The neuromuscular response to prolonged lumbar flexion has recently been extensively studied in felines but has not been examined in humans. Animal studies suggest that prolonged lumbar flexion disturbs neuromuscular control of paraspinal muscles. This disturbance was linked to creep deformation of passive spinal tissues. Past research indicates that disturbance of paraspinal reflexes may limit spinal stability. The current study aimed to examine this behavior in humans. We hypothesized that prolonged lumbar flexion will disturb paraspinal reflex behavior in human subjects. Reflex behavior was quantified following a fifteen minute period of static flexion. There was a trend suggesting an increase in reflex magnitude after flexion (p = 0.055). This trend was only significant in female subjects (p < 0.003). Increased reflex following flexion was associated with a transient period of EMG hyperexcitability similar to felines. A second study was performed to quantify reflex behavior and creep deformation during flexion and recovery. Results indicated that creep occurred during prolonged flexion (p < 0.001). Reflexes were inhibited following flexion (p < 0.03). Both creep deformation and paraspinal reflex (p > 0.05) failed to exhibit significant recovery during the length of the test. Inhibited paraspinal reflexes may contribute to spinal instability and risk of low back pain for workers using flexed postures, due to the inability of the neuromuscular system to coordinate an appropriate muscle response following an unexpected loading event. Future studies must examine appropriate work/rest intervals for workers using flexed postures to limit reflex disturbance from prolonged ligament strain. / Master of Science

Falls from heights are the fourth leading cause of occupational injury and fatality in the United States. In particular, construction workers such as roofers are often exposed to high risk environments. Recent research has reported that a leading cause of falls among workers is a loss of balance. Therefore, in moving towards reducing the number of occupational falls, further investigation of balance and factors that influence postural control is necessary. The effect of neuromuscular fatigue has been addressed by many investigators; however, few studies have examined the effect of localized fatigue in muscles not located in the lower extremities. Because low back fatigue is so prevalent during manual labor, this investigation determined to study the effects of lumbar extensor fatigue on balance. Chapter 1 includes a complete review of current literature addressing the effects of muscular fatigue on measures of balance. Chapter 2 details an initial investigation of lumbar extensor fatigue on center of pressure (COP) based measures of postural sway and examines the effect of fatiguing rate. Chapter 3 examines the effects of different levels of lumbar extensor fatigue and expands on the previous investigation by examining center of mass (COM) movement and incorporating additional measures of postural control. The results of these investigations indicate that lumbar extensor fatigue affects both COP and COM measures of postural sway, and might also lead to an increased reliance on feedforward postural control mechanisms. These findings contribute to understanding of effects of fatigue on balance and may aid the future design of interventions aimed at fall prevention. / Master of Science

Astrocytes are the most abundant glial cell type in the central nervous system (CNS). Most astrocytes are born during the early postnatal period in the rodent brain and mature alongside neurons, demonstrating remarkable morphological structural complexity, and attaining maturity in the second postnatal month. We have shown that astrocyte morphogenesis is regulated in part by brain-derived neurotrophic factor (BDNF) via signaling through the truncated tropomyosin receptor kinase B (TrkB) receptor. TrkB is the primary receptor for BDNF which is broadly expressed and released by neurons in developing and mature brain. TrkB has two predominant isoforms expressed in central nervous system (CNS), the full length TrkB (TrkB.FL) receptor and truncated TrkB (TrkB.T1) receptor. We recently demonstrated in the adult rodent cortex that TrkB.T1 is largely specific to astrocytes and over 90% of all Ntrk2 expression in astrocytes attributed to TrkB.T1. In contrast TrkB.FL is the predominant isoform expressed by neurons. It is not known how astrocytes and neurons regulate their specific TrkB isoform expression, although previous studies in bulk frontal cortical tissue from human postmortem samples indicate that DNA methylation level in promoter region and 3' UTR region of NTRK2 is negatively correlated with TrkB.T1 expression levels, but not with TrkB.FL expression. The mechanism of TrkB.T1 isoform-specific expression and the role of TrkB.T1 in astrocyte developmental process are unknown. In this dissertation, we aimed to determine in the DNA methylation contributes to isoform specific expression of TrkB.T1. We thus profiled the 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in neurons, astrocytes and microglia utilizing nanopore sequencing. We identified robust differences in cell-type specific TrkB isoform expression is associated with significantly different 5mC and 5hmC patterns in neurons and astrocytes. Further, we investigated the role of TrkB.T1 in cortical astrocyte developmental processes and astrocyte function during early postnatal development (postnatal day (P) 8, P14, P28 and P60). RNA sequencing of TrkB.T1 deficient astrocytes isolated at these timepoints revealed aberrant gene expression in astrocyte maturation, while pathway analysis indicated disruptions in synapse organization, neurotransmitter transport and exocytotic processes. Subsequent functional secretory proteomics highlighted disruptions in metabolism and lipid regulation, particularly cholesterol transport, suggesting potential implications for synapse formation. We observed dysregulated spine density in the motor and somatosensory cortices from TrkB.T1-deficient astrocytes relative to control astrocytes. These findings suggest that TrkB.T1 deficiency adversely affects normal astrocyte development, which in turn affects neuronal synapse development. This study provides new insights into the role of BDNF/TrkB.T1 signaling in CNS development and lays the groundwork for evaluating astrocyte BDNF/TrkB.T1 signaling in neurological diseases. / Doctor of Philosophy / Astrocytes are an abundant brain cell type that play crucial roles in maintaining brain health and supporting neuron functions. Astrocytes develop right after birth and reach full maturity by the second month in rodents. Throughout life, astrocytes play crucial roles in stabilizing the brain's environment and supporting most brain functions. the formation of astrocyte complex morphology is regulated by brain-derived neurotrophic factor (BDNF), which interacts with a specific receptor called TrkB.T1 found mainly in astrocytes. Another form of this receptor, TrkB.FL, is primarily found in neurons. Despite the importance of TrkB.T1 in astrocyte development and function, the reason for high expression and its role in astrocytes were not well understood. Previous studies in human postmortem samples indicated that DNA methylation level of the gene NTRK2 is negatively linked to TrkB.T1 expression but not TrkB.FL expression. However, the mechanisms behind TrkB.T1 isoform-specific expression and its role in astrocyte development are unknown. In this study, we used advanced sequencing techniques to analyze DNA methylation patterns, a chemical modification that can control gene activity, in neurons, astrocytes, and microglia, which are three different cell types in the brain. Our study discovered distinct methylation patterns in all three cell types and supported previous research DNA methylation effect on gene regulation and alternative gene splicing. With the data obtain from this study, we also observed a significant difference in DNA methylation may cause that TrkB.T1 is mainly expressed in astrocytes and TrkB.FL is mainly expressed in neurons. The study further investigated TrkB.T1 deficient astrocytes at different developmental stages. By examining RNA from astrocytes, we found abnormal gene expression in astrocyte maturation. Further analysis showed changes in cholesterol transport, suggesting potential implications for synapse formation. Finally, we observed the dysregulated spine density in the animals with astrocyte specific TrkB.T1 deletion. These findings suggest that TrkB.T1 deficiency adversely affects normal astrocyte development, which in turn affects neuronal synapse development. These findings provide new insights into the expression mechanisms and functions of TrkB.T1 in astrocytes, enhancing our understanding of how these cells support brain health and function.

Thesis (MMed (Surgical Sciences. Orthopaedic Surgery))--University of Stellenbosch, 2010. / Objective: This research paper reports on the radiographic outcome of unstable thoracolumbar injuries with short segment posterior instrumentation as standalone treatment; in order to review rate of instrumentation failure and identify possible contributing factors. Background: Short segment posterior instrumentation is the treatment method of choice for unstable thoracolumbar injuries in the Acute Spinal Cord Injury Unit (Groote Schuur Hospital). It is considered adequate treatment in fracture cases with an intact posterior longitudinal ligament, and Gaines score below 7 (Parker JW 2000); as well as fracture dislocations, and seatbelt-type injuries (without loss of bone column - bearing integrity). The available body of literature often states instrumentation failure rates of up to 50% (Alanay A 2001, Tezeren G 2005). The same high level of catastrophic hardware failure is not evident in the unit researched. Methods: Sixty-five consecutive patients undergoing the aforementioned surgery were studied. Patients were divided into two main cohorts, namely the “Fracture group” (n=40) consisting of unstable burst fractures and unstable compression fractures; and the “Dislocation group” (n=25) consisting of fracture dislocations and seatbelt-type injuries. The groups reflect similar goals in surgical treatment for the grouped injuries, with reduction in loss of sagittal profile and maintenance thereof being the main aim in the fracture group, appropriately treated with Schantz pin constructs; and maintenance in position only, the goal in the dislocation group, managed with pedicle screw constructs. Data was reviewed in terms of complications, correction of deformity, and subsequent loss of correction with associated instrumentation failure. Secondly, factors influencing the aforementioned were sought, and stratified in terms of relevance. Results: Average follow up was 278 days for the fracture group and 177 days for the dislocation group (all patients included were deemed to have achieved radiological fusion – if fusion technique was employed). There was an average correction in kyphotic deformity of 10.25 degrees. Subsequent loss in sagittal profile averaged 2 degrees (injured level) and 5 degrees (thoracolumbar region) in the combined fracture and dislocation group. The only factor showing a superior trend in loss of reduction achieved was the absence of bone graft (when non-fusion technique was employed). Instrumentation complications occurred in two cases (bent connection rods in a Schantz pin construct with exaggerated loss in regional sagittal profile, and bent Schantz pins). These complications represent a 3.07% hardware failure in total. None of the failures were considered catastrophic. Conclusion: Short segment posterior instrumentation is a safe and effective option in the treatment of unstable thoracolumbar fractures as a standalone measure.

Neuroplasticity has been researched in many different ways, from the growing neonatal brain to neural responses to trauma and injury. According to recent research, neuroplasticity is also prevalent in the ability of the brain to repurpose areas that are not of use, like in the case of a loss of a sense. Specifically, behavioral studies have shown that deaf humans (Bavalier and Neville, 2002) and cats have increased visual ability, and that different areas of the auditory cortex enhance specific kinds of sight. One such behavioral test demonstrated that the dorsal zone (DZ) of the auditory cortex enhances sensitivity to visual motion through cross-modal plasticity (Lomber et. al., 2010). Current research seeks to examine the anatomical structures responsible for these changes through analysis of excitatory neuron dendritic spine density and spine head diameter. This present study focuses on the examination of DZ neuron spine density, distribution, and size in deaf and hearing cats to corroborate the visual changes seen in behavioral studies. Using Golgi-stained tissue and light microscopy, our results showed a decrease in overall spine density but slight increase in spine head diameter in deaf cats compared to hearing cats. These results, along with several other studies, support multiple theories on how cross-modal reorganization of the auditory cortex occurs after deafening

Sex differences in bone mass and size are thought to contribute to the greater incidence of vertebral fractures in women. While these sex differences are widely recognized, the relative contributions of bone mass, bone density, and bone size to the differences in vertebral strength and fracture risk between men and women have not been fully delineated. Furthermore, it is unknown whether the roles of each of these factors in determining vertebral strength change differently with age in men and women. We studied the bone content, density and geometry as well as vertebral loading and the factor of risk of the L3 vertebra in a sample of prepubertal males and females. Our first aim was to assess differences in vertebral bone dimensions, bone density, vertebral loading patterns and fracture risk, as measured by the factor of risk, in prepubertal children. Our second aim was to determine whether pre-pubertal growth affects the geometry and density of L3 differently in boys and girls. We measured vertebral dimensions, cross-sectional area and volumetric BMD of the third lumbar vertebral body in 93 prepubertal children (54 boys and 39 girls), using dual-energy X-ray absorptiometry scans obtained in the posterior-anterior and lateral projections. We also employed basic biomechanics to estimate vertebral loading during upright standing and forward bending. Bone strength and loading data were used to assess sex differences in the factor of risk in prepubertal children. Twenty children (11 boys and 9 girls) were assessed at baseline and seven months later to examine the effects of growth on bone size and vBMD. At baseline, boys and girls were similar for age, height, weight and calcium intake. L3 width and depth were 6.7% and 5.8% greater in boys than girls, respectively (P<0.001 and P=0.01, respectively). In contrast, vertebral height was 3.5% greater in girls than boys (P= 0.04). While vertebral loading was similar between sexes, stresses on the spine were 12.2% lower in boys during upright standing and 12.0% lower in boys during forward bending at both 50° and 90°, as compared to girls (P<0.001, P<0.01 and P<0.01, respectively). The factor of risk was similar between boys and girls under each loading condition. During growth, changes in vertebral size and density were not different between boys and girls. Our results indicate that even prior to puberty, sex differences in vertebral size contribute to differences in vertebral stress during standing and forward bending. Furthermore, before the onset of puberty, growth does not result in disparate changes between sexes. / Graduation date: 2004

There have been many advances in surgical residency education and similar interest exists in fellowship education. This study evaluated perceptions among spine surgeons about the specific competencies required for successful spine surgical fellowship training, and then compared these perceptions to clinical practice. Firstly, a questionnaire was administered to spine fellow trainees and academic spine surgeons across Canada in order to identify the cognitive and technical skills required for successful spine fellowship training. Fellowship trainees and supervisors had similar perceptions on the relative importance of specific cognitive and technical competencies. Differences in perceptions were found when comparing surgeons based on background residency specialty training (orthopaedic surgical or neurosurgical). Secondly, using administrative data, a retrospective study assessed volumes, surgeon characteristics, and outcomes for surgery of the degenerative lumbar spine in Ontario between 1995 and 2001. Neurosurgeons were found to perform more decompressions, and more total procedures, than orthopaedic surgeons with similar outcomes.

There have been many advances in surgical residency education and similar interest exists in fellowship education. This study evaluated perceptions among spine surgeons about the specific competencies required for successful spine surgical fellowship training, and then compared these perceptions to clinical practice. Firstly, a questionnaire was administered to spine fellow trainees and academic spine surgeons across Canada in order to identify the cognitive and technical skills required for successful spine fellowship training. Fellowship trainees and supervisors had similar perceptions on the relative importance of specific cognitive and technical competencies. Differences in perceptions were found when comparing surgeons based on background residency specialty training (orthopaedic surgical or neurosurgical). Secondly, using administrative data, a retrospective study assessed volumes, surgeon characteristics, and outcomes for surgery of the degenerative lumbar spine in Ontario between 1995 and 2001. Neurosurgeons were found to perform more decompressions, and more total procedures, than orthopaedic surgeons with similar outcomes.

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