions. Understanding the determinants of this motion may position CALM as a diagnostic tool for arterial health. Retrograde wall displacement is the hallmark feature of this phenomenon and represents movement of the arterial wall in the opposite direction of blood flow, but its etiology remains undiscovered. While retrograde motion has been proposed to result from cardiac contraction due to ventricular-vascular coupling of the arterial tree and the heart, separating hemodynamic influences from cardiac contraction is not possible in vivo. This study explores simulated cardiac contraction in cadavers and the influence of longitudinal prestretch and material stiffness on carotid artery longitudinal wall behavior. Eight cadavers (5 males, 85 ± 7 years (n = 7) in addition to one 19-year-old donor (n = 1)) underwent a dissection and tissue testing protocol. The dissection protocol examined the relationship between caudal force application at the ascending aorta and resulting CCA longitudinal wall displacement. A repeated measures correlation revealed a moderate negative correlation for applied force and wall displacement (r = -0.68, p < 0.001, 95%CI [-0.76, -0.60]). Displacement was estimated for a standardized force of 6 N for each donor and artery. Longitudinal prestretch did not influence displacement at 6 N (rLCCA = -0.13, p = 0.78; rRCCA = -0.63, p = 0.13). There was no significant relationship found between displacement at 6 N and either longitudinal strain [rLCCA = -0.72, p = 0.070; rRCCA = -0.27, p = 0.56] or elastic modulus at 35 kPa [rLCCA = 0.50, p = 0.25; rRCCA = 0.29, p = 0.53] for either side. Circumferential strain [rLCCA = -0.068, p = 0.14; rRCCA = 0.13, p = 0.79] and elastic modulus [rLCCA = 0.58, p = 0.23; rRCCA = -0.31, p = 0.50] were not related with displacement at 6 N for either side. Differences between the LCCA and RCCA were identified for the slope of force-displacement line of best fit [p = 0.0347, Cohen’s d = 1.17, n = 6], longitudinal strain at 35 kPa [p = 0.020, Cohen’s d = 1.37, n = 6], and circumferential elastic modulus at 35 kPa [p = 0.018, Cohen’s d = 1.72, n = 5], suggesting increased wall displacement in the LCCA and increased stiffness of the RCCA. Our findings suggest that cardiac contraction is a primary determinant of CALM, and cardiac imaging should be conducted with CALM imaging in future studies to contextualize differences in motion between individuals and across acute interventions. Due to anatomical branching differences, images should be taken on the LCCA for a more direct influence from cardiac contraction. Our results support the ventricular-vascular coupling theory for retrograde motion in CALM and demonstrate greater wall displacement in the LCCA compared to the RCCA.
Use of a probabilistic model to explore the hip fracture and health economic outcomes of safety flooring implemented in an Ontario retirement home environment
(University of Waterloo, 2023-12-21) Shade, Mikail
Hip fractures suffered by older adults are a serious public health concern. The direct yearly expenditure for hip fractures exceeds one billion dollars in Canada and with the older adult population expected to increase within the upcoming years, this issue will become more significant. Hip fractures therefore require consistent, structured investigations into their mechanism, and any insight which could mitigate the challenges associated with their occurrence, should be actively pursued. Hip fracture investigations frequently employ the factor of risk principle which posits that a hip fracture occurs when the loads applied to the hip exceed the strength of the bone. Appropriately designed safety flooring reduces fall-related impact forces and should theoretically reduce hip fracture risk, however, when implemented into an older adult setting the expected reduction in hip fracture risk is not observed. Yet still economic evaluations of safety flooring suggest that it is a better alternative than standard flooring, supporting its inclusion into older adult settings. Mathematical modelling provides a cost-effective, non-invasive, investigative tool which can be used in tandem with experimental and observational approaches to consider hip fracture risk. A previous model unified experimental and observational data to simulate a population of Canadian older adults, subsequently quantifying their hip fracture risk using the factor or risk principle. However, the simulated population may not be representative of distinct subsets of the Canadian older adult population. Additionally, the model can only assess hip fracture risk in two unique conditions: when the entire population falls on safety flooring, or the entire population falls on standard flooring. These limitations reduce confidence in the model’s ability to quantify hip fracture risk for arbitrary populations and reduce the model’s ability to replicate situations which are objectively more feasible to recreate in the real-world. The objectives of this thesis were to expand the capabilities of the pre-existing probabilistic model, increase its real-world utility by integrating components to simulate specific subpopulations of older adults, incorporate the probabilities of falls in different locations, and consider the economics of implementing safety flooring in specific locations within residential care facilities. The modified probabilistic model supports the notion of population-specific/population-dependent investigations. It also reaffirms the accuracy of understood model assumptions by exhibiting similar behaviours across different populations. Additionally, the model successfully integrated fall location probabilities from observational data to highlight an effect of sex and location on hip fracture risk. Finally, the model suggests that both savings and decisions to implement safety flooring may depend not only on the location of falls but sex characteristics as well. Ultimately, this thesis demonstrates the feasibility of coupling mechanics, epidemiology, and health economics perspectives within a simulation tool to explore the effects of a safety flooring intervention on hip fracture risk in a retirement home setting on older adult hip fracture risk. The outcomes of this thesis may assist decision-makers within multiple industries (residential care facilities, flooring manufacturers, government policy makers) in developing funding policies, priorities, and design decisions.
Characterizing a Novel Enzyme Involved in Cardiolipin Remodelling
(University of Waterloo, 2023-12-05) Hashemi, Ashkan
Background: Cardiolipin (CL) is a specialized dimeric phospholipid comprising approximately 25% of total phospholipids in the inner mitochondrial membrane in eukaryotes, where it functions in energy metabolism, autophagy and apoptosis, and other important cellular processes. CL produced de-novo in the Kennedy pathway is considered nascent due to its non-specific acyl chain profile and is then remodeled to mature CL in the Lands pathway. CL plays several important roles within the mitochondria, including interacting with the electron transport complexes, maintaining the cristae architecture, mediating the apoptotic process, as well as acting in the initiation of mitophagy. Due to these reasons, the appropriate synthesis and remodelling of CL has implications for healthy physiological function. We have discovered a potential novel enzyme involved in CL metabolism, and the purpose of this thesis was to characterize the function of this enzyme in these processes. Major Aims and Approach: The major aims of this thesis were: 1) To investigate the in vitro effects of this enzyme on CL synthesis and 2) To characterize the role of this enzyme in normal physiology using mice deficient in this gene. Results: For our first aim, we discovered that overexpressing this enzyme in HEK-293 cells caused alterations in CL levels in vitro, while the partially purified enzyme displayed an ability to directly remodel monolysocardilipin using phosphatidylcholine as an acyl donor in vitro, which indicates a new and previously unreported function for this enzyme. My second aim had three objectives. The first was to assess alterations in CL content in tissues of mice deficient in this enzyme, versus Wt controls, and we discovered that gene ablated mice displayed tissue-specific alterations in CL content, and this was present in both male and female mice deficient in this enzyme. The second objective was to determine if there are differences in growth, food intake, and gross morphology between wildtype and gene ablated mice. Male gene-deficient mice exhibited differences in food intake, organ weights, and life span. These differences were not observed in female mice, though they followed similar trends despite not reaching statistical significance. The final objective of this thesis was to assess metabolic measures and exercise tolerance. Deficiency in this enzyme caused differences in oxygen consumption, carbon dioxide production, and energy expenditure in both sexes. Male gene-ablated mice also exhibited differences in rearing activity, and exercise tolerance. The differences in rearing activity and exercise tolerance were however not observed in female gene deficient mice. Conclusions: The findings of this thesis indicate a novel role for this enzyme in CL metabolism, including an ability to remodel CL in vitro. Characterization of gene-deficient mice also indicated significant phenotypic differences, especially in male mice, while gas chromatography analysis demonstrated major tissue-specific changes in CL content. These results provide insight into the function of this enzyme.

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