Kinesiology and Health Sciences

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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.

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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.
Does sex influence the effect of mixed mode exercise training on glycemic control, insulin sensitivity and inflammatory markers in overweight/obese, sedentary males and females?
(University of Waterloo, 2023-09-26) Surdi, Julian
Introduction: Type 2 diabetes mellitus (T2D) is prevalent within Canada, with a prediction of 5 million people living with this condition by 2025. Exercise reduces the risk of T2D by improving insulin sensitivity. However, recent trials have suggested that exercise training may be less efficacious at improving insulin sensitivity in females compared with males, which could have implications for the prevention and management of T2D in females. The purpose of this research was to examine whether sex influenced the effectiveness of mixed-mode training on glycemic control, insulin sensitivity and inflammation in overweight/obese individuals. Methods: Twenty-seven overweight/obese, sedentary males (n=12) and females (n=15) were recruited for a 12-week mixed-mode, exercise intervention. Prior to training, participants underwent anthropometric, aerobic fitness (V̇O2max test), strength (3-5 RM test) and oral glucose tolerance test (OGTT) assessments. Training consisted of 3 weekly sessions involving 30 minutes of aerobic and 30 minutes of resistance training. Results: There was no sex difference in glucose AUC (p=0.22, ηp2=0.03) or Cmax (p=0.14, ηp2=0.03); however, when adjusted for the glucose dose relative to LBM, males had a higher glucose AUC (p=0.002, ηp2=0.18) and Cmax (p=0.001, ηp2=0.19) than females. TNF-α, (p=0.04, ηp2=0.13) and MIP-1β (p=0.006, ηp2=0.20) were higher in males than females. There was no effect of training on glycemic control, insulin resistance/sensitivity indices, pancreatic β-cell function or inflammatory markers. However, the absolute change in glucose AUC (males: -99.8 mmol/L·120min, females +58.3 mmol/L·120min, p=0.01, d=1.06), Cmax (males: -0.60 mmol/L, females +0.7 mmol/L, p=0.04, d=0.87) and IL-1ra (males: -18.2 pg/mL, females +28.9 pg/mL, p=0.02, d=1.20) differed between the sexes. . Conclusion: Changes in glycemic control and inflammation following training differed between males and females. A sex difference was seen in inflammatory markers; however, further research is required. Finally, females had lower glucose AUC and Cmax relative to LBM compared to males, which questions the use of a standard 75g glucose dose during an OGTT as a measure of impaired glucose tolerance.
Effects of Heat Stress on HSP70, Sarcolipin, and Phospholamban Content and SERCA Function in Female and Male Rat Skeletal Muscle
(University of Waterloo, 2023-09-25) Brahmbhatt, Aditya
Regulation of cytosolic calcium (Ca2+) levels in muscle is vital to the health and function of muscle due to its involvement in various signaling pathways and cell functions. Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) pumps are found on the membrane of the sarcoplasmic reticulum (SR) and function to actively transport Ca2+ from the cytosol into the SR. Previous work has shown that in the face of heat stress (HS), a model for oxidative stress, heat shock protein 70 (Hsp70) expression is induced to protect the cytosolic domain and function of SERCA. Having previously found that, sarcolipin (SLN) and phospholamban (PLN), which regulate SERCA in the transmembrane (TM) region of the pump, can also preserve SERCA function using both in-vitro and ex-vivo HS models we wanted to assess if they can be stress-induced proteins like Hsp70. The purpose of this project was to assess the sex differences in basal protein expression of Hsp70, SLN, and PLN and the effect of in-vivo heat stress on SERCA function, total protein nitrosylation status, and gene and protein time-course expression pattern of the three proteins in male and female rat soleus and white gastrocnemius (WG) muscles. The heat stress protocol involved submerging the lower limbs of the animals either in a 37ºC (control) or 42-42.5ºC (HS) water bath to either maintain core temperature at 37ºC (control) or between 41-41.5ºC for 30 mins and were either allowed no recovery or were allowed to recover for 24 or 48 hours. Analysis of basal expression found that i) Hsp70 gene expression was higher in both muscles in the females, but its protein levels were higher in the male soleus, ii) SLN gene expression was also higher in both muscles in the females, but no sex differences were observed in the protein levels, and iii) PLN protein expression was higher in the male soleus. In-vivo heat stress i) did not affect SR Ca2+ uptake in the solei of both sexes whereas, in the WG, SR Ca2+ uptake was increased after 24 hours in both sexes ii) did not have an effect on the protein nitrosylation status in the soleus of male and female rats and on WG of female rats, iii) induced both gene and protein expression of Hsp70 in the soleus and WG of both male and female rats, iv) induced protein expression of SLN in the male soleus but only gene expression of Sln in the male WG whereas the same effects were not observed in the females and v) did not induce Pln gene expression in either muscle, but did induce PLN protein expression only in the WG of males. The findings from this study show that even with a relatively mild acute stress model like the one used here, both SLN and PLN were upregulated at least in one muscle of males, indicating that these proteins may also function as stress-induced proteins.
Effects of shoe midsole cushioning on low back impact shock attenuation in recreational runners
(University of Waterloo, 2023-09-22) Fok, Donna
Running is one of the most widely practiced and accessible forms of physical activity. When the foot contacts the ground during running, impacts on the order of two to three times body weight are generated. The impact force is attenuated by joints and propagated through each subsequent segment from the foot to the head over 600 times per kilometer and has been associated with the development of various pains and injuries across runners. Consequently, mechanisms of shock attenuation have been widely researched across the last few decades, where previous work has aimed to examine how joint positioning, eccentric muscle activation, passive soft tissue structures, and other strategies may help mitigate this impact on the musculoskeletal system. However, how these mechanisms are presented in the lumbar spine, which largely influence the delivery and experience of this impact shock in the upper body and head, is not well understood. Further complicating this area is the role of running shoe cushioning, or the midsole. Softer and thicker midsoles have been shown to interact with lower limb kinematics and muscle activation, contributing to differences in leg stiffness and shock attenuation. Therefore, it was hypothesized that more compliant midsoles would produce similar results in the lumbar spine. Specifically, the purpose of this study was to investigate if increased shock transmission and shock attenuation occurred in the lumbar spine in response to softer midsoles. It was further hypothesized that differences would exist in sagittal knee and lumbar flexion angles and trunk muscle activation across midsole cushioning stiffness as well as between sex. Twenty (10M, 10F) pain-free recreational runners who averaged a minimum weekly mileage of 16 km were recruited to participate in this study. Subjects were asked to run on a treadmill at 3.3 m/s for five minutes in each of three shoe conditions that ranged in their midsole cushioning stiffness, quantified prior to use in running via a mechanical testing system. Sagittal kinematics of the lumbar spine, pelvis, and right lower limb were collected using an active motion capture system, mean bilateral muscle activity, co-activation indices, and phase lags between co-activation of the lumbar erector spinae, rectus abdominus, and external obliques were measured via surface electromyography, and accelerometers were placed at the distal tibia, borders of the lumbar spine, and head to calculate peak resultant acceleration as well as shock attenuation in the frequency domain. All variables were calculated during stance phase and averaged across fifteen consecutive strides. Two-way mixed measures analyses of variances were used to assess differences across shoe conditions and between sexes. Softer and more compliant midsoles resulted in increased ankle plantarflexion and knee extension leading to differences in low frequency shock attenuation, but the low back was not particularly responsive to midsole stiffness. Similar tibial and lumbar spine acceleration magnitudes were observed across all midsole stiffness conditions, and neither lumbar posture nor trunk muscle activation and co-activation changed with footwear. Minor differences were observed between sex, suggesting that females may employ slightly different shock attenuation mechanisms particularly at the hips and lower limbs, but future investigations are necessary to better understand the specific shock attenuation mechanisms involved. Overall, these results add to the evidence that midsole cushioning stiffness may influence the lower limb but suggest that such changes are accommodated by the time the shock reaches the lumbar spine.
Characterizing the dynamics of vestibular reflex gain modulation using balance-relevant sensory conflict
(University of Waterloo, 2023-09-21) Goar, Megan
Electrical vestibular stimulation (EVS) can be used to evoke reflexive body sways as a probe of vestibular control of balance. However, EVS introduces sensory conflict by decoupling vestibular input from actual body motion, prompting the central nervous system (CNS) to potentially perceive vestibular signals as less reliable. In contrast, light touch reduces sway by providing reliable feedback about body motion and spatial orientation. The juxtaposition of reliable and unreliable sensory cues enables exploration of multisensory integration during balance control. I hypothesized that when light touch is available, coherence and gain between EVS input and center of pressure (CoP) output would decrease as the CNS reduces the weighting of vestibular cues. Additionally, I hypothesized that the CNS would require less than 0.5 seconds to adjust weighting of sensory cues upon introduction or removal of light touch. In two experiments, participants stood as still as possible while receiving continuous stochastic EVS (with a frequency of 0-25 Hz, amplitude of ± 4 mA, and a duration of 200-300 seconds), while either: lightly touching a load cell (<2 N); holding their hand above a load cell; or intermittently switching between touching and not touching the load cell. Anterior-posterior (AP) CoP and linear accelerations from body-worn accelerometers were collected to calculate the root mean square (RMS) of AP CoP, as well as the coherence and gain between EVS input and AP CoP or acceleration outputs. Light touch led to a decrease in CoP RMS (mean 49% decrease) with and without EVS. Significant coherence between EVS and AP CoP was observed between 0.5 Hz and 24 Hz in the NO TOUCH condition, and between 0.5 Hz and 30 Hz in the TOUCH condition, with TOUCH having significantly greater coherence from 11 to 30 Hz. Opposite to coherence, EVS-AP CoP gain decreased in the TOUCH condition between 0.5-8 Hz (mean decrease 63%). Among the available acceleration data, only the head exhibited a significant increase in coherence above 10 Hz in the TOUCH condition, compared to the NO TOUCH condition. Light touch reduced CoP displacement, but increased variation in the CoP signal that can be explained by EVS input. Light touch may cause the CNS to attribute EVS signals to head movements and therefore up-weight vestibulocollic responses while downweighting vestibulospinal balance responses. Changes in coherence and gain started before the transition to the NO TOUCH condition and after the transition to the TOUCH condition. The loss of sensory information may be more destabilizing than addition, necessitating anticipatory adjustments. These findings demonstrate the ability of one sensory modality to modulate the utilization of another by the CNS, and highlight asymmetries in the timing of responses to the introduction and removal of sensory information, which may impact behavior. 
Sex-based differences in IMCL storage and utilization during an acute bout of high intensity interval exercise (HIIE)
(University of Waterloo, 2023-09-21) Lo, Megan Madeleine
INTRODUCTION: The contribution of lipids, particularly intramyocellular lipids (IMCL), to energy production during high intensity interval exercise (HIIE) is not well characterized. Sex influences lipid utilization during moderate intensity aerobic exercise and thus there may be differences in lipid utilization during HIIE as well. There is conflicting evidence as to whether there is a sex difference in IMCL utilization during exercise, which may be a result of improper matching, differences in methodology, or differential use in subcellular regions. PURPOSE: Our study aimed to determine whether IMCL are used during a bout of HIIE and whether sex influences the extent of IMCL utilization. We also examined whether sex or exercise influenced IMCL storage characteristics and morphology. METHODS: Young, healthy, recreationally active males (n=12) and females (n=12) were matched for aerobic fitness (mL O2• kgFFM-1) and performed an acute bout of HIIE (5 min warm up/cooldown @50W, 10 x 1-min @90% HRmax). Biopsies were collected from the vastus lateralis prior to and following exercise for electron microscopic determination of IMCL storage and western blot analysis of proteins related to lipid and aerobic metabolism RESULTS: Carbohydrate oxidation (p<0.0001) and the increase in blood lactate (p=0.02) were greater in males than females during HIIE, with no difference in fat oxidation (p=0.98). Sex had no effect on content of any proteins analyzed (all p>0.08) or on IMCL area density (all p>0.31). IMCL area density did not change during exercise (all p>0.37) and there was no difference in utilization between the sexes (all p>0.47).IMCL feret (p<0.001), perimeter (p<0.004)and average length of IMCL-mitochondria apposition (all p<0.03) were greater in males. IMCL number (p<0.03) and perimeter to area ratio (p<0.006) were greater in females. CONCLUSION: Fat and IMCL are not significant contributors to energy production during HIIE. Comparable rates of fat oxidation and a lesser increase in blood lactate in females suggest that females relied on anaerobic glycolysis to a lesser extent. Excitingly, our region-specific characterization of IMCL morphology establishes a basis for sex-difference investigation into IMCL storage characteristics.
Long-term effects of concussion: Investigating the relationship between sensory gating and motor learning
(University of Waterloo, 2023-09-14) Walach-Gosse, Kayla
Motor learning relies on the sensorimotor system to interpret, adapt, and integrate sensory inputs to guide motor behavior. A key tenet of the somatosensory system is the ability to inhibit irrelevant information from the CNS to protect higher cortical areas from information overload (sensory gating). Movement and attention can contribute to this process through movement-related gating and relevancy-based facilitation, respectively. Sensory gating occurs at early cortical processing stages and has been shown to be impacted in individuals with a history of concussion. Past work from our lab found a delay in relevancy-based facilitation in a group with a history of concussion compared to healthy controls. The current work aimed to understand the behavioral manifestations that result from disruptions to relevancy-based gating modulations at early cortical processing stages in the concussion population. A total of 40 participants were recruited to participate in this study with 25 in the concussion history group (Hx) and 15 in the control group (No-Hx). This study consisted of 2 experimental sessions that occurred 24 hours apart. During session 1, somatosensory-evoked potentials (SEPs) were elicited via median nerve stimulation while subjects performed a task that manipulated their focus of attention toward or away from proprioceptive feedback. Subjects then completed an implicit motor sequence learning task relying solely on proprioceptive cues. Individuals performed a retention test at session 2, followed by a visual attentional blink (AB) task. The AB is a phenomenon elicited by the rapid presentation of sequential targets which results in reduced accuracy of detecting the second target at the expense of detecting the first target. The No-Hx performed the implicit learning task at session 1 and a retention test at session 2 because SEP and AB data were compared to control data previously collected by this lab. SEP data replicated past work showing an absence of relevancy-based facilitation at early cortical processing stages (N20-P27) that emerged at later processing stages. Our Hx showed evidence of relevancy-based facilitation at either the P50-N70 or the N70-P100 consistent with past work that found this to occur at the N70-P100. Performance on the learning task was not significantly different between the Hx and No-Hx. Performance on the AB task revealed greater AB magnitude in the Hx compared to the No-Hx. Collectively, these results suggest a compensatory strategy in the Hx that enables them to learn to the same degree as controls. However, when the attentional system is taxed with high temporal demands there are decrements in performance. These results are of particular importance given that these individuals are at an increased risk of sustaining subsequent concussions, and musculoskeletal injuries.
Individuality in balance control: Using conventional analytical & machine learning approaches to reveal person-specific differences in standing balance control.
(University of Waterloo, 2023-08-31) Mangan, Gary
The balance control system ensures that humans can perform tasks in a variety of postures despite bipedal stance being inherently unstable. It manages this instability by producing motor outputs that are appropriate to sensory input given the objective of maintaining balance. An inability to maintain this balance may result in a fall which can have both short and long-term physical, psychological, and social effects. The ability to maintain balance is a strong predictor of fall-risk and mobility limitations. Falling has been associated with specific populations such as older adults and those with neurological and neuromuscular pathologies. However, it is possible that some younger individuals may have poor balance control which places them at a greater fall-risk in the face of age and pathology-related influences. The potential importance of revealing person-specific differences in balance control in healthy, young adults has led to the focus of this thesis. This thesis was designed to determine whether a healthy, young adult’s balance control system, as measured by their balance performance, is specific to the individual and could be distinguished from any other individual. The thesis explores the use of different methods of measuring of body movement (kinetic or kinematic), and the analytical techniques which, when collectively applied, may more sensitively reveal these individual differences. General methodology consisted of sixty-one healthy, young adults (ages 18-35), free of any neurological or neuromuscular disorders, performing a series of static standing balance trials. Four task conditions, Base of Support (standard and narrow) and Vision (open and closed), were performed five times, each for thirty seconds. Balance performance was measured kinetically using two floor-mounted force plates, and kinematically using three inertial measurement units placed on the head, sternum, and lumbar region of the back. The resulting data became the substrate for the analyses used in the three studies. Study 1 quantified the consistency of an individual’s balance performance across task conditions relative to the other individuals. Centre-of-pressure data collected from force plates was analyzed using established linear and non-linear analytical methods within the time- and frequency-domains and then input into a linear mixed-effects model. Subject-specific factors, such as anthropometrics and vision quality, were controlled to reduce the number of confounding variables. Correlational analysis of the random-effect, participant, revealed moderate to strong correlations of individual balance performances across task conditions with the strength of these correlations dependent on the analytical technique used. Study 1 confirmed that (1) task-related differences in balance performance could be detected by a variety of analytical techniques, and that (2) the correlations found in relative balance performance across task conditions suggest that an individuals’ balance control system may be specific to the individual. Study 2 expanded on Study 1 by representing body movement kinematically using body-worn inertial measurement units. Similar analytical approaches were used and moderate to excellent correlations in relative balance performance across task conditions were observed. The use of kinematic data in this study also revealed kinematic strategies that could only be obtained by modelling a person as a multi-link, rigid body and not as a single-link, inverted pendulum; an assumption commonly made when using kinetic data. Like Study 1, this work demonstrated that relative balance performance within persons were comparable across tasks of varying difficulty and, as such, indirectly supports the idea that balance control that may be specific to the individual. Study 3 focused on analytical approaches that could more directly reveal the unique features of balance control within individuals. This study employed a machine-learning, classification algorithm in an attempt to identify individuals by their balance performance using kinetic or kinematic measures. Once provided with the prototypical balance performances of a discrete number of individuals, the algorithm was able to correctly attribute the balance performance of a mystery person to one of those individuals with an accuracy greater that what could be achieved by random chance. Representing body movement with kinetic, time-series data yielded the highest accuracies (Accuracy (nway = 5) = 92.08%; Accuracy (nway = 20) = 74.69%). However, it is believed that if kinematic data was recorded with more fidelity, then even greater accuracies could be possible. Study 3 demonstrated that (1) balance performance data contains features specific to the individual which may quantitatively indicate individuality in the balance control system, and (2) that the ability to reveal this individuality is dependent on how the balance performance is represented. This thesis provided two main contributions, (1) support for the idea that balance control during quiet standing, as revealed through balance performance, contains features that are specific to the individual, and (2) an, outline, albeit preliminary, of the task conditions, methods of measurement, and analytical techniques best suited to reveal this individuality.
Characterizing the Biomechanical Exposures Associated with Common and High Demand Personal Support Worker Tasks
(University of Waterloo, 2023-08-31) Ho, Daphne
Background: The physical demands that personal support workers (PSWs) are exposed to are increasing as our population ages and our society is increasingly shifting to at-home care, resulting in increases in workload demands. However, PSWs are also developing high rates of musculoskeletal disorders (MSD) likely because of increased exposure to physical task demands. There is a need to intervene to protect these essential healthcare workers. Presently, little is known about the biomechanical exposure characteristics associated with PSW work tasks, especially within a home care setting. PSW work is highly dynamic and a wide range of tasks with different loading scenarios are completed. This means that the time-series exposure patterns are also likely varied over a work shift or work week, where this variation may be important when designing effective ergonomic interventions. As an example intervention strategy, workload management may be an effective approach to monitor, assess, and redistribute workload as needed to provide recovery windows to reduce and mitigate the accumulation of exposure. Real-time tracking and the continuous monitoring of PSW exposures, or surrogates, may assist in the assessment of injury risk. To better understand the biomechanical exposure characteristics associated with common PSW work tasks and to explore the potential utility of ratings of perceived exertion (RPE) as a potential surrogate measure to track PSW workload, this thesis aimed to address the following two objectives and corresponding research questions: Objectives: 1. Characterize biomechanical exposure metrics associated with the performance of common and highly demanding PSW work tasks. 2. Evaluate the relationship between RPE and the biomechanical exposure metrics. Research Questions: 1. What are the biomechanical exposures experienced by PSWs when performing simulated common and physically demanding work tasks? 2. What is the relationship between RPE and biomechanical exposure metrics (peak low back flexion angle, peak low back extensor moment, cumulative low back extensor moment) when performing common and physically demanding PSW work tasks? Methods: Twenty PSWs were recruited to complete 12 work tasks within a laboratory setting, where full body kinematics and hand forces were collected for all trials. A whole-body top-down rigid link modelling approach was used to calculate biomechanical exposure metrics. Peak low back flexion angle along with peak and cumulative extensor moments were calculated. Linear regressions tested for relationships between post-task RPE scores and 1) peak low back angles, 2) peak low back extensor moment, and 3) cumulative low back extensor moment at an individual level, where corresponding regression statistics from each participant were the aggregated at the group level. Results: Patient handling tasks, such as transfers and repositioning tasks, had the highest peak extensor moments (ranging from 115-157 Nm), while having the lowest cumulative moment values (1329 – 4552 Nm*s). In contrast, patient care tasks such as bathing, dressing/undressing, and compression stocking application, had the highest cumulative extensor moment values (2623 – 8089 Nm*s) and lower peak moments (92 – 107 Nm). Additionally, patient care tasks took the longest to complete and required participants to frequently adopt moderate (20-45 degrees) to severe (>45 degrees) levels of low back flexion. A significant moderate positive relationship was found between RPE scores and cumulative low back extensor moment (p<0.05, R=0.60). No significant relationship was found between RPE scores and both peak low back flexion angle (p<0.05, R=0.16) and peak low back extensor moment (p<0.05, R=-0.13). Discussion: The biomechanical exposure characteristics of PSW work are task dependent. Patient handling tasks subjected PSWs to high peak loads for brief periods of time. Patient care tasks, on the other hand, imposed lower magnitudes of loading for extended time duration. It is well established that low back injury pathways are different when loading is high, but brief, relative to lower in magnitude, but sustained. As such, it appears that groupings of tasks may be of more interest to consider and intervene from the perspective of reducing high peak loads, where others might be better viewed from a cumulative load perspective. Therefore, in the design and development of any effective ergonomic interventions, it may be important to consider task-specific loading profiles and how they may influence injury development based on corresponding pathways. Task characterization as quantified within the current study can serve as a foundation to inform workflow management and patient scheduling decisions in an attempt to optimize temporal aspects of loading. RPE scores could be used as a surrogate for cumulative low back extensor moment, which may have utility as an easy-to-implement assessment tool to track the accumulation of spine extensor moment loading. These findings can inform additional work to evaluate how real-time RPE tracking functions within real work settings and can explore other metrics that might help to better monitor and track exposures during short duration, high load tasks.
The Use of Shear Wave Elastography to Estimate the Mechanical Properties of the Soft Tissues Surrounding the Proximal Femur
(University of Waterloo, 2023-08-28) Bhullar, Sukirat
Introduction: Falls are the leading cause of injury, morbidity, and mortality amongst older adults nationally and worldwide, with 95% resulting in hip fractures. Previous studies have found that the soft tissues (subcutaneous adipose and muscle) surrounding the proximal femur influence the magnitude and distribution of the impact force transmitted to the underlying bone during an impact, and thus hip fracture risk. However, there is a gap in the literature since studies have not explored the role of the soft tissues’ mechanical properties, particularly Young’s modulus, on the impact force magnitudes and distribution during both resting and muscle contracted states. This gap can be addressed using shear wave elastography (SWE), an ultrasound imaging technique that quantifies soft tissues' shear wave velocity (SWV). SWV can be used to compute the Young’s moduli of the tissues and gain a better understanding of the mechanical properties of the tissues. Investigating the SWV of the soft tissues would help improve the biofidelity of physical and computational hip models, which would allow us to better understand lateral fall impact dynamics and help to improve the design of hip fracture prevention technologies. Objectives and Hypotheses: There were two main objectives of this thesis. The first objective was to evaluate the intra-rater reliability of the SWE protocol used to characterize the SWV of the soft tissues (subcutaneous adipose and muscle) in the lateral-hip region, and the potential influence of muscle contraction on intra-rater reliability. The second objective was to assess the influence of muscle contraction on the soft tissues’ SWV. Based on the previous literature, it was hypothesized that: 1) the intra-rater reliability of the subcutaneous adipose and muscle SWV measurements taken with this protocol would range from good to excellent (ICC > 0.75), and would not be influenced by contraction state, and 2) there would be an interaction effect of muscle contraction on the SWV magnitudes of the soft tissues. It was expected that: a) the muscle SWV magnitude would be greater during the muscle contracted state compared to the resting state, while b) the subcutaneous adipose SWV magnitude would not change during the resting and muscle contracted states. Methods: Twenty healthy, young adults between the ages of 18-35 years with a BMI ≤ 24.9 kg/m2 were recruited. The elastography setting on the GE LOGIQ E10 commercial ultrasound machine and a linear probe were used to take 3 measurements of the muscle and subcutaneous adipose tissues from a marked location on the participants’ left lateral hip region. Three measurements from each tissue were taken during the muscle relaxed and contracted states, resulting in 12 measurements being collected from each participant. A two-way mixed effects absolute agreement intraclass correlation (ICC) model was used to assess the intra-rater reliability of the measurements and the influence that muscle contraction had on it. A two-way repeated measures analysis of variance (ANOVA) was used to assess the potential interaction effect of muscle contraction on the SWV magnitudes of the soft tissues. Results: As hypothesized the intra-rater reliability of the subcutaneous adipose and muscle tissues ranged from good to excellent (0.81 < ICC < 0.95) and was not influenced by contraction state. This aligned with previous literature and supported that the protocol was appropriate for examining the influence of muscle contraction on SWV (Objective 2). Two-way repeated measures ANOVA revealed a significant interaction effect of muscle contraction on the SWV magnitudes of the soft tissues (p < 0.05), which was particularly driven by the significant increase in the muscle’s SWV from resting to contracted state (p < 0.001). In contrast, the subcutaneous adipose’s SWV was not different during the two conditions (p = 0.825). These results aligned with the hypothesis and indicated that the moduli of the soft tissues in this region respond differently between relaxed and contracted states. Discussion and Conclusion: The protocol used in this thesis had good to excellent intra-rater reliability and can be used to characterize the moduli of the soft tissues in additional locations in the hip region. Additionally, the influence of BMI and aging on the stiffness of the soft tissues in this region can also be investigated. Muscle contraction also influenced the SWV of the muscle, while the SWV of the subcutaneous adipose did not change. This finding indicates that the soft tissues in the hip have unique properties and respond differently to muscle contraction. Accordingly, it is worth exploring whether they should be modelled separately in biomechanical models of the hip and pelvis. Implementing this finding in physical and computational models that currently bulk together the properties of the soft tissues in the hip, should improve their biofidelity. Additionally, the protocol used in this thesis, along with the differences observed in the soft tissues’ SWV, can potentially be used to assess muscle quality. Since alternative modes on the ultrasound, such as echo intensity, are currently used to assess changes in muscle quality, SWE may be an alternative technique that can be used.

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