Human Physiology Theses and Dissertations

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Open Access
Examining Mechanisms of Altered Skeletal Muscle Cellular Passive Mechanics in the Context of Acute Fatigue and Age
(University of Oregon, 2024-12-19) Privett, Grace; Callahan, Damien
Skeletal muscle stiffness influences locomotor function and may predict soft-tissue injury risk. Recent literature suggests fatiguing exercise transiently reduces whole skeletal muscle stiffness, yet the underlying mechanisms remain unclear. Therefore, the purpose of this dissertation was to i) determine whether fatiguing exercise reduces cellular passive stress and Young’s Modulus in conjunction with altered phosphorylation of the sarcomere protein titin, ii) extend these measures to samples of composite tissue, and iii) assess whether aging mediates the effect of fatigue on skeletal muscle passive mechanics. Methods: 9 young and 8 older males and females completed unilateral fatiguing exercise followed by biopsy of the fatigued and non-fatigued Vastus Lateralis. In younger adults, passive stress and strain were compared in fatigued versus non-fatigued single fibers and titin phosphorylation was quantified via liquid chromatography mass spectrometry (LC-MS, Aim 1). Cellular measures were then translated to bundles of 12-14 fibers with intact extracellular matrix (ECM, Aim 2). Finally, cellular and tissue-level mechanical measures were compared in young versus older adults (Aim 3). Results: We observed that fatiguing exercise reduced passive stress and Young’s Modulus in myosin heavy chain (MHC) IIA and IIA/X fibers from young and older males, but not females. Titin phosphorylation was altered by fatiguing exercise, with no apparent sex-based differences. In-vitro treatments to phosphorylate or dephosphorylate titin did not support a direct link between titin phosphorylation and altered cellular passive mechanics. In bundles, fatiguing exercise only affected passive modulus in young females, and this fatigue-induced difference was at least partially due to titin. Aging did not affect cellular or bundle passive measures, nor did aging mediate the response to fatigue. Discussion: These data suggest that fatiguing exercise reduces cellular passive stress and modulus in muscle from older and younger males, in conjunction with altered titin phosphorylation. Furthermore, intracellular proteins appear to contribute to tissue mechanics, though their relative influence is unclear. Ultimately this study contributes to efforts aimed at understanding the chronic and acute mediators of skeletal muscle mechanics.
Open Access
Maternal Health & Diet Programs Offspring Metabolism
(University of Oregon, 2024-08-07) Greyslak, Keenan; McCurdy, Carrie
Although adult sedentary behavior and poor dietary patterns can impact metabolic health and disease outcomes, studies in animal models and human populations have generated a convincing body of evidence to suggest that nutritional and hormonal insults during critical windows of development in early life can redirect future metabolic health outcomes in offspring independent of future lifestyle choices. Specifically, maternal phenotypes derived from chronic consumption of high-fat, high-sugar, low fiber “Western-Style” diets (WD), the presence of obesity, and/or the presence of maternal hyperandrogenemia (HA) during pregnancy place them and their unborn child at higher risk for developing chronic metabolic diseases like Cardiovascular Disease, Type 2 Diabetes, and Nonalcoholic Fatty Liver Disease.To better understand the mechanisms that lay the groundwork for metabolic dysfunction in offspring tissues beginning in utero, this dissertation has utilized a nonhuman primate model of chronic maternal WD consumption with and without the development of obesity on the metabolic health outcomes in juvenile and adolescent offspring. The added contributions introduced by postweaning diet style was also examined in these offspring. Finally, this thesis builds upon previous work tracking the reproductive and metabolic profiles associated with WD-induced obesity with and without HA in young female primates beginning in prepubescent juveniles and extending into adulthood. Finally, the independent and combined influence of HA with/without obesity during pregnancy on key aspects of fetal metabolism was also assessed.
Open Access
Influence of a Patent Foramen Ovale and Biological Sex on Thermoregulatory and Cardiovascular Responses at Rest and during Exercise
(University of Oregon, 2024-08-07) Bradbury, Karleigh; Lovering, Andrew
In healthy humans, core temperature (Tc) is maintained within narrow limits around ~37 °C. There is interindividual variability in resting Tc with most individuals between 36 and 37°C. Many factors contribute to the variability in the resting Tc including but not limited to, differences in basal metabolic rate, circadian rhythm differences, levels of inflammatory markers or endogenous pyrogens (i.e. tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, interferons), and menstrual cycle phase. Previous findings have also suggested that the presence of a patent foramen ovale in young, healthy men may be associated with elevations in resting esophageal temperature (Tesoph) that exist during thermal stressors (exercise, hot water immersion, cold water immersion). However, whether this difference in temperature exists in women with a PFO or whether this elevation in temperature is caused by differences in metabolic heat production are unknown. Additionally, while the elevations in temperature have been seen in a lab setting, whether the elevation in temperature influences self-paced 5k performance of thermoregulation during SCUBA diving is unknown. In Chapter IV, we demonstrated that during 60 min of exercise at a controlled heat production (7 w/kg) that men without a PFO have higher Tc compared to men with a PFO. However, there was no difference in the change in Tc over the course of the hour, suggesting that although there may be variability in the baseline temperatures among individuals, the presence or absence or a PFO does not influence mechanisms of thermoregulation during exercise. Additionally, no difference in baseline or exercise Tc or Tesoph existed between women with and without a PFO. In addition to Tc & Tesoph, we measured skin temperature, mean body temperature, heart rate and respiratory heat loss. There were no differences in any of these variables between PFO- and PFO+ groups. In Chapter V, we showed that men with a PFO have a greater increase in Tc despite slower running times compared to men without a PFO. However, contrary to our hypothesis and unlike previous studies, men with a PFO did not have higher baseline Tc. The greater increase in Tc during the 5k may be due to differences in heat production, time for heat storage (longer running times), differences in body composition/body weight or variability in ambient conditions. There were no differences in Tc or 5k performance between PFO+ and PFO- women. Finally, in Chapter VI, we demonstrated that the presence of a PFO had no effect on baseline or post-SCUBA diving core temperatures. We demonstrated that the most impactful predictors of the change in core temperature during a SCUBA dive were related to anthropometric characteristics such as body mass, body mass index, body surface area/mass ratio and wetsuit thickness.This dissertation includes previously unpublished material.
Embargo
A Comparison of Exercise Training and Heat Therapy for Improving Blood Pressure in Adults with Untreated Hypertension
(University of Oregon, 2024-08-07) Kaiser, Brendan; Minson, Christopher
Hypertension, or high blood pressure, represents a primary yet preventable risk factor for cardiovascular disease, kidney dysfunction, and cognitive impairment that impacts nearly 50% of United States adults. Physical activity is the primary lifestyle recommendation to lower blood pressure, but many people are unwilling or unable to engage in exercise training. Heat therapy, in the form of hot water immersion, dry sauna, or far-infrared sauna, has gained attention in recent years as a potential therapeutic alternative to exercise for improving blood pressure and cardiovascular disease risk, with secondary benefits for multiple organ systems, including the renal and cerebral circulation. While both exercise and heat therapy have been demonstrated as effective in a variety of populations, there are no studies that have directly compared these interventions for lowering blood pressure in adults with untreated hypertension. Therefore, the purpose of this study was to compare the efficacy of heat therapy and exercise training for improving blood pressure, renal function, and biomarkers of Alzheimer’s disease among adults with untreated hypertension. 41 adults were randomized to complete either 30 sessions of aerobic exercise training (n=20) or hot water immersion (n=21) over 8-10 weeks, with a battery of in-clinic and ambulatory assessments at baseline (PRE), after 15 sessions (MID), and after 30 sessions (POST). The impact of both interventions in this population was equivocal among outcome variables of interest, including both ambulatory and in-clinic blood pressure, pulse wave velocity, as well as biomarkers of renal function, cognitive function, and Alzheimer’s Disease. These findings help to inform future lifestyle interventions aimed at improving blood pressure and cardiovascular disease risk among adults with untreated hypertension.
Embargo
Systemic Cardiovascular and Carotid Baroreflex Support of Blood Pressure during Recovery from Passive Heat Stress in Young and Older Adults
(University of Oregon, 2024-03-25) Larson, Emily; Halliwill, John
Much like exercise, heat stress is a profound thermoregulatory, cardiovascular, and autonomic stressor which may promote a distinct post-stress recovery period marked by altered cardiovascular support of blood pressure. For example, several studies have noted a sustained reduction in blood pressure following a single session of heat exposure or “post-heating hypotension,” which is comparable to the sustained hypotension which follows a single session of exercise. While post-heating hypotension, like post-exercise hypotension, may act as a valuable “window of opportunity” in promoting blood pressure management, very little is known about the mechanisms supporting blood pressure regulation during recovery from passive heat stress. Furthermore, as advancing age increases the prevalence of hypertension and alters the thermoregulatory and cardiovascular responses to acute heat stress, it is clinically and scientifically important that investigations into the post-heating recovery period are conducted in both young and older individuals. This dissertation aimed to characterize and compare the systemic cardiovascular and carotid baroreflex support of blood pressure during recovery from whole-body, passive heating in young and older individuals. Temperature, central, and peripheral hemodynamics were evaluated in sixteen young and nine older individuals at normothermic baseline and during 60 min of passive heating (water perfused suit) and 2 h of normothermic recovery. The neck pressure technique was additionally used to assess carotid baroreflex control of heart rate, the peripheral vasculature, and blood pressure across these time points. Contrary to our hypothesis, a single session of passive heat stress did not promote a sustained reduction in blood pressure in young or older individuals. Furthermore, the systemic cardiovascular and baroreflex responses which accompanied acute heat stress were transient and did not persist beyond 1 h of post-heating recovery in young or older individuals despite continued elevations in core temperature. While these findings do not support the notion that the post-heating recovery period promotes robust and sustained alterations in the cardiovascular support of blood pressure, our novel characterization of the time course of thermal, systemic cardiovascular, and neurovascular recovery from whole-body, passive heat stress in young and older individuals fills important gaps in knowledge as we begin to understand the post-heating recovery profile.
Open Access
Heart Holes and Breath Holds: Influence of Sex and Intracardiac Shunt on Pulmonary Gas Exchange Efficiency and Association of Vascular Mediators on Blunted Hypoxic Pulmonary Vasoconstriction in Apnea Divers
(University of Oregon, 2024-03-25) Kelly, Tyler; Lovering, Andrew
Patent foramen ovale (PFO) has been documented in humans since Galen reported their existence approximately 2000 years ago. PFO has been associated with a variety of negative outcomes such as impaired ventilatory acclimatization to altitude and increased risk for high altitude pulmonary edema. However, the degree to which PFO impacts pulmonary gas exchange efficiency has remained under debate.Apnea diving presents unique challenges to the cardiopulmonary system. These challenges arise from the combination of physiological stressors created by diving, ranging from increased central venous pressure to severe hypoxia during the final ascent phase a dive. These unique stressors have created unique physiological adaptations in apnea divers. In Chapter IV the interaction of sex and PFO size, as determined by saline contrast echocardiography, is explored in participants at rest and while participating in moderate to strenuous exercise. The data in this chapter show that in females, but not males, with large PFO there is a significant impairment in pulmonary gas exchange efficiency. Additional work in Chapter V shows that percutaneous closure of PFO improves pulmonary gas exchange efficiency in women. Chapter VI examined the prevalence of PFO in apnea divers to non-diving controls, finding that divers are significantly more likely to have a PFO. Chapter VII utilized a 20- to 30-minute hypoxic challenge to investigate changes in pulmonary resistance in divers vs non diving controls. This chapter shows that apnea divers had a severely blunted increase in pulmonary resistance in response to hypoxia. Chapter VIII investigated potential mediators of pulmonary vascular tone in apnea divers and individuals breathing 11.5% oxygen for 7 to 10 hours, as well as whether there were differences in the circulating inflammatory milieu. The data presented in this chapter shows that apnea divers do not have greater bioavailability of nitric oxide nor greater endothelin-1 levels compared to non-diving controls. This dissertation includes previously published co-authored material as well previously unpublished co-authored material.
Open Access
Exploration of Corticospinal Excitability During Movement Preparation
(University of Oregon, 2024-03-25) Gomez, Isaac; Greenhouse, Ian
Action preparation is a vital component of healthy goal-directed movement. While several studies have found evidence of transient inhibition of the motor system prior to simple finger movements, the functional role and putative source of this inhibition is not well understood. We explored corticospinal activity during the preparatory state under a number of different manual task types and conditions to investigate the nature of movement preparation. We used single-pulse Transcranial Magnetic Stimulation (TMS) in combination with electromyography (EMG) to measure summary analogues of the motor output pathway during three different studies. The first was a delayed-response task involving button-presses with the index finger while the contralateral hand held a tonic contraction. Here we showed a release of inhibition in the non-responding hand, as evidenced in shorter cortical silent periods. Experiment two involved a two-dimensional reach across a tablet surface to acquire targets. Here, motor evoked potentials (MEPs) measured during reach preparation did not change from baseline. Experiment three was a delayed-response task involving a choice between an out-and-back reach across the tablet surface and a button press using the thumb and forefinger of the same hand. Here also MEPs during the preparatory period were unchanged from baseline. While these findings stand in contrast to previous findings, they may suggest that certain task-related parameters, such as feedback and task complexity may influence whether preparatory inhibition is observable. They also add to a small but growing body of work that challenges the proposed models of preparatory inhibition. This dissertation includes previously published co-authored material.
Open Access
The Examination of Inflammation, Iron Availability, and Patent Foramen Ovale as Factors that Influence Variability in Erythropoietin, Hemoglobin Mass, and Pulmonary Vascular
(University of Oregon, 2024-03-25) DiMarco, Kaitlyn; Lovering, Andrew
Individual variability in the cardiopulmonary system is often ignored in favor of focusing on group or treatment means. Erythropoietin (EPO) concentrations in response to renal hypoxemia, sea level hemoglobin (Hb) mass (Hb mass), and pulmonary vascular pressure changes in response to environmental stimuli are known to be markedly varied among individuals, yet very little research examines factors that may be responsible for that variability. Iron availability, immune system activity, and the presence or absence of a patent foramen ovale (PFO) are all factors that may play a modulatory role in EPO regulation, Hb mass, and pulmonary vascular tone regulation, yet our understanding of these factors in humans is largely unknown. In Chapter IV, we demonstrate that carbon monoxide (CO) inhalation (COi) and hot water immersion (HWI) independently and in combination (COi + HWI) increased EPO concentration to the same degree. Importantly, the increase in EPO was driven by females. Baseline iron availability and inflammatory cytokine concentrations did not predict EPO concentration in response to COi or HWI. This study emphasizes the need for future studies to examine mechanisms underlying sex differences in EPO concentrations in response to COi and HWI. In Chapter V, we show that some inflammatory cytokine concentrations and white blood cell counts moderately predicted Hb mass, but iron availability was the strongest predictor of Hb mass. The presence of a PFO did not alter Hb mass, although we do report lower ferritin in males with a PFO compared to males without a PFO. This study provides novel information that will provide direction to future research looking to utilize interventions aimed to alter Hb mass. Lastly, in Chapter VI, we demonstrated that SCUBA dives not requiring decompression on the ascent do not increase pulmonary pressure or resistance. However, some cytokine concentrations increased post SCUBA diving, so future research should examine the role of inflammatory cytokines in modulating pulmonary pressure during SCUBA dives requiring decompression that elicit increases in pulmonary pressure and resistance. This dissertation includes previously unpublished co-authored material.
Open Access
Exercise Interventions for Patients with Peripheral Arterial Disease
(University of Oregon, 2024-01-09) Harding, Aaron; Halliwill, John
Peripheral arterial disease (PAD) is atherosclerosis of the arteries outside of the heart and brain, particularly the lower extremities, and represents an advanced burden of cardiovascular disease. Patients with PAD have a high risk of morbidity and mortality. In addition, PAD leads to an accelerated decline in physical function and increased disability in both symptomatic and asymptomatic patients. Evidenced-based guidelines recommend walking in a supervised setting as the primary mode of exercise for patients with PAD. However, many patients are either unwilling or unable to tolerate the exercise due to the symptoms of claudication pain. The primary purpose of this dissertation was to expand on the standard practice and explore novel exercise and other training techniques that could improve the outcomes of patients with PAD.The study in chapter IV compared a novel combination treadmill and ambulation training protocol (COMBO) with a commonly used standard treadmill only training protocol (STAND) on patients with PAD. This was the first study to compare the difference between two training protocols on six-minute walk test (6MWT) performance in patients with PAD. The improvement in 6MWT total distance did not differ between the COMBO and STAND training protocols. However, both the 6MWT claudication onset distance and claudication onset time were greater in the COMBO group versus the STAND group. The results of this study suggest that ambulation training may improve 6MWT performance compared treadmill only training in patients with PAD. The study in chapter V investigated the effect of an active walking warm-up on the results of the 6MWT distance in patients with PAD. The study was the first to assess the effect of an active warm-up on the 6MWT in patients with PAD. The 6MWT total distance did not differ between the WARM-UP and NO WARM-UP conditions. Additionally, neither the 6MWT claudication onset distance nor claudication onset time differed between the WARM-UP and NO WARM-UP conditions. The results of this study suggest that an active warm-up of 10-12 minutes of walking on a treadmill at a workload between 1.4-2.1 METs may not be enough of a stimulus to increase 6MWT distance in patients with PAD. Chapter VI was a review article intended to explore novel exercise and other interventions that could challenge the current paradigm of exercise training for patients with PAD. This was accomplished by reviewing the literature showing improved outcomes, particularly 6MWT distance, with exercise in patients with PAD, discussing the current state of practice of PAD rehabilitation (SET for PAD), introducing overground ambulation in the supervised clinical setting, reviewing the literature on the effect of acute and chronic passive heating in patients with PAD, and discussing directions for future research with ambulation training and passive heating, two interventions that have shown improvement in 6MWT performance in patients with PAD.
Open Access
3D COACHING: SPORTS BIOMECHANICAL ANALYSIS OF COLLEGIATE ATHLETICS (TRACK & FIELD)
(University of Oregon, 2024-01-09) ADENIJI, OLA; Halliwill, John
Athletic (Track & Field) championships have showcased globally the great strength, power, and speed of athletes in a myriad of disciplines. Notably over the last 30 years, steady improvements in championship performances have intrigued the Athletics community—athletes, coaches, spectators—sparking interest to look further into how this caliber of athletes perform and what the training demands are to continue the pace of progress. Coaches, by nature, focus on what is familiar to them until the next ‘phenomenon’ in development and training becomes recognizable. In consequence, sports science research sources are perceived with complexity, and unused or misused by the Athletic community. Efforts led by leading sports scientists have been made in the live capture of world-class competitors during world championships to better understand, discuss, and use science within the current state of Athletics in published biomechanical reports. Although athletes have a critical role in whether achievements are met, coaching efforts are to serve the athlete's needs within the demands of each discipline. Balancing what an athlete can do biomechanically and the mechanism within a discipline is the challenge. Coaches often turn to the experiences that have built their coaching philosophy for guidance on the best approaches. With a focus on the NCAA collegiate championship, this project served as a biomechanical-driven evidence-based collection to better understand championship performance. The results justified achieving season-best sprint times and jump marks for higher seeding purposes. Furthermore, results underscored the high individuality in step characteristics during the development of acceleration and velocity of sprinters and jumpers. NCAA championships feature arguably the best collegiate and world-class competitors in Athletics. When the coaching and scientific views are taken into consideration at this level, an improved attempt at defining and appropriately applying mechanical principles to the technique and skills used can be established. Assessing kinematic parameters captured during these championships provides insight into biomechanical contributions in performances for coaches to evaluate and improve training design that will shape an athlete’s performance. An opportunity is available to add to the sports science narratives on the mechanics of Athletic disciplines using a biomechanics lens to magnify the coaches’ eye.
Open Access
UPPER LIMB MOVEMENT IN VIRTUAL AND REAL-WORLD ENVIRONMENTS
(University of Oregon, 2024-01-09) Spitzley, Katherine; Karduna, Andrew
In recent years, virtual reality (VR) systems have experienced significant technological advancements, resulting in increased accessibility and improved product quality. Early VR systems were limited by low visual quality, large size, and high cost, but advancements in technology have propelled VR into the mainstream. As VR becomes increasingly prevalent, it is vital to understand its effects on the human sensorimotor system, particularly with vulnerable populations. The upper limb is within the field of view of current VR headsets and is the main point of contact between the user and virtual environment. It is therefore an essential component of the relationship between user and system. This dissertation is organized into five sections, each contributing to the overarching objective of understanding upper limb movement in real and virtual environments. Chapter I serves as an introduction, providing essential background information and an overview of subsequent chapters. Chapters II and III are dedicated to validating the HTC VIVE tracker as a tool for collecting both static and dynamic data. This establishes the foundation for subsequent studies, which use the tracker to estimate body segment position and orientation. Chapter IV investigates the impact of visuoproprioceptive congruency on upper limb joint position matching within a VR environment, highlighting the pivotal role of vision in the planning and execution of movements. Continuing the exploration of upper limb movements, Chapter V identifies kinematic and kinetic disparities between visually guided reaching movements conducted in VR and the real world (RW). Building upon the findings from Chapter V, Chapter VI investigates the translation of these differences when individuals switch between VR and RW environments. Collectively, these studies contribute to the broader knowledge base of motor control, informing the design and implementation of effective protocols and applications in both real and virtual settings. This dissertation includes previously published and unpublished co-authored material.
Open Access
The Role of Maternal Obesity and Consumption of a Western-style Diet on Offspring Brain Development and Behavior via an Inflammatory Mechanism
(University of Oregon, 2023-07-06) Dunn, Geoffrey; Sullivan, Elinor
Currently almost 1 in every 3 women of childbearing age in the US are classified as obese. Consumption of a diet high in fats and sugars, such as the average American diet, is one of the largest predictors of increased levels of adiposity in an individual. Further, obesity is characterized in part by a low-grade chronic inflammatory state in peripheral circulation. Maternal obesity is a known risk factor for lasting impacts on neurobehavioral development in offspring. We therefore hypothesized that maternal consumption of a Western-Style diet and obesity-induced inflammation disrupts neurodevelopment of the serotonin system in the amygdala, increasing anxiety behaviors in non-human primate offspring. Indeed, our analyses suggest that maternal adiposity levels were associated with decreased offspring serotonin innervation in the amygdala which were associated with increased anxiety behaviors. Further, the number TPH2+ cells in the raphe nuclei, the site of serotonergic neuron cell bodies, were reduced in maternal WSD offspring. These finding suggested that maternal WSD and adiposity were associated with increased anxiety behavior in offspring through disrupting the development of the central serotonergic system during perinatal development.Further examinations of the mechanisms by which maternal WSD and obesity influence offspring neurobehavioral development suggest that obesity-induced inflammation is driving the observed perturbations in the serotonergic system. As the primary immune cell of the central nervous system, microglia play an integral role throughout perinatal neurodevelopment. Quantifying microglial number and morphology in the offspring amygdala suggested that maternal WSD and adiposity levels influenced microglia function throughout both pre and postnatal development. Specifically, maternal WSD appeared to elicit persistent effects on offspring microglia number while levels of adiposity appeared to have a more transient effect in prenatal development. These findings suggest that maternal WSD and obesity may elicit their effects on offspring neurobehavioral development through modulation of microglia during perinatal development. This dissertation includes previously published and co-authored material.
Open Access
Machine Learning and Wearable Sensors for the Estimation of Biomechanical Variables Outside the Laboratory
(University of Oregon, 2022-10-04) Donahue, Seth; Hahn, Michael
The miniaturization of sensors and their availability for biomechanical analysis outside of the laboratory has opened whole new areas of research. Wearable sensors have been developed to measure ground reaction forces, and inertial measurement units have been developed for the measurement of acceleration and angular velocity. The purpose of this dissertation was to develop methodologies for the measurement and estimation of biomechanical variables, outside of the laboratory. As these sensors can provide vast amounts of data, it is natural to leverage the strengths of machine learning models, which have been used to find patterns in large datasets to assist in the task of estimating biomechanical variables using wearable sensor data as input. This dissertation is divided into five distinct, but related projects all linked to the identification of gait events and machine learning applications for human locomotion data, both in and out of the laboratory. The first two projects were focused on identification of gait events and transitions between locomotion modes, while Projects 3 - 5 were focused on gait event detection and estimation of biomechanical parameters during running outside the laboratory. Project 1: Validation of a supervised machine learning algorithm for steady-state locomotion, and dynamic transitions between those locomotion modes. Project 2: Deployment of an unsupervised machine learning and heuristic gait event detection algorithms for the identification of gait events, across environmentally constrained and internally driven locomotion transitions Projects 3 - 5 resulted in the development of methodologies for biomechanical analysis. We utilized both heuristic and machine learning methodologies for the estimation of biomechanical variables in these scenarios. Project 3: Estimation of gait events and contact times from inertial measures on the foot and the sacrum in a semi-uncontrolled environment. Project 4: Implementation of a recurrent neural network for the estimation of whole ground reaction force waveforms and the calculation of discrete kinetic variables from these waveforms in a semi-uncontrolled environment. Project 5: Synthesis and application of the previous two chapters, gait event detection and estimation of ground reaction force waveforms on data collected in a real-world environment during a 5-mile free run.
Open Access
The Effects of Increasing Step Rate on Achilles Tendon Stress During Running
(University of Oregon, 2022-05-10) Farina, Kathryn; Hahn, Michael
Achilles tendon injuries are one of the most common running related injuries. Injuries to the Achilles tendon are painful, often involve long recovery and rehabilitation, and many patients are non-responsive to current treatments. One hypothesis for development of injury involves the combined action of frontal plane rearfoot motion and tibial rotation during the stance phase of running, leading to damage, and possible injury, within the tendon tissue if not given adequate time to recover. Targeting these actions of rearfoot motion may alter stress in the tendon, possibly decreasing injury risk, or providing alternate avenues of rehabilitation by addressing underlying movement patterns. The purpose of this dissertation was to evaluate how increasing step rate during running affects motion at the rearfoot and how changes in rearfoot motion affect stress in the Achilles tendon in healthy and injured runners. This dissertation was divided into three projects. Project 1 involved twenty healthy runners running with +5% and +10% increases in step rate on a force-instrumented treadmill, while motion capture data were collected. Results indicated increasing step rate significantly reduced peak rearfoot angles in the sagittal and frontal plane and reduced tibial internal rotation in the transverse plane. Project 2 used these previously collected data in a generic calcaneus and Achilles tendon finite element model to estimate changes in Achilles tendon stress as a result of increasing step rate. Conflicting results were observed, as the finite element model produced increased stress in the Achilles tendon with increased step rate but calculating stress with cross sectional area showed decreases in stress. Project 3 repeated procedures from Projects 1 and 2; however, runners with Achilles tendon injury were recruited for this final study, with magnetic resonance imaging scans of their injured leg used to create subject-specific finite element models. The results showed no significant differences in Achilles tendon stress with increased step rate, however results were variable between subjects. The results of this dissertation indicate increasing step rate significantly affects rearfoot motion; however, constraints in the finite element models and high subject variability led to inconclusive results concerning how increasing step rate affects Achilles tendon stress.
Open Access
Subacromial Shoulder Pain: A Look at Acute Muscle Pain, Acute Relief of Chronic Pain, and an Electromyography Normalization Technique
(University of Oregon, 2021-04-29) COOPER, JENNIFER; Karduna, Andrew
Shoulder pain is a common orthopedic concern. The pain has a wide range of possible causes and may progress in a number of different manners. One large gap in knowledge is the specific pathway of a chronic condition resulting from an acute injury. The purpose of this dissertation was to begin to close that gap from both ends, investigating muscular changes after acute pain is introduced and after chronic pain is acutely relieved. Additionally, an electromyography normalization technique was investigated as a means to facilitate research in a patient population. The results indicate decreases in rotator cuff muscle activity both with acute pain and the acute relief of chronic pain. This suggests acute reactions and chronic adaptations to pain differ and require further investigation.
Open Access
A Simulation-Based Framework for Informing Design of Prosthetic Feet
(University of Oregon, 2021-04-27) McGeehan, Michael; Hahn, Mike
Individuals with lower limb amputation face a variety of conditions associated with decreased quality of life, including elevated metabolic cost during ambulation, gait asymmetry, and a variety of psychological disorders. Sustained prosthesis use may also induce overloading of joints, leading to orthopedic injuries. These issues may be attenuated by improving user specificity in the design characteristics of foot prostheses. However, the effects of varied design parameters (e.g. stiffness) are not well characterized, and thus achieving meaningful improvements in gait mechanics has proven elusive. In order to achieve improvements, a robust understanding of the relationship between anthropometry, gait mechanics, and prosthesis design is necessary. Simulations based on computational gait models are powerful tools for evaluating potential biomechanical interventions, such as implementing a novel prosthesis. However, the utility of simulations to evaluate the effects of varied prosthesis design parameters on gait mechanics has not been fully realized due to lack of a readily-available limb loss-specific gait model and methods for efficiently simulating the mechanics of passive foot prostheses. The purpose of this dissertation was to develop computational models of a semi-active variable-stiffness foot prosthesis (VSF) and a limb loss-specific gait model to elucidate the relationships between anthropometry, gait mechanics, and variable prosthesis stiffness.This dissertation was divided into three distinct, yet related projects. Project 1 consisted of developing and validating a computational model of a VSF, a model of VSF-ground contact dynamics, and an optimization algorithm for programmatically deriving model parameters. In Project 2, a limb loss-specific gait model was developed and validated. Project 3 entailed developing a spatial contact model for the interface between the prosthetic socket and residual limb, and using that model for a simulation-based analysis of the effects of variable prosthesis stiffness on residual limb-socket dynamics. Projects 1 and 2 resulted in models and code for simulating gait with a VSF. Project 3 resulted in a reduced order spatial contact model of residual limb-socket interface dynamics. Simulated interfacial pressure and shear stress, as well as residual limb kinematics were similar to values previously reported in the literature. The effects of variable prosthesis stiffness on these outcomes were subject-dependent.
Open Access
Histamine and Cardiovascular Adaptation to Endurance Exercise
(University of Oregon, 2020-12-08) Sieck, Dylan; Hallwill, John
Adaptations associated with repeated aerobic exercise come in many forms and act synergistically to increase the amount of oxygen an individual can consume during exercise. Moderate intensity aerobic exercise causes increased histamine concentrations within the active skeletal muscle that is released from mast cell degranulation or de novo formation through the enzyme histidine decarboxylase (Steven A. Romero et al., 2016). Histamine activates H1 and H2 receptors on vascular endothelial cells and vascular smooth muscle cells of the working skeletal muscle to acutely cause vasodilation and promote increased blood flow. Exercise induced histamine release not only affects post-exercise hemodynamics, but also influences glucose delivery to skeletal muscle, mediates the normal inflammatory response to aerobic exercise, as well as mRNA expression following a single bout of exercise (S A Romero et al., 2016). Outside of the exercise-induced mRNA response, histamine release also mediates other signaling mechanisms that are indirectly involved with adaptation to exercise training such as angiogenesis and red blood cell maturation (Byron, 1877; Qin et al., 2013). Taken together, there is ample evidence that by repeatedly activating or antagonizing histamine receptors during exercise, physiological adaptations to repeated exercise stress could be modulated. The overall purpose of this dissertation was to determine the role of histamine receptor activation in adaptations to aerobic exercise training. We hypothesized histamine receptor antagonists would blunt positive physiologic adaptation, or gains in aerobic capacity, by effecting the ability to deliver and utilize oxygen during subsequent exercise. The results indicate that the ability to deliver oxygen through increased blood volume via hematopoiesis did not contribute to increased aerobic capacity and was not affected by histamine receptor blockade. However, the ability to deliver oxygen through increased angiogenesis (assessed via capillary density and corroborated by peak vasodilatory capacity) and utilize oxygen through increased SDH activity (corroborated by VO2peak) contribute to increased exercise capacity but that these adaptations occur either independent of the effects of histamine receptor activation or that adaptation is generated by redundant mechanisms in a highly resilient manner.
Open Access
Thermal Loading Modalities and Cutaneous Active Vasodilation
(University of Oregon, 2020-09-24) Francisco, Michael; Minson, Christopher
In humans, the primary response to increasing internal temperature is increased cutaneous blood flow along with sweating. These reflexes facilitate heat dissipation to the environment by expanding the thermal gradient between the core and the periphery of the body. The known mechanisms and transducers of cutaneous active vasodilation (CAVD) have been largely characterized by supine passive whole-body heating models and applied to our understanding of exercise heat loading. The goal of this dissertation was to assess the mechanisms of CAVD in response to varying thermal loading modalities and postures. First we sought to determine if posture could alter the nitric oxide component of CAVD. Second, we sought to confirm the cholinergic co-transmitter theory of active vasodilation during whole-body passive heating and expand these findings to exercise heat loading. Lastly, we sought to identify unknown vasoactive substances associated with cholinergic nerve co-transmission. Twenty four subjects were assigned to participated in one of two study protocols. Protocol 1 assessed neuronal and endothelial nitric oxide synthase (nNOS and eNOS) isozyme contributions to the nitric oxide component of CAVD during passive whole-body heat loading in the seated and supine positions. We found that eNOS is the primary mediator of NO during CAVD (Chapter IV). This finding conflicts with the findings of other studies, which have shown that the NO component of passive whole-body heat loading is mediated by nNOS. Protocol 2 assessed the cholinergic co-transmitter theory of CAVD during exercise and passive whole-body heat loading. As discussed in Chapter V, we found that both thermal loading modalities result in CAVD through cholinergic nerve transmission, and that vascular transduction of active vasodilator nerve activity was similar between the two modalities. The studies described herein provide evidence that CAVD is widely the same regardless of how thermal loading is accomplished. Despite exercise and passive whole-body heat loading having largely different hemodynamic and thermodynamic profiles, the afferent signals they share in common and those that delineate them do not appear to impact the mechanisms and transducers of CAVD as was originally thought. This dissertation includes published and unpublished co-authored material.
Open Access
Finding the Signal Within the Noise: Investigating the Interaction Between Histamine, Exercise, and Inflammation
(University of Oregon, 2020-09-24) Mangum, Joshua; Halliwill, John
Histamine is commonly associated with immune responses, typically involved in allergic reactions. It can be released in multiple tissues, including skeletal muscle during exercise; however, it is unknown what it is specifically about exercise that causes the release of histamine. In addition, the role of histamine in inflammatory responses implies that it may be involved in the acute post-exercise inflammatory response. Histamine’s role and context outside of exercise, such as its role in mediating sustained post-exercise vasodilation, has guided the creation and interpretation of the studies within this dissertation. This dissertation has two major aims, with multiple experiments addressing the first aim and one larger study addressing the second aim. The first aim was to determine what is the exercise “trigger” that causes the release of histamine during exercise in skeletal muscle. The data gathered from the studies within this aim suggest that increased skeletal muscle temperature, which occurs during exercise, may be the exercise trigger that is resulting in the observed increase in skeletal muscle histamine during exercise. Furthermore, data from Chapter V demonstrates there is a local factor or factors released from skeletal muscle during exercise that causes mast cells to degranulate more so than in resting conditions. Finally, the second aim sought to determine the role of histaminergic signaling in the acute post-exercise inflammatory response to aerobic exercise in untrained individuals. Our data suggests that histamine H1/H2 receptor antagonism using over-the-counter medications does not augment the systemic inflammatory response, out to 48 hours, following a novel bout of exercise in untrained individuals. While there was no effect of histamine receptor antagonism on systemic circulating inflammatory factors, future work should investigate how histamine receptor antagonism may affect inflammatory responses in skeletal muscle where histamine is formed and released. The findings of the studies within this dissertation highlight the interaction between exercise and histamine release in skeletal muscle. Further research expanding upon these findings will help to elucidate all the factors of exercise that may influence the release of histamine in skeletal muscle and the role of histaminergic signaling in the inflammatory milieu of skeletal muscle following exercise.
Open Access
Effects of Fatigue on Balance Control During Dual-task Walking
(University of Oregon, 2020-02-27) Chen, Szu-Hua; Chou, Li-Shan
Fatigue is one of the most frequently mentioned symptoms among older adults. Although there were many studies examining effects of fatigue on walking and balance control, the findings were inconclusive due to methodology discrepancy. In addition, the cognitive component is often neglected. Therefore, four studies were conducted in this dissertation to investigate how fatigue affects balance control during dual-task locomotion in older adults using a laboratory fatiguing protocol, and further, how these findings could be applied in real-life settings. In the first study, we demonstrated the use of a repetitive sit-to-stand protocol by examining changes in inter-joint coordination variability along the course of the protocol. The findings suggested that the knee-ankle coordination variability was higher towards the end of protocol. In the second and the third experiments, such fatiguing protocol was applied. Results from the second study suggested that participants regardless of age walked faster after fatigue when concurrently responding to a working memory test. Moreover, young adults showed a greater and faster mediolateral center of mass sway after fatigue; whereas older adults demonstrated a shorter reaction time from pre- to post-fatigue while maintaining a similar body sway during walking. The results from the third study followed the same trend, in which significantly deteriorated balance control during obstacle-crossing was only found in young adults but not in older adults. Taken together, healthy older adults might have a better adaptation to a fatigued status induced by a repetitive sit-to-stand protocol. In the last study, the connection between findings from laboratory experiments and real-life scenarios was explored through examining the effect of fatigue in three older workers following a day-long of occupational activities. Our results showed that some changes observed after work were in line with that observed in the laboratory, but some were opposite or demonstrated unique fatigue adaptations, such as increased body sway, which was not identified when the results were pooled together. Although conclusive interpretation could not be made given the descriptive nature of the study, it highlights the necessity of subgroup analysis and targets the future recruitment on fatigue-prone population. This dissertation includes unpublished co-authored material.