Thesis (Ph.D.) - University of Queensland, 2003. / Includes bibliography.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Back pain is a very common musculoskeletal impairment in most Americans. Average annual occurrence of back pain is reported around 30% of the population and is the most common cause of activity limitation in people younger than 45 years old. Eighty percent of the back pain presents in the lumbar spine. Although this ailment is very prevalent in the American population, there is a lack of empirical evidence supporting the common clinical diagnosis and intervention back pain strategies. The frequency of back pain and the lack of treatment methods were the motivation for this investigation. It is important to better understand spine dynamics during ambulatory tasks of daily activities to identify possible biomechanical mechanisms underlying back pain. Current biomechanical quantification methods for spine dynamics are either too invasive or not detailed enough to fully comprehend detailed spinal movement. Therefore, a non-invasive but detailed procedure to calculate spine dynamics was developed and tested. In this study, multi-segmented spine dynamics (kinematics and kinetics) were calculated during four activities of daily living (level walking (W), obstacle crossing (OC), stair ascent (SA) and stair descent (SD)). Our findings suggested an in-vivo multi-segmented spine surface marker set is able to detect different and repeatable motion patterns during walking among various spinal segments. The sacrum to lower lumbar (SLL) joint had the largest range of motion (ROM) when compared to the other more superior joints (lower lumbar to upper lumbar and upper lumbar to lower thoracic). Furthermore, SA task demonstrated more flexion ROM than both W and SD tasks. In addition to task influence, joints at different spine levels also demonstrated different ROMs, where SLL had a greater ROM than upper lumbar to lower thoracic (ULLT) in the transverse plane. Age was found to not significantly affect the segmental spinal ROM or peak angles. The vertical segmental joint reaction forces were different between tasks, where SD yielded larger vertical reaction forces than W. Overall, findings from this dissertation work were able to show that a multi-segment spine marker system could be an effective tool in determining different spinal dynamics during various activities of daily living. This dissertation includes unpublished co-authored material.

Low back pain (LBP) affects many individuals worldwide. The established association between LBP and spine motor control has led to the development of many control assessment techniques. To understand the association between motor control and LBP, it is essential to understand the relationship between separate assessment techniques. Systems identification (SI) and local dynamic stability (LDS) are two methods commonly used to quantify spine control. SI provides a detailed description of control but uses linear assumptions, whereas LDS provides a “black box” non-linear assessment and can be quantified during dynamic movements. Although both SI and LDS techniques aim to measure the control of the spine, each employs different experimental setups and data processing strategies. Therefore, the purpose of this thesis was to compare the motor behaviour outcomes of SI and LDS quantification techniques. To do this, 15 participants completed two tasks (SI and LDS) in a random order. For the SI task, participants were seated and ventrally perturbed at the level of the 10th thoracic vertebrae (T10). They completed this task under instructions to resist the perturbations (resist condition) or relax and remain upright (relax condition). Admittance was represented using frequency response functions, and a validated neuromuscular control model quantified lumbar stiffness, damping and muscle spindle feedback gains. The LDS task involved participants completing three repetitive movement blocks consisting of flexion/extension, axial rotation, and complex movements. In each block, the maximum finite-time Lyapunov exponent (λmax) was estimated. A stepwise linear regression determined that λmax during the rotation task was best predicted by SI outcomes in the relax condition (adjusted R square = 0.65). Many conditions demonstrated no significant relationship between λmax and SI outcomes. These findings outline the importance of a consistent framework for the assessment of spine control. This could improve clinical assessment efficiency as well as the understanding of the association between LBP and motor control.

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M.Tech. (Chiropractic) / Please refer to full text to view abstract

Despite the importance of proper synaptogenesis in the CNS, the molecular mechanisms that regulate the formation and development of synapses remain poorly understood. Indeed, the mechanisms through which initial synaptic contacts are established and modified during synaptogenesis have not been fully determined and a precise understanding of these mechanisms may shed light on synaptic development, plasticity and many CNS developmental diseases. The development and formation of spiny synapses has been thought to occur via filopodia shortening followed by the recruitment of proper postsynaptic proteins, however the precise function of filopodia remains controversial. Thus the goal of this study was to investigate the dynamics of dendritic filopodia and determine their role in the development of synaptic contacts. We initially define and characterize short lipidated motifs that are sufficient to induce process outgrowth. Indeed, the palmitoylated protein motifs of GAP-43 and paralemmin are sufficient to induce filopodial extensions in heterologous cells and to increase the number of filopodia and dendritic branches in neurons. We showed that the morphological changes induced by these FIMs (filopodia inducing motifs) require on-going protein palmitoylation and are modulated by a specific GTPase, Cdc42, that regulates actin dynamics. We also show that their function is palmitoylation dependent and is dynamically regulated by reversible protein palmitoylation. Significantly, our work suggests a general role for those palmitoylated motifs in the development of structures important for synapse formation and maturation. We combined several approaches to monitor the formation and development of filopodia. We show that filopodia continuously explore the environment and probe for appropriate contacts with presynaptic partners. We find that shortly after establishing a contact with axons, filopodia induce the recruitment of presynaptic elements. Remarkably, we find that expression of acylated motifs or the constitutively active form of cdc-42 enhances filopodia number and motility, but reduces the recruitment of synaptophysin positive presynaptic elements and the probability of forming stable axo-dendritic contacts. We provide evidence for the rapid transformation of filopodia to spines within hours of imaging live neurons and reveal potential molecules that accelerate this process. / Medicine, Faculty of / Graduate

Multi-echo T2 relaxation measurements of the human spinal cord (SC) reveal a short T2 pool of water believed to arise from water trapped between myelin bilayers, where the proportion of this water to the total water signal is called the myelin water fraction (MWF). In the present study, MWF were measured in the healthy human cervical spine at the C4-C6 vertebral levels in vivo using a 3D modified 32 echo CPMG sequence to acquire axial slices perpendicular to the cord. Volunteers were recruited in two age ranges, under 30 years old and over 50 years old, and a subset of both groups were scanned twice to test reproducibility. Mean MWF in the dorsal and lateral column WM of the group under 30 years of age was 0.29 (0.01) (mean(SE)), which agrees with previously reported MWF values in the cervical spine. The mean absolute difference between two scans was 0.06 or 26%. A negative correlation between WM MWF and age was hinted at in these findings, however more subjects are required to improve statistical power. This study paves the way for the use of 3D myelin water imaging in the cervical spine at 3.0T for the assessment of SC WM pathology. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

The shape of the lumbar and thoracic spinal curves in healthy subjects, when standing and when adopting a variety of working positions, was investigated using angular measures. The hypothesis that spinal and pelvic posture is determined by body position was supported. The mechanism by which body position influences spinal and pelvic posture was investigated using angular indices of the lengths of the hip flexors and extensors. The hypothesis that hamstring stretch determines postural adaptation to sitting positions was not supported. A multivariate analysis revealed that an index of iliopsoas length was the best predictor of posterior pelvic tilt in a variety of sitting positions. A supplementary investigation was carried out using data on the range of motion of the pelvis in the different body positions and its relationship to the muscle length indices. The role of the hamstring muscles in sitting posture was clarified. Some electromyographic data is presented to further illustrate the effect of body position on the role of the hip and trunk muscles in posture. A replication of the main findings and an investigation of some of the practical implications of the work were carried out drawing attention to some mechanisms of postural stress, potential problems of increased lumbar lordosis and their cost-effective alleviation through workspace design. The provision of a footrest, for example, was found to have significant effects on lumbar and pelvic angles in standing as well as in sitting. Further research into standing posture in the workplace is indicated by these findings. Some hypotheses for future investigation are presented.

Intervertebral disc (IVD) degeneration (DD) affects over 40% of adults, is a leading cause of disability and costs over $100 billion in economic burden annually. DD is a multifactorial process ultimately leading to tissue breakdown and loss of functionality. DD is associated with increased levels of pro-inflammatory cytokines within the disc and the catabolic effect of inflammatory stimulation on disc cell biology has been well studied. As part of its physiological functioning the disc experiences mechanical, hydrostatic, and osmotic stimuli. Cells within the disc are mechanosensitive to these signals, where hyper physiological and damaging physical signals can perpetuate degenerative effects in the disc. Despite the known contributions of inflammatory stimulation and biomechanics to DD individually, the interaction of inflammation and biomechanics in the IVD is still not well understood. The objective of this thesis is to examine the role of inflammatory stimulation on cellular biophysical properties in the disc, subsequent implications at the tissue level, and its contributions to DD. Here the cell cytoskeleton and actomyosin contractility are identified as key regulators of the response of cellular properties to inflammation. Actomyosin contractility is further identified as a regulator of well-known biological responses to inflammatory stimulation within the disc including ECM catabolism and altered disc tissue mechanics. Altered cellular biophysical properties observed in clinical human DD samples indicate the inflammatory milieu present in DD drive changes in cellular mechanics. Increasing actomyosin contractility is shown to be effective in mitigating the effects of inflammation on cellular biophysical properties and subsequent degenerative effects highlighting its potential as a therapeutic for the treatment of DD.