Kinesiology and Health Sciences

Permanent URI for this collectionhttps://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).

Waterloo faculty, students, and staff can contact us or visit the UWSpace guide to learn more about depositing their research.

Browse

Now showing 1 - 20 of 506

Effects of Phospholipase A/Acyltransferase-1 (Plaat1) gene deletion on brain molecular and biochemical measures and memory
(University of Waterloo, 2025-10-30) Cocco, Alex
Phospholipase A1/2 and Acyltransferase-1 (PLAAT1) is a small lipid metabolizing enzyme that possesses transacylase activity and is expressed highly in the rodent heart and brain. Recently, our lab has found that in vitro, PLAAT1 is capable of acylating monolysocardiolipin with an acyl chain donated from phosphatidylcholine acyl donors to produce cardiolipin. Cardiolipin is a glycerophospholipid that is essentially exclusive to the mitochondria and is vital for trans-membrane protein stability, inner mitochondrial membrane structure, apoptosis, and more. The de novo synthesis and acyl chain alterations (‘remodeling’) of cardiolipin are important for the health and proper functioning of cells. Previous work in our lab has demonstrated that mice deficient in Plaat1 (Plaat1-/-) had significant deficiencies in cardiac cardiolipin content, suggesting an in vivo role of PLAAT1 in cardiolipin metabolism. However, Plaat1-/- mice are poorly characterized, especially with regards to the brain, and study of this tissue, and phenotypic changes related to brain function, could help to delineate the role that PLAAT1 may serve there. Thus, the purpose of this thesis project was to explore the effects of Plaat1-deficiency on mouse brain cardiolipin metabolism and related functions. Lipid analyses of cardiolipin, monolysocardiolipin and phosphatidylcholine revealed small, sex-specific alterations in composition but not content, while analyses of gene expression for relevant biosynthetic and remodeling enzymes exhibited significant transcriptional downregulation in female but not male Plaat1-/- brains. Immunoblotting for mitochondrial protein markers suggested changes to mitochondrial shape in female Plaat1-/- brains, while both male and female Plaat1-/- brains experienced perturbations in subunit content for complexes of the electron transport chain. Lastly, mouse anxiety and short-term memory behaviour was tested, revealing that female Plaat1-/- mice are relatively anxiolytic (relaxed), while neither male nor female Plaat1-/- mice had altered short-term memory. Taken altogether, the data collected in this project suggests that PLAAT1 acts in a tissue- and sex-specific manner for reasons that were unable to explored within the scope of this thesis project. The present thesis project demonstrates both a cellular and physiological role of PLAAT1 in the female brain, and provides a foundation from which further work on PLAAT1 can be explored. These results have implications for the interaction of sex and cardiolipin metabolism in the function of brain mitochondria and resultant behavioural outcomes.
Cybersickness: Linking Postural Control to User Discomfort in a Virtual Roller Coaster
(University of Waterloo, 2025-10-23) Gulifeire, Alimu
Cybersickness (CS) remains a major obstacle to the widespread use of Virtual Reality (VR), with leading explanations emphasizing sensory conflict, sensory reweighting, and postural instability. Prior research has shown that individuals who flexibly reweight visual, vestibular, and body cues report lower CS, particularly in interactive VR tasks where users can move freely. Whether this relationship generalizes to more passive, visually intense VR experiences is less clear. This thesis examined sensory cue reweighting and postural control as predictors of CS during an immersive roller coaster simulation. Nineteen younger adults completed the Oriented Character Recognition Task (OCHART) before and after VR exposure to estimate perceptual upright and quantify cue weightings. During VR exposure, postural movement was recorded using markerless motion capture, and participants reported symptoms using the Fast Motion Sickness (FMS) scale after each trial. Contrary to findings from interactive VR contexts, sensory reweighting was not significantly associated with CS in this passive roller coaster environment. In contrast, measures of postural control, particularly total path length, were robust predictors of sickness severity, with greater displacement linked to higher FMS scores. These findings suggest that in visually dominant VR tasks with limited bodily engagement, postural instability provides a more reliable marker of CS than sensory reweighting. This work clarifies that the predictive value of sensory reweighting is context dependent, emerging more clearly in interactive than passive VR tasks. It further points toward movement-based strategies for mitigating discomfort in VR experiences where movement is restricted but visual conflict is high.
The Role of Binocular Vision in Visuomotor Control during Discrete Pointing and Reciprocal Tapping
(University of Waterloo, 2025-09-22) Wang, Shirley
Visual information is integral for executing movements in most daily activities. The accuracy and precision of upper limb movements towards targets are highly dependent on movement planning and the online monitoring of visual feedback. Investigating the effects of amblyopia and strabismus could provide insight into the neuroplasticity of visuomotor control. This study had two objectives: (1) to assess the role of binocular vision in two types of tasks, and (2) to investigate the impact of amblyopia and strabismus on visuomotor control. Two groups of participants were recruited: visually normal adults (n = 40) and patients with amblyopia and strabismus (n = 8). Participants were asked to perform two visuomotor tasks: discrete pointing and reciprocal tapping. For the discrete pointing task, participants pointed to a visual target at either 5º or 10⁰ along the horizontal meridian. For the reciprocal tapping task, participants repeatedly tapped between two targets of various sizes as fast and accurately as possible. For visually normal adults, binocular viewing resulted in faster movements compared to viewing with one eye, demonstrating a binocular advantage for motor efficiency for both discrete and reciprocal tasks. Patients with amblyopia and strabismus executed slower, more cautious movements when viewing with their amblyopic (non-dominant) eye compared to binocular and fellow (dominant) eye viewing. The patients also had significantly better movement performance when using binocular viewing compared to fellow eye viewing for the discrete task, suggesting there was some binocular advantage. The patient group tended to execute their movements faster but was less precise than the control group, suggesting a speed–accuracy trade-off. It is important to acknowledge that the current patient cohort was small and the results should be considered with caution. Nonetheless, the findings demonstrate that binocular vision plays an important role in facilitating the accuracy and precision of upper limb goal-directed movements.
The Effects of Chronic Psilocybin Administration on Physiological, Metabolic and Behavioural Outcomes in Control and High-Fat Diet-Fed Male and Female C57BL/6J Mice
(University of Waterloo, 2025-09-22) Diaguarachchige De Silva, Kalsha
Psilocybin, the prodrug, and psilocin, the psychoactive compound and serotonin receptor agonist found in Psilocybe mushrooms has been used by Mesoamerican communities for thousands of years for spiritual and medicinal purposes. In Canada, psilocybin is designated as a Schedule III substance prohibiting its use recreationally and in research. However, in 2018, psilocybin received “Breakthrough Therapy” status from the United States Food and Drug Administration, due to its impressive safety profile, and clinical evidence in the treatment of several psychiatric disorders, including substance-related and addictive disorders, when used in conjunction with psychotherapy. While obesity, which affects 1 in 4 Canadians, can be associated with a number of contributing factors; for those affected by overeating, obesity shares neurobiological and environmental parallels with other addictive disorders. For this reason, psilocybin is of interest as a potential treatment for obesity. To date, only three pre-clinical studies have examined psilocybin in diet-induced obesity models, and none have studied its chronic effects in female animals or effects on metabolic parameters, glucose tolerance and insulin sensitivity. Therefore, this thesis investigated the expression of serotonin (5-HT) receptors in 3T3-L1 adipocyte differentiation, in addition to the physiological, metabolic and behavioural effects of chronic psilocybin administration in female and male mice fed control diet (CD) or high-fat diet (HFD). In doing so, the expression of 5-HT receptors involved in regulating feeding behaviour and satiety (i.e., 5-HTR1B, 5-HTR2A-C, 5-HTR3 and 5-HTR7) were examined in 3T3-L1 adipocytes over 16 days of differentiation. Interestingly, only the expression of 5Htr2a significantly changed during differentiation, further signifying its vital role in regulating lipogenesis. Other than 5-HTR1B, which was expressed but did not vary during differentiation, all other 5-HT receptors showed minimal or no expression in differentiating and mature adipocytes indicating their rather dispensable role in these cells. In subsequent studies, eight-week-old male and female C57BL/6J mice were randomized to receive a 45 kcal% HFD or 10 kcal% CD for 17-weeks to induce divergent body masses, then they were further randomized to also receive weekly i.p. injections of 1 mg/kg psilocybin or vehicle (isotonic saline) for an additional 19-weeks. Towards the end of the injection period, mice were subjected to a test battery consisting of behavioural and metabolic tests: open field testing and elevated plus maze to monitor the movement of mice and to assess for anxiolytic behaviour; the Oxymax Comprehensive Lab Animal Monitoring System by Columbus Instruments® to assess respiratory gas exchange and ambulatory, rearing and total locomotion over a 24-h period; the Low-Profile Wireless Running Wheels by Med Associates® to assess voluntary running; glucose tolerance and insulin sensitivity testing to evaluate glucose response; and food intakes and body weights were measured on a weekly basis for the duration of the study, while organ weights were collected at study termination. Collectively, all studies showed no differences in body weight, food intake, respiratory gas exchange, organ weight, glucoregulation, anxiolytic behaviour or spontaneous movement following chronic psilocybin treatment in HFD-fed male and female mice when compared to the CD-fed mice. Although there were no differences due to drug treatment, differences due to diet were present in nearly all the measures evaluated. Contrary to my hypotheses, psilocybin was unable to correct and restore the physiological, metabolic and behavioural alterations caused by HFD feeding to CD-fed levels. Nonetheless, CD-fed male mice treated with psilocybin had improved insulin sensitivity compared to all other groups. This novel finding leads us to speculate a role for psilocybin in glucose regulation, which may be elucidated in future studies. Therefore, this thesis, through its proposed studies, answered a vital question – chronic psilocybin treatment does not affect satiety or feeding behaviour in mice.
Understanding the relationship between gait and cognition in mild cognitive impairment subtypes and probable REM sleep behaviour disorder
(University of Waterloo, 2025-09-22) Elasfar, Salma
Introduction: Mild cognitive impairment (MCI) represents a transition state between normal cognition and dementia. Individuals with amnestic MCI (aMCI) are more likely to develop Alzheimer’s disease (AD), whereas individuals with non-amnestic MCI (naMCI) are more likely to progress to non-AD dementias. Individuals with multi-domain (MD-) MCI are more likely to develop dementia than individuals with single-domain (SD-) MCI. Previous research has demonstrated that individuals with MCI have slower gait compared to cognitively unimpaired (CU) older adults, but limited research has characterized gait differences across MCI subtypes over time in these groups. There is also growing evidence that specific gait characteristics are selectively associated with specific cognitive domains, but few studies have investigated these associations longitudinally in MCI. REM sleep behavior disorder (RBD) is a prodromal biomarker of α-synucleinopathies, particularly Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Individuals with RBD are more likely to develop MCI than healthy controls, and the presence of MCI in RBD is associated with greater risk for early phenoconversion. Recently, research has highlighted that individuals with isolated RBD exhibit subtle changes in gait. Despite this, no studies to date have explored how the presence of RBD influences gait characteristics in people with MCI. Therefore, this study aimed to a) characterize baseline and longitudinal gait characteristics across MCI subtypes, b) explore how the presence of RBD impacts gait characteristics in MCI, and c) assess whether baseline gait characteristics can predict future decline in specific cognitive domains in MCI. Methods: This study involved secondary data analysis of data from the Mayo Clinic Study of Aging. 382 individuals with MCI (180 SD-aMCI, 48 SD-naMCI, 134 MD-aMCI, 20 MD-naMCI), and 382 age-, sex- and education-matched CU individuals were included. Mean follow-up duration for the entire sample was 16.8 months. Participants completed gait assessment using an instrumented gait walkway. Informants completed the Mayo Sleep Questionnaire, which was used to determine probable RBD (pRBD) status. Cognition was measured using domain-specific z-scores for attention, memory, language, visuospatial function, as well as global cognition. Linear mixed effects models were used to compare gait outcomes over time between groups and by pRBD status. Principal component analysis and linear mixed effects models were used to derive gait components and assess if they predict change in cognitive domains from baseline to follow-up visits. Results: All individuals with MCI walked slower, with shorter steps, longer step time, and increased double support (%) compared to CU individuals. Variability of step length, stride velocity and swing time were increased in MD-aMCI compared to CU individuals. Over time, stride velocity and step length decreased, and step time increased in MD-aMCI. The presence of pRBD was associated with decreased stride velocity and step length, and increased stride width and double support (%), particularly in MD-naMCI. Swing time increased over time in people with MD-naMCI and pRBD. Principal component analysis identified three gait factors: pace and stability, timing and rhythm, and variability. The pace and stability factor was negatively associated with global cognition and attention. Surprisingly, the rhythm and timing factor was positively associated with memory. Variability was negatively associated with global cognition and visuospatial function, but this association weakened at follow-up. Conclusions: Gait analysis may be a helpful tool to distinguish MCI from normal aging. Gait variability and slowing of gait may be specific markers of multi-domain impairment. Gait is impacted by comorbid pRBD in MCI, particularly in MD-naMCI. These findings provide further support for the notion of selective associations between specific gait and cognitive domains in people with MCI. Importantly, further investigation with longer follow-up duration, larger sample sizes, and integration of neuroimaging and fluid biomarkers is needed to better understand the role of gait in predicting future progression to dementia in individuals at risk.
Accumulation and Recovery of Prolonged Low-Frequency Force Depression at Different Intensities of Repetitive Isometric Contractions
(University of Waterloo, 2025-09-19) Friedel, Jared
Prolonged Low Frequency Force Depression (PLFFD) may impact performance in the workplace by influencing musculoskeletal disorder (MSD) risk or reducing force stability. PLFFD is a reduction in low-frequency stimulated force with little change in high-frequency stimulated force for long period after contraction. The objective of this research was to measure changes in PLFFD over exposure and recovery from a half-shift of an isometric contraction task at two intensities on separate visits, and to determine whether there is a relationship between PLFFD and force stability. Participants repetitively supported a weight with their elbow flexors for 4 consecutive 1-hour work-segments. Participants performed a low-force high-duty cycle and a high-force low-duty cycle workload-matched protocol on two different days. PLFFD and force stability were measured in the biceps brachii muscle throughout task exposure and recovery. PLFFD was measured as the ratio of elbow flexion force produced at low (10 Hz) and high (100 Hz) frequency transcutaneous stimulations on both the left (non-intervention) and right (intervention) arms. A repeated measures ANOVA detected a progression of PLFFD in the intervention arm through intervention and recovery, but no protocol-effects were detected. Force stability metrics of variability (normalized standard deviation) and unsteadiness (average rate of change) of force during an isometric elbow flexion force matching task were poorly predicted by PLFFD and better predicted by changes in Maximum Voluntary Force (MVF). This research expanded on incidental findings of PLFFD from past research, and reinforced relationships between muscle fatigue and force stability. PLFFD did not recover at different rates depending on exertion intensity, nor impact force stability metrics, therefore likely not affecting worker performance. Muscle fatigue was shown to impact force unsteadiness to a greater extent than force variability, leading to the suggestion that force stability changes caused by muscle fatigue should be considered when designing a workplace.
The Effect of Jaw Clenching on Extracranial and Intracranial Blood Flow
(University of Waterloo, 2025-09-19) Zafiris, Eudoxia
The internal carotid artery (ICA) and external carotid artery (ECA) facilitate perfusion to the intracranial and extracranial regions, respectively. Under current dogma, the ICA is tightly regulated to ensure stable cerebral perfusion, while the ECA remains more pressure-passive, compensating for fluctuations in blood flow to the brain by redirecting blood flow to protect the cerebrovascular network during physiological stressors. While previous research has attempted to influence ECA flow through indirect stimuli such as facial cooling and exercise, direct experimental manipulation of ECA flow has rarely been tested. It remains unclear how ICA and ECA branches reallocate flow in response to changing demands in the facial vasculature. The purpose of this research is to determine whether the ECA can directly control carotid flow redistribution via jaw clenching by increased facial flow resistance and a post-exercise hyperemic response. 26 healthy adults (24±4 years; 15 female) performed isometric (25% maximum voluntary jaw clench (MVJC); 60 sec) and dynamic (50% duty cycle 3 seconds ON/OFF, for 60 sec at 75% MVJC) jaw clenching exercises. Additionally, a facial cooling mask was placed on each participants face to elicit a non-metabolic vasoconstrictor response. Blood velocity in the CCA, ECA and ICA was measured with conventional Doppler ultrasound before, during, and post clenching periods, and before and during facial cooling. Transcranial Doppler ultrasound continuously recorded middle cerebral artery velocity (MCAv), and vector flow imaging (VFI) was used to scan the carotid bifurcation before and post jaw clenching to determine changes in blood flow patterns. During both isometric and dynamic jaw clenching protocols, CCA and ECA blood flow increased from baseline, during, and post clenching, accompanied by a decrease in the pulsatility index (PI) (p < 0.05), indicating that jaw clenching actively increases extracranial blood flow via the ECA. In contrast, no changes were observed in ICA blood flow and PI throughout isometric jaw clenching, however, during dynamic jaw clenching, blood flow increased during the post clench phase compared to the ON phase (p < 0.05) and the PI decreased throughout (p < 0.05). MCAv increased during dynamic clenching (p < 0.05). The resistance index decreased during clenching and rebounded post clench for both jaw clenching conditions (p < 0.05), suggesting that intracranial responses depend on the clenching modality. VFI revealed that isometric jaw clenching increased flow and uniformity at the carotid bifurcation, reflecting laminar redistribution between the ECA and ICA. These findings provide novel evidence that jaw clenching can modulate carotid hemodynamics at both extracranial and intracranial levels and reshape local flow patterns at the carotid bifurcation. This has potential implications for understanding vascular contributions to temporomandibular disorders and the broader cerebrovascular impact of chronic jaw muscle activity.
The Association Between Physical Activity and Sleep Quality on Risk of Anxiety and Depression across Cognitive Statuses in Older Adults
(University of Waterloo, 2025-09-17) Ghodsi Boushehri, Maral
Introduction: Anxiety and depression are prevalent neuropsychiatric issues among older adults with cognitive impairment. They are associated with accelerated cognitive decline, increased caregiver burden, and reduced quality of life. Given the noticeable side effects of pharmacological treatments, there is growing interest in non-pharmacological approaches to tackle anxiety and depression. Physical activity and sleep quality have shown promise in reducing anxiety and depression in the general population, but their potential benefits remain largely underexplored in older adults with cognitive impairment. The objectives of this thesis were to: 1) examine the associations between physical activity and sleep quality with odds of having anxiety and depression among older adults with different cognitive statuses; 2) investigate whether physical activity moderates the association between sleep quality with anxiety and depression; and 3) explore whether the associations between sleep, physical activity, and anxiety and depression vary by dementia subtype. Methods: This was a secondary analysis of data from the Comprehensive Assessment of Neurodegeneration and Dementia study. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Anxiety and depression symptoms were assessed using the Generalized Anxiety Disorder 7–item (GAD-7) and the Geriatric Depression Scale (GDS). Cutoff scores of GAD-7 ≥ 5 and GDS ≥ 10 were used to identify participants who are likely to have at least mild anxiety or depression. Logistic regression models with a backward selection of covariates were used to evaluate associations. Results: The study sample included 956 older adults: 150 with no cognitive impairment, 116 with subjective cognitive impairment, 460 with mild cognitive impairment, and 230 with dementia. Poor sleep quality was strongly associated with increased odds of both anxiety (OR = 1.138, CI = 1.09–1.19, p < 0.001) and depression (OR = 1.355, CI = 1.137–1.646, p = 0.001). Increased physical activity was associated with lower odds of depression (OR = 0.996, CI = 0.994–0.999, p = 0.038), but higher odds of anxiety (OR = 1.003, CI = 1.000–1.006, p = 0.007). The relationship between physical activity and outcomes was consistent across cognitive groups, whereas the association between sleep quality and depression was weaker among people with dementia. Moreover, no significant interaction between sleep quality and physical activity was found, suggesting that there is no moderating effect in their relationship with anxiety and depression. Additionally, none of the associations varied by dementia type, indicating consistent relationships across different types of dementia. Conclusion: The consistent association between poor sleep quality and higher odds of anxiety and depression emphasizes the need to prioritize sleep interventions among older adults with various cognitive statuses. Physical activity may be beneficial in reducing depressive symptoms, but its unexpected positive association with anxiety highlights the need for further investigation.
Determining the maximum feasible box dimensions and box masses for one-handed box transfers from varying heights
(University of Waterloo, 2025-09-10) Li, Julia Xinyi
Background: To address continued prevalence of musculoskeletal disorders (MSD) related to manual materials handling (MMH) in logistics and warehousing industries, more effort is being devoted to proactive ergonomics when (re)designing the workspace through the use of digital human models (DHM). However, effectively using a DHM requires the user to estimate how a worker will interact with an object. One example includes guessing when a worker might use one hand versus two when lifting and transferring a box. To avoid guessing we need a better understanding of the determinants for performing one-handed lifts and transfers to inform DHM users on when human-object interactions should be modeled with one-hand verses two. Purpose: The aim of this work was to determine the maximum feasible box dimensions and masses that would permit a one-handed box lift and transfer from three shelf heights. Methods: Two sex-balanced samples of 20 participants completed a series of box transfer tasks from varying shelf heights (ankle, greater trochanter (GT), shoulder height) to a table with their dominant hand. For Study One, participants were instructed to grab a minimally weighed retractable box from either front or top and expand/collapse its dimension until they perceived that they could no longer transfer it with only one hand. For Study Two, participants were instructed to grab the box from either front or top (using the maximum acceptable dimensions from Study One) and to adjust the mass of the box until they perceived that they could no longer transfer it with only one hand. Within-subject repeated measure ANOVA with an alpha value of 0.05 were used for both studies to detect for shelf height or grip orientation differences. Results: The perceived maximum acceptable box width ranged from 70-73% of participant’s hand length. Perceived maximum width decreased with higher shelf height when grasping the box from the top, while staying consistent when grabbing the box from the front regardless of shelf height. Perceived maximum mass was lower when grasping the box from the top regardless of shelf height and was lower when grasping the box from shoulder height compared to ankle height regardless of grip orientation. Discussion: When the box width exceeded 124mm of the person’s hand length and required more than 36.7% wrist strength, people may be more likely to use two hands. The discrepancy in perceived maximum acceptable box width and box mass when grasping from the top at shoulder height was potentially due to awkward hand/wrists posture or line of sight issues. The effects between grip orientation and shelf height on the perceived maximum lifting capacity for one-handed transfers should be considered when proactively designing stock-picking tasks to optimize safety. Additionally, an understanding of the maximum determinants helped set manual material handling limits for one-handed box transfers. Findings from the current investigations provided psychophysical insights into the one-handed lifting capacity of standard cardboard boxes with no handles.
Exploring the use of the RCRA equation as an MSD risk assessment tool to evaluate electrical harness installation tasks.
(University of Waterloo, 2025-08-29) Nestor, Hailey Michelle
Intro: Electrical wire harnessing on an automotive line consists of routing a harness through a car’s engine, securing electrical connections, and successfully securing retention clips to keep the harness in place. The wire harnessing task is complex in nature and installation involves many hand forces and repetitive motions. Additionally, wire harnessing is highly repetitive, with workers having to install up to 500 engine harnesses per shift. Anecdotal evidence is emerging that some wiring harnessing work can lead to workplace musculoskeletal disorders of the hand and wrist. Due to the complex nature of the task, and difficultly in measuring internal exposures in-field by using tools such as electromyography, there is a lack of quantification and analysis of biomechanical demands of the task. The Recommended Cumulative Rest Allowance (RCRA) tool, developed by Potvin & Gibson (2016), aims to characterize exposures by assessing isolated subtasks in conjunction with other subtasks to assess the risk of a complete job. The RCRA is informed by percent efforts (%Efforts) that can vary and result in different outcomes based on inputs. Thus, there is a need to quantify and analyze biomechanical demands of wire harnessing using both high-fidelity in-laboratory equipment and potential lower-fidelity in- field equipment to compare and validate a cumulative tool to be used on the line. This study aimed to evaluate the usability of the RCRA tool for estimating required rest necessary to prevent undue fatigue during harness installation. Methods: Using a mock-engine setup in a controlled laboratory environment, 26 participants completed repeated installations of two harness types while surface electromyography (EMG) and force data were collected for wrist flexors, extensors, and applied hand force. RCRA ratios were calculated across subtasks and input types including muscle activity as a percent of maximum voluntary contraction of the wrist flexors and extensors and applied force as a percent maximum voluntary force to assess fatigue accumulation. Results: Findings revealed that input selection significantly influenced RCRA outputs, with applied force and wrist flexor EMG producing consistent and interpretable estimates of required rest allowances. In contrast, peak wrist extensor inputs often resulted in unrealistically high RCRA ratios due to the extensor muscle’s sustained activation patterns and the equation’s sensitivity to frequency and duration. No significant differences were found between the two harness types, likely due to their similar physical characteristics. Conclusion: Overall, this study supports that the RCRA tool yields similar outputs when driven with peak force or peak wrist flexor EMG, but not when driven with peak extensor EMG. It also underlines the need for careful input selection and complementary assessment strategies when evaluating different muscles. These insights provide a foundation for developing validated, in-field fatigue assessment protocols to help prevent overuse injuries in automotive manufacturing.
Investigating fiberglass casting materials and cross-system modality measurements in DXA and X-ray forearm imaging
(University of Waterloo, 2025-08-28) Ying, Tsz Yui
Falls on an outstretched hand (FOOSH) injuries often lead to distal radius fractures (DRFs). X-ray imaging is used to visualize fracture morphology and provide qualitative information; however, quantitative information is not readily available without more advanced imaging modalities. This study investigated the impact of fibreglass cast thickness on the accuracy of areal bone mineral density (aBMD) and bone mineral content (BMC) measurements obtained through Dual-Energy X-ray Absorptiometry (DXA). It evaluated the potential of a novel dual-energy spectral X-ray detector (Reveal 35C) as a point-of-care alternative. Eight cadaveric forearm specimens were scanned under baseline, two-roll, and four-roll cast conditions using both imaging modalities. Simulated DRFs were induced via quasi-static loading, followed by post-fracture imaging to assess structural integrity and imaging fidelity. Results showed that DXA-derived aBMD and BMC significantly decrease with increasing cast thickness. The mid-distal subregion of interest (MD-sROI) shows the most consistent attenuation trend. In contrast, the ultra distal (UD-sROI) and one-third distal (OTD-sROI) subregions of interest showed greater variability, particularly in specimens with lower density. The Reveal 35C detector showed a strong correlation with the DXA system under uncasted conditions (R2 = 0.82-0.89), but correlations are markedly lower in casted scans (R2 = 0.29-0.63). This discrepancy highlights cast-induced imaging distortions. Through fracture testing, it is shown that specimens with higher aBMD and BMC generally sustained greater loads prior to fracture. Findings from this study indicate that DXA-derived aBMD and BMC are susceptible to errors caused by fiberglass medical casts and variations in positioning during imaging. Meanwhile, the Reveal 35C system shows promise as a viable alternative for bedside fracture monitoring through calibration, but limited in enabling virtual cast removal and longitudinal assessment.
Validating Internal Density Calibration in The Proximal Humerus to Estimate Bone Stiffness Using Finite Element Analysis for Stemless Shoulder Arthroplasty
(University of Waterloo, 2025-08-26) Stiles, Chloë Karrie Anne
Stemless humeral head components are a popular choice for patients undergoing shoulder arthroplasty for end-stage osteoarthritis (OA). OA is known to alter bone density in the humeral head, which can compromise implant stability and increase the need for surgical revisions. Current pre-operative clinical assessments are limited in evaluating bone mineral density (BMD) and fail to consider the mechanical properties of bone in the region directly supporting the stemless component, leaving a critical gap in understanding the structural integrity of the bone supporting the stemless component. Traditionally, in-scan phantom calibration determines volumetric bone mineral density (vBMD) from greyscale intensity in computed tomography (CT) images, but this method is rarely used in clinical practice due to limited time and resources. As a result, alternative density measures for determining accurate vBMD from clinical CT images are needed. Internal density calibration using internal tissues as references has been validated in the spine and hip, however, it has yet to be validated in the proximal humerus. Additionally, vBMD derived from internal density calibrated images has yet to be linked to finite element model (FEM) apparent stiffness in the context of stemless shoulder arthroplasty. Establishing stiffness as a measure of bone mechanical properties is a first step in accurately predicting bone strength in clinical CT images. The purpose of this thesis was to 1) determine the correlation between phantom and internal density calibration in the proximal humerus using three different tissue combinations, 2) compare vBMD in an end-stage OA patient group to a non-pathologic group, and 3) determine the correlation between vBMD and apparent stiffness. Non-pathologic cadaveric single-energy CT images containing a dipotassium phosphate (K2HPO4) phantom were used to analyze a 10 mm thick volume of interest (VOI) directly below the anatomic neck. Phantom and internal density calibration was performed on each phantom-containing cadaveric specimen. vBMD was extracted and FEMs were generated from the VOI. The internal calibration with the lowest bias was used to calibrate images for all end-stage OA patient specimens. VOIs were created for cortical, trabecular, and combined (integral) bone compartments across specimens and vBMD was extracted for each compartment. FEMs were generated using the integral VOI to estimate apparent stiffness. Statistical analysis revealed a strong correlation between internal and phantom density calibration, establishing internal calibration as a valid metric for determining vBMD (AAdC R2 = 0.80; AAdCM R2 = 0.88; ACM R2 = 0.90). The ACM (Air, Cortical Bone, Skeletal Muscle) tissue combination had the lowest error (Mean: 13.08 mgK2HPO4/cm3). The end-stage OA patient group had significantly lower integral (Patient: 119 mg K₂HPO₄/cm³; Cadaver: 159 mg K₂HPO₄/cm³), cortical (Patient: 518 mg K₂HPO₄/cm³; Cadaver: 643 mg K₂HPO₄/cm³), and trabecular (Patient: 79.8 mg K₂HPO₄/cm³; Cadaver: 110 mg K₂HPO₄/cm³) vBMD than the non-pathologic cadaveric group (p<0.001), highlighting the biological relevance of vBMD. Mean apparent stiffness was found to be significantly lower in the end-stage OA group (672 MPa) relative to the non-pathologic cadaveric group (1261 MPa) (p < 0.001), however stiffness was not correlated with cortical vBMD in either group (Patient: R² = -0.018, p = 0.73; Cadaver: R² = -0.018, p = 0.71), suggesting the need for a multi-factorial approach when quantifying mechanical properties using FEMs.
Characterizing whole-body and regional adipose tissue distribution in older and younger adults
(University of Waterloo, 2025-08-25) Rosati, Katherine
Background: Aging is associated with a loss of skeletal muscle as well as a gain in whole body adipose tissue and increased fatty infiltration into muscle. Despite the known poor health outcomes associated with increased adiposity, there are sparce data regarding increased regional adipose tissue with age. Ultrasound has emerged as an accurate and precise body composition modality that can predict muscle and adipose tissue features, such as thickness and echointensity, and may circumvent many of the limitations associated with other body composition modalities. Thus, I sought to investigate adipose tissue characteristics across 8 anatomical landmarks characterized by weight-bearing and non-weight bearing regions of the body in a heterogenous population. Objectives: The primary objective of this thesis was to measure adipose tissue thickness at the anterior upper leg (AUL) and compare this site with 7 other anatomical landmarks in older adults using ultrasound: anterior upper arm (AUA), posterior upper arm (PUA), posterior upper thigh (PUL), anterior forearm (AF), abdomen (ABD), posterior lower leg (PLL), and anterior lower leg (ALL). The secondary objectives were to: 1) measure and compare adipose tissue echointensity at the AUL with the 7 other anatomical landmarks in older adults, 2) evaluate if sex and age are associated with adipose tissue thickness and 3) if sex, age and adipose tissue thickness are associated with adipose tissue echointensity. The tertiary objective was to evaluate the relationship between ultrasound-based adipose tissue thickness and echointensity when controlling for fat mass index (kg/m2). Methods: Healthy adults (>18 years old) were recruited for whole-body DXA scans and 8 regional landmark ultrasound scans. Anatomical landmarks were based on a 9-site protocol; from this iii protocol, 8 regional landmarks at the ABD, AUA, AF, PUA, PLL, ALL, AUL and PUL were used for the study. Whole-body DXA was used to determine physical characteristics including body fat percentage and fat mass index. Fat mass index (FMI) was calculated by adding all regional fat mass segments and dividing by height squared (kg/m2). Results: We performed a secondary analysis with 128 participants (42.9% females), including older adults (n=73, 74.1 +7.0 years of age) and younger adults (n=55, 27.1+6.9 years of age) . Adipose tissue thickness at the AUL was significantly lower compared to the ABD by 1.34 + 1.0cm, and was greater than the AF, AUA and ALL by 0.54 + 0.69cm, 0.39 + 0.59cm, 0.71+ 0.71cm respectively in older adults. Adipose tissue echointensity at the AUL was significantly greater compared to the ABD, AUA, PUA, PUL by 24.9+17.7a.u., 10.4+14.9a.u., 14.8+15.9a.u., 3.8+15.4a.u., respectively in older adults. Significant differences were observed across all nonweight bearing landmarks between older and younger adults. Regression analyses revealed sex and age non-uniformly influence adipose tissue thickness and echointensity across all 8 landmarks, even when controlling for FMI. Conclusions: This thesis demonstrated that older adults experience a non-uniform body composition distribution, specifically between weight bearing vs non-weight bearing regions. When compared to 7 regional landmarks, the AUL site had distinct adipose tissue thickness and adipose tissue echointensity in older adults, which may be attributed to age and sex, as shown by the independent and interaction effect of age and sex across all landmarks. Overall, this thesis determines the importance of investigating age-related adipose tissue distribution and applying non-invasive tools like ultrasound in the understanding of adipose tissue in diverse populations
Exploring the Exercise and Physical Activity Experiences of Adults with X-Linked Hypophosphatemia
(University of Waterloo, 2025-08-20) Morgante, Emmett
Background: X-linked hypophosphatemia (XLH) is a rare hereditary phosphate-wasting disorder, marked by mutations in the PHEX gene on the X chromosome. Mutations result in renal phosphate wasting and decreased 1,25-dihydroxyvitamin D, leading to rickets in children and osteomalacia in adults. XLH contributes to significant physical impairments including lower limb deformities, reduced height, bone pain, stiffness, early osteoarthritis, and fractures, which collectively hinder mobility, physical functioning, and quality of life. Despite pharmaceutical treatments, mobility and physical functioning deficits remain inadequately addressed. Currently, there is not a strong understanding of how physical activity and exercise can affect health outcomes for people with XLH. XLH brings unique challenges to mobility and physical functioning which could bring its own barriers to exercise making it an important topic to explore to create interventions for the XLH population. Objective: The objective of the study was to understand the experiences of people with XLH when participating in physical activity and exercise. I looked to identify how having XLH affects participation in physical activity and exercise, the barriers to and facilitators of exercise and physical activity, and the health outcomes that are most important for people with XLH when making treatment decisions with medications, and exercise. Methods: Using a phenomenological approach from a post-positivism point of view, semi-structured interviews were conducted with adults diagnosed with XLH. The interview guide was designed using the COM-B model of behavior to reveal how capability, motivation and opportunity affects people with XLH’s exercise and physical activity behaviors. Data was analyzed using reflexive thematic analysis to understand the experiences during exercise and physical activity, the barriers to and facilitators of exercise, and the outcomes prioritized by participants. A content analysis was done to understand the most frequent modes of exercise being completed, and the patient important outcomes most prioritized to participants. Results: Semi-structured qualitative interviews, and two content analyses with 17 adults who have XLH were conducted. Pain, stiffness, and fatigue were identified as major barriers to both a person with XLH’s capability and motivation to participate in exercise and physical activity. Pain and stiffness created mobility limitations challenging a person’s capability. Fatigue and overexertion led to increases in pain and stiffness. The exacerbation of pain and stiffness from fatigue led to a fear of worsening symptoms affecting people’s reflective motivation to exercise. While fatigue worsens symptoms and discourages activity, participants described that when they were able to find the right balance of physical activity and exercise with rest they found improvements in pain, stiffness, mobility and overall physical functioning. Walking, stretching, swimming/water aerobics and strength training were completed most frequently by participants. Key facilitators to exercising were strategizing movement to manage fatigue, and tailoring exercise for mobility impairments. The study also highlights the importance of identifying patient important outcomes. Similar outcomes were identified for treatment with medications and exercise (pain, fatigue, strength mobility and physical functioning). But physical functioning and its individual components, such as strength, were more highly prioritized for exercise, versus pain for treatment with medications. Regardless of the context, improving functional outcomes and progression of the disease in the long-term was of the highest priority. Conclusion: While pain, stiffness, and fatigue pose substantial barriers to motivation and capability to participation in physical activity and exercise, the findings reveal that appropriately tailored and balanced exercise can lead to improvements in physical functioning, mobility, and symptom management. Participants emphasized the need for tailored approaches that account for their unique physical limitations, and for the management of fatigue. Crucially, the study underscores the significance of centering interventions around patient-prioritized outcomes which are often underrepresented in current clinical approaches. The findings lay the foundation for developing informed, person-centered physical activity guidance and exercise interventions that address both the physical and psychological challenges of living with XLH, ultimately aiming to improve quality of life and long-term health outcomes.
Investigating and promoting lifestyle factors to improve sleep in people at risk for and with dementia
(University of Waterloo, 2025-08-20) Kuhn, Tara
Introduction: Sleep disturbance is not only associated with increased risk of dementia but is common after dementia onset and is a noted stressor for care partners. Physical activity may reduce dementia risk, as well as promote sleep for people with dementia. However, it is unclear whether physical activity and sleep interact to mitigate dementia risk or promote quality of life in people with dementia. This thesis aims to: 1A) understand the relationship between sleep, physical activity and cognitive function in people without dementia, and 1B) understand how sleep and physical activity relate to cognitive function and functional abilities among people with dementia, and 2) adapt a lifestyle-focused sleep intervention for Canadians with dementia. Aim 1: Data from the Rush Memory and Aging Project —which utilized accelerometers, a cognitive battery, and clinical expertise— was used to examine: how sleep and physical activity were associated with cognitive decline and dementia risk in people without cognitive impairment (Study 1); and how sleep and physical activity were associated with cognitive and physical function in people with dementia (Study 2). In Study 1, greater physical activity was associated with slower cognitive decline and reduced dementia risk. Additionally, more fragmented sleep was associated with worse baseline global cognition, but not cognitive trajectory or dementia incidence. In Study 2, physical activity was associated with better functional abilities, but not with cognitive trajectory or sleep fragmentation in people with dementia. Sleep fragmentation was not associated with global cognition or functional abilities among people with dementia. Aim 2: A lifestyle intervention for sleep (NITE-AD) that included sleep education, physical activity, and light therapy was adapted to be s appropriate for use in Canada (NITE-CAD). Based on the Knowledge to Action cycle, we approached this program adaptation in three steps. Step 1: identify the knowledge gap and determine availability of sleep programs for people with dementia in Canada. Step 2: assess the barriers and facilitators to knowledge use (Study 3) and determine which aspects of the program required requires modification. Using a qualitative descriptive design, semi-structured interviews were carried out with people with dementia and their care partners. Interviews were coded with a deductive content analysis, using the Behaviour Change Wheel as the guiding framework. Findings indicated winter conditions exacerbated previous challenging circumstances for people with dementia and winter physical activity participation was facilitated when people with dementia had appropriate equipment, access to facilities or cleared trails, and had their preferences met (e.g. indoor vs. outdoor activities, risk tolerance). Step 3 (Study 4) tailored the NITE-AD program with an advisory team using the results from Study 3 to create the NITE-CAD program. Changes included flexible physical activity options to support participation of people with dementia with diverse needs, contexts, and preferences, and minor wording and formatting changes. Conclusion: Sleep and physical activity were independently associated with cognitive functioning, with physical activity reducing cognitive decline and dementia risk in adults without dementia. However, the positive effect to cognitive function was not evident after dementia onset, although physical activity benefited functional abilities. Several barriers and facilitators for engaging in winter physical activity were identified for people with dementia, which should be kept in mind for future dementia interventions utilizing physical activity. Flexible options may be needed to accommodate the diverse preferences, abilities, and resources of people with dementia and care partners.
Investigating the contributions of the right temporoparietal junction in sensory reweighting and cybersickness
(University of Waterloo, 2025-08-18) Lynn, Alyssa
Accurate perception of body position relative to gravity relies on the integration of visual, vestibular, and proprioceptive inputs. In virtual reality (VR), conflict between these sensory inputs can cause cybersickness – a visually-induced form of motion sickness. Sensory reweighting – a neural mechanism which shifts perceptual reliance on specific sensory cues based on prior experience and cue availability – has been proposed as a mechanism to mitigate cybersickness. However, the higher-order neural mechanisms underlying sensory reweighting in VR remain unclear. This exploratory study examined the role of the right temporoparietal junction (rTPJ) — a region involved in sensory integration, salience, and conflict detection — in sensory reweighting and cybersickness mitigation. Before and after a high-intensity VR experience, participants completed the Oriented CHAracter Recognition Test (OCHART) to assess sensory cue weighting and ranked their cybersickness throughout the VR experience using the Fast Motion Sickness scale (FMS). During VR, transcranial direct current stimulation (tDCS) was applied to the rTPJ to modulate neural activity. We hypothesized that anodal stimulation would enhance rTPJ activity, promote more efficient sensory reweighting, and reduce cybersickness, whereas cathodal stimulation would have the opposite effects. Results showed no significant differences in sensory cue weighting or FMS scores across stimulation conditions. Additionally, there was no association observed between changes in sensory weights and cybersickness. These findings suggest that rTPJ stimulation before VR is insufficient to modulate sensory reweighting or alleviate cybersickness. Future research should investigate the effect of rTPJ tDCS before and after VR and consider vestibular-specific reweighting measures, such as the subjective visual vertical or postural measures, such as sway path length. More specific measures of sickness, such as the Simulator Sickness Questionnaire (SSQ) should also be considered to better quantify the changes in cybersickness subtypes.
The Effect of Acute Intermittent Hypercapnia and Exercise on Ventilatory Chemosensitivity and Cardiovascular Function
(University of Waterloo, 2025-05-27) Rynne, Paige
Ventilatory long-term facilitation (vLTF) is a form of respiratory plasticity triggered by intermittent hypoxia (IH) in the presence of CO2 (1,2,4,34). The manifestation of vLTF following intermittent hypercapnia (IHc) without concurrent hypoxia – particularly in combination with exercise- remains unclear. This study evaluated the physiological effects of IHc and moderate-intensity exercise on cardiovascular function and ventilatory control in the resting and exercising states. Twenty healthy participants (10F) completed a three-visit protocol, including two experimental exposures to either IHc (PETCO2 +5mmHg for 40s, intersped with 20s normocapnic normoxia) or continuous room air (control), each followed by an exercising and resting observational period (~45 minutes in total). At rest, the cardiovascular response to IHc was not found to be different from control. During exercise, heart rate (HR) increased following IHc and mean arterial pressure (MAP) significantly decreased (HR: +12bpm, p < 0.001; MAP: -8mmHg, p = 0.006), while both appeared stable in the time-matched control. Exercising peripheral hypercapnic chemosensitivity (PHC) appeared constant over time with IHc (+14 ± 25%), contradicting the significant decrease observed with control (-8 ± 20%, p = 0.017). While ventilation (V̇E) increased across both states following IHc relative to control, only resting V̇E was disproportionate to metabolic demand, as reflected by a lower %ΔV̇E/%ΔV̇CO2 ratio relative to control. These findings suggest the presence of exercise with IHc may have a modulatory role in the development or expression of cardiorespiratory plasticity, as well as implicating sensory long-term facilitation (LTF) as a contributor to vLTF. Finally, a progressive amplification in V̇E over the course of IHc, independent of CO2 stimulus intensity, is consistent with early-stage chemosensory gain. Collectively, these findings demonstrate that IHc without hypoxia can elicit key indicators of vLTF.
Knee Extensor Capacity Utilization and Stair-gait Biomechanics in Younger and Older Adults
(University of Waterloo, 2025-05-27) Rinaldi, Daniel
Stair-gait is a more challenging task than level-gait, particularly for older adults. Both ascending and descending stairs require greater lower extremity joint ranges of motion, vertical ground reaction forces, and external knee flexion moments than level-gait. Safe and efficient performance while negotiating stairs is largely dependent on adequate knee extensor muscle function. However, age-related declines to muscle quantity, quality, and function contribute to limitations in physical function and independence during activities of daily living, such as stair-gait. Consequently, compensatory movement strategies employed by the trunk may be a key mechanism by which those with reduced muscle function adapt to large knee joint demands encountered in daily activity. The large demands imposed by stairs paired with reduced muscle function among a growing ageing population poses a substantial threat to quality of life. A few studies have investigated knee extensor muscle utilization, a concept that describes the proportion of the maximal available capacity of the knee extensors that is used to complete a task. Knee extensor muscle utilization is greater in older adults compared to younger adults during walking and other tasks. A number of studies also demonstrate knee extensor muscle capacity utilization is larger during stair ascent and descent compared to level walking in both young and older adults. However, little data compare knee extensor muscle capacity utilization between young and older adults on stair negotiation; and no study has determined whether this is related to sagittal plane trunk kinematics. This study aimed to compare knee extensor capacity utilization during stair ascent and descent in older adults versus younger adults. A secondary aim was to determine if this knee extensor capacity utilization is related to sagittal plane trunk kinematics. Twenty-five healthy young adults (n = 16) aged 18-30 years and healthy older adults (n = 9) aged 45-70 years were recruited primarily from the University of Waterloo and surrounding communities. Three-dimensional kinematics and kinetics were captured while participants ascended and descended a custom-built 4-step staircase using a high-speed motion capture system as well as floor- and step-embedded force plates, respectively. Knee extensor capacity utilization was calculated from maximal voluntary isometric and isokinetic contractions via dynamometry and peak external knee flexion moments measured in the stance phase of stair-gait for both stair ascent and descent. A two-tailed Welch’s t-test was used to determine if there was any difference in knee extensor capacity utilization between the healthy young adults and healthy older adults. A Pearson-Product Moment Correlation test was used to determine the relationship between knee extensor capacity utilization and the peak trunk flexion angle during the stance phase of stair-gait. Healthy older adults exhibited significantly greater knee extensor capacity utilization compared to healthy younger adults (p = 0.02), but not while descending stairs (p = 0.62). Knee extensor capacity utilization was not associated with peak sagittal trunk flexion angles during the stance phase of stair ascent (r = -0.06; p = 0.77) or stair descent (r = -0.31; p = 0.14). Findings demonstrate that healthy older adults utilize a greater amount of their available knee extensor capacity than healthy younger adults during stair ascent but not during stair descent. KECU was not associated with peak trunk flexion while either ascending or descending the stairs. Overall, findings further support for stair ascent being more challenging for older adults than younger adults. This study provides insight into the impact of knee extensor weakness while negotiating stairs.
Investigation of the therapeutic potential of a new phytoceutical for lymphopenia in Barth Syndrome
(University of Waterloo, 2025-05-26) Chan, John
Background: Barth syndrome (BTHS) is a debilitating X-linked genetic disorder caused by mutations in the gene that encodes for Tafazzin, an enzyme important for cardiolipin (CL) remodeling. This disorder impairs the ability to modify fatty acyl chains on cardiolipin after de novo synthesis, resulting in decreased cardiolipin levels and alterations in cardiolipin fatty acyl composition. Given that CL is crucial for mitochondrial processes, TAFAZZIN mutations lead to abnormal mitochondrial ultrastructure, impaired dynamics, and decreased electron transport chain capacity. As a result, tissues with high energy demands, including the heart, skeletal muscle, and immune system, are most affected by BTHS. While BTHS research has traditionally focused on innate immune dysfunction, recent studies highlight potential adaptive immune impairments. Data from my MSc research demonstrated that transformed B-lymphoblasts derived from individuals with BTHS exhibit significantly reduced growth compared to sex- and age-matched healthy controls. This deficit was partially restored with the endocannabinoid N-oleoylethanolamide (OEA). However, while OEA showed initial promise, it only partially rescued the impaired clonal expansion of these cell lines. In the pursuit of compounds with potentially better efficacy and safety profiles, further investigations turned to a natural phytochemical known for its antioxidant and mitochondrial-modulating properties, which we refer to as Compound X. Aims and Approach: This thesis aimed to evaluate the therapeutic potential of Compound X in treating BTHS-associated lymphopenia. To achieve this, several objectives were examined by comparing responses in both BTHS and healthy B-lymphoblasts. Specifically, we: (1) assessed the effects of Compound X on cell growth using manual cell counting with a hemocytometer; (2) analyzed changes in CL content and composition following Compound X treatment via thin-layer chromatography and gas chromatography (TLC-GC); (3) evaluated the expression of genes involved in CL biosynthesis using RT-qPCR; (4) examined the impact of Compound X on ETC protein subunit levels using immunoblotting; and (5) investigated alterations in mitochondrial ultrastructure and morphology in response to Compound X treatment through transmission electron microscopy (TEM) and immunoblotting of fission and fusion mediators. Results: In the first study, Compound X treatment fully restored the impaired cell expansion of B-lymphoblasts derived from five distinct BTHS donors, bringing the cell number to near levels of healthy controls. This growth improvement was accompanied with significant increases in the maximal coupled state III respiration in BTHS B-lymphoblasts, in which all five tested BTHS donors had increased mitochondrial membrane potential following Compound X treatment. Further analysis revealed that Compound X treatment restored total CL content of BTHS B-lymphoblasts to healthy levels, but did not significantly alter the relative proportions of the major CL fatty acyl species. At the protein level, Compound X treatment reversed the decreased expression of major ETC subunits, including succinate dehydrogenase subunit A (SDHA), cytochrome c oxidase subunit 1 (COX1), and cytochrome c oxidase subunit IV (COXIV). TEM analysis of three distinct BTHS donor cell lines showed that BTHS lymphoblasts had abnormal cristae patterns with smaller total cristae lengths and enlarged mitochondria compared to healthy controls. While Compound X treatment did not significantly increase the length of cristae, it significantly reduced the mitochondrial enlargement in BTHS B-lymphoblasts. Lastly, immunoblotting of fusion mediators revealed elevated OPA1 levels in BTHS lymphoblasts, while analysis of the fission mediator DRP1 revealed elevated phosphorylation of its inhibitory site at Serine 637, both of which were significantly attenuated by Compound X treatment, suggesting a potential role for this compound in restoring mitochondrial dynamics in BTHS B-lymphoblasts. Conclusion: These findings demonstrate for the first time that Compound X effectively rescued the observed impairments in B-lymphoblast cell expansion in BTHS and partially restored BTHS B-lymphoblast mitochondrial function and morphology. However, additional experimentation in both animal models and humans are needed to further validate the therapeutic efficacy of Compound X in BTHS lymphopenia.
Dual energy CT for more accurate diagnosis and monitoring of early osteoarthritis-related shoulder injuries
(University of Waterloo, 2025-05-08) Quayyum, Sarah
The rapid acceleration of population aging has led to a growing prevalence of age-related musculoskeletal (MSK) conditions, such as osteoarthritis (OA). Dual-energy computed tomography (DECT) is an advanced imaging modality that shows promise in enhancing the diagnosis and characterization of MSK disorders by providing improved visualization of joint and tissue changes after injury. These advancements may support more effective treatment planning and better patient outcomes. The primary aim of this study was to refine input parameters used in DECT imaging and apply them to better understand the relationship between shoulder injury and early osteoarthritic changes over a six month period. This knowledge is expected to improve therapeutic outcomes and support early screening for individuals at high risk of developing OA. DECT was employed to quantify volumetric bone mineral density (vBMD) and to model bone stiffness and loading using finite element modeling (FEM) in both cadaveric specimens and participants. Three anatomical regions of the proximal humerus were assessed: the humeral shaft diaphysis, the articular surface of the humerus (humeral head), and the anatomical neck. Cadaveric scans were performed using both dipotassium phosphate (K2HPO4) and hydroxyapatite (HA) calibration phantoms while participants were scanned using only the HA phantom. Imaging was conducted using both BONE and Standard (STD) reconstruction kernels at three energy pair combinations: 40/90, 90/140, and 40/140 keV. These combinations were chosen to evaluate whether higher energy pairs could help mitigate attenuation issues commonly encountered at lower energy pair combinations. The BONE kernel was selected for its superior bone edge sharpening and contrast, whereas the STD kernel was used to enhance visualization of surrounding soft tissues. Participant imaging occurred at baseline (within six weeks of injury) and again at six-month follow-up. Results of this study demonstrated that both vBMD and FEM-derived stiffness values were significantly higher in the diaphysis when scanned using the BONE kernel at the highest energy pair combination (90/140 keV). In contrast, the anatomical neck consistently showed the lowest vBMD and stiffness values, with no significant differences in vBMD or FEM-derived stiffness values observed within the anatomical neck or humeral head regions under the same parameters. By developing patient-specific, image-based computational models, this study contributes to a deeper understanding of both biomechanical and imaging characteristics of early shoulder OA, potentially informing future diagnostic and therapeutic strategies.

Browse

Recent Submissions