Thesis (M.S.) -- Mississippi State University. Department of Industrial Engineering. / Title from title screen. Includes bibliographical references.

Thesis (Ph.D.)--Memorial University of Newfoundland, Faculty of Medicine, 2001. / Typescript. Bibliography: leaves 178-200.

Thesis (Ph. D.)--West Virginia University, 2010. / Title from document title page. Document formatted into pages; contains x, 178 p. : ill. Includes abstract. Includes bibliographical references.

It has been deduced from indirect evidence that significant adjustments of vascular resistance take place in the venous network when blood flow changes in a organ. In the following experiments, we attempted to test the hypotheses that changes in postcapillary resistance in skeletal muscle may be due to changes in venous diameter, changes in the number of venules with blood flow, and/or changes in the apparent viscosity of blood in venules. The hypotheses were tested by observing the response of cat sartorius muscle venules (7-200 μm diameter) during arterial pressure reduction and muscle contraction. There was no observable change in venular diameter during any of the above perturbations. There was a significant decrease in the already low normalized velocity of blood in venules from a mean of 13 sec⁻¹ under control conditions to 5 sec⁻¹ during arterial pressure reduction to 20 mm Hg. At very low pressures, the number of venules with blood flow decreased. Combining our findings with Lipowsky's (1975) in vivo viscometry data, it was predicted that resistance in venules would increase 100% as a result of increases in blood viscosity when blood flow was reduced 60%. During post-contraction hyperemia the normalized velocity of blood in venules increased from 16 sec⁻¹ to 38 sec⁻¹ and the number of venules with blood flow increased a modest amount. Combining our observations with Lipowsky's data, we predict that venular resistance would fall 54% when blood flow increased 250% If shear rate changes cause substantial changes in blood viscosity in venules as suggested by the findings cited above, hydrostatic pressure in the small venules should tend to remain relatively constant as flow is altered. To determine whether this is the case, pressures of venules were measured using the servo-null technique during arterial pressure reduction. Pressures in the larger venules were a linear function of blood pressure and blood flow with an intercept not significantly different from the systemic venous pressure. Pressures in the smallest venules studied (24 μm), however, were somewhat insensitive to alterations in blood pressure (intercept of 10.4 mm Hg) and blood flow (intercept of 13.2 mm Hg). The stability of pressure in 40 venules supports the hypothesis that variable blood viscosity maintains the pressure drop in the venous network and the capillary hydrostatic pressure somewhat constant during changes in blood flow.

published_or_final_version / abstract / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Human Systems Integration Report / Low back pain (LBP) and work-related musculoskeletal disorders (WMSDs) can lead to employee absenteeism, sick leave, and permanent disability. Over the years, much work has been done in examining physical exposure to ergonomic risks. The current research presents a new approach for assessing WMSD risk during lifting related tasks that combines traditional observational methods with video recording methods. One particular application area, the Future Combat System Medical Evacuation Vehicle (FCS MV-E) mockup, was chosen to illustrate the use of a twodimensional motion capture system. Combat medics (MOS 91W) who perform casualty evacuation under stressful battlefield conditions may be at risk for musculoskeletal injuries, which would reduce their ability to perform their job. The objective of this study is to demonstrate the use of video motion technology for posture analysis of team lifting and loading tasks. The results contribute to a determination of whether combat medics are at risk for WMSD due to awkward postures involved in the evacuation of litter casualties. Based on lessons learned from the current study, recommendations are offered to guide further research in motion analysis of manual material handling tasks.

In spite of its post mitotic nature, skeletal muscle maintains remarkable plasticity. Muscle fibres (myofibres) are capable of large alterations in their size as well as an enormous ability to regenerate following injury – thanks to a potent population of resident stem cells (satellite cells). Deciphering the molecular signalling networks responsible for skeletal muscle growth and regeneration is of key scientific interest – not least because of the therapeutic potential these pathways may hold for the treatment of diseases such as muscular dystrophy. In this thesis, the transcriptional co-factor Yes-Associated protein (Yap), the downstream effector of the Hippo Pathway, was investigated in skeletal muscle. Using gain and loss of function approaches within in vitro, ex vivo and in vivo models, the contribution of Yap in regulating both satellite cell behaviour and myofibre growth was investigated. Yap expression and activity are dynamically regulated during satellite cell activation, proliferation and differentiation ex vivo. Overexpression of Yap increased satellite cell proliferation and maintained cells in a ‘naive’, ‘activated’ state by inhibiting myogenic commitment. Knock-down of Yap impaired satellite cell expansion, but did not influence myogenic differentiation. Yap interacts with Tead transcription factors in myoblasts to upregulate genes such as CyclinD1 and Myf5. Forced expression of Yap eventually led to the oncogenic transformation of myoblasts in vitro. Contrary to predictions, constitutive expression of Yap under an inducible muscle-specific promoter in adult mice failed to induce growth and instead led to muscle wasting, atrophy and degeneration – providing evidence against the notion that Yap represents a universal regulator of tissue growth. These data provide the first insight into the function of Yap in skeletal muscle. Results highlight a novel role for Yap in regulating myogenic progression in satellite cells, as well as its propensity to induce oncogenic transformation. The precise function of Yap in adult myofibres remains unclear however, data presented here demonstrates clear cell-type specific roles for Yap compared to observations made in other tissues.

Ligament and tendon injuries remain a persistent clinical challenge, accounting for up to 45% of the 32 million musculoskeletal injuries reported in the U.S. each year. However, current soft tissue repair and reconstruction techniques are limited by insufficient integration with subchondral bone, potentially leading to graft failure and suboptimal functional outcomes. Therefore, there is a pressing clinical need for functional solutions that can enable integrative soft tissue reconstruction via regeneration of the fibrocartilaginous insertion present at the junction between bone and major ligaments and tendons. This fibrocartilaginous enthesis consists of compositionally distinct but structurally continuous tissue regions (non-calcified and calcified fibrocartilage), and it plays a critical role in mediating complex load transfer between soft tissue and bone while minimizing the formation of stress concentrations at the insertion. Given the functional significance of the insertion site and using the anterior cruciate ligament (ACL) as a model tissue, the objective of this thesis is identify and optimize tissue engineering strategies for regeneration of the fibrocartilaginous interface. Thus, the studies detailed in this thesis consist of elucidation of key interface characteristics that can inform interface scaffold design, identification of an optimal cell source, and optimization of chemical and physical stimuli for fibrocartilage formation. To guide biomimetic scaffold design, this thesis began with quantitative mapping of the compositional and structural properties of the native ligament-to-bone interface. As both the aligned collagen matrix structure and distinctive mineral distribution pattern across the insertion were shown to be highly conserved over time, an ideal scaffold for fibrocartilage interface regeneration should therefore consist of aligned fibers and must be able to support the formation of both non-mineralized and mineralized fibrocartilage tissues. Additionally, evaluation of ex vivo behavior of insertion fibrochondrocytes cultured on aligned nanofiber scaffolds indicated that an ideal system for fibrocartilage regeneration should also support cell-mediated deposition of both types I and II collagen as well as proteoglycans. Comparison of potential cell sources for fibrocartilage tissue engineering showed that synovium-derived mesenchymal stem cells (SDSCs) exhibited higher proliferative and fibrochondrogenic differentiation potential compared to bone marrow-derived mesenchymal stem cells. Thus, subsequent studies focused on optimization of culture parameters for SDSC-mediated fibrocartilage formation. Nanofiber scaffolds that provided controlled release of transforming growth factor (TGF)-β3, which is known to play a critical role in development of the insertion as well as in scarless healing, were developed to guide SDSC differentiation. Scaffold-mediated TGF-β3 delivery enhanced cell proliferation and matrix synthesis in a dose-dependent manner, resulting in synthesis of fibrocartilaginous matrix consisting of both type I and II collagen as well as proteoglycans. As mechanical loading is known to also play a critical role in insertion development, a custom bioreactor that mimics the complex loads sustained at the interface was also developed. It was shown that the bioreactor simultaneously generated both tensile and compressive stresses and modulated SDSC matrix synthesis, where deposition of fibrocartilaginous matrix was observed on mechanically loaded scaffolds without any additional chemical co-stimulation. Finally, as a functional scaffold for integrative ACL repair must support the establishment of both non-mineralized and mineralized tissue regions, the combined effects of TGF-β3 and hydroxyapatite (HA) on MSC-mediated formation of mineralized fibrocartilage were also explored. The addition of HA nanoparticles to the scaffold was shown to enhance cell proliferation and matrix synthesis and represents a promising strategy for formation of mineralized fibrocartilage. Collectively, these observations delineate the importance of bioinspired chemical and physical stimuli in fibrochondrogenic differentiation, and how they can be optimized for stem cell-mediated interface regeneration. These studies yield valuable scaffold design criteria and establish in vitro culture parameters that can be applied to functional integration of soft connective tissue with bone at various critical attachments throughout the musculoskeletal system, including the ligament and tendon-to-bone entheses, as well as for regeneration of other important fibrocartilaginous tissues.

Work-related musculoskeletal disorders (WMDs) are a major public health problem in terms of the considerable amount of disability, impairment, and associated economic cost. Among these disorders, the occurrence of WMD symptoms of the neck is prevalent and has been associated with significant disability, long periods of sick leave and loss of productivity in occupational settings. Risk factors for WMDs are multifactorial, and studies have typically focused on ergonomic factors. Psychosocial factors in the work environment have been recently considered; however, findings across these studies have not been consistent. Despite the evidence associated with ergonomic factors on the occurrence of WMDs, widespread prevention and treatment efforts have not been successfully implemented. Psychosocial factors such as high psychological demands, low decision latitude and low social support may play a role in WMD occurrence. The demand-control-support model has been widely used to predict job strain. Particularly for disorders of the neck, job strain seems to play a strong role in their occurrence. The psychosocial work environment and WMDs are listed as research priorities of the National Occupational Research Agenda developed by the National Institute for Occupational Safety and Health. This cross-sectional study looked at job strain and neck symptoms, while controlling for confounders. This project was carried out on a group of semiconductor manufacturing workers. The prevalence of neck symptoms was measured by a self-administered questionnaire. A Chinese version of the Job Content Questionnaire was included to assess psychosocial factors and to test the demand-control-support model. An observational checklist was developed and used to assess ergonomic exposures on individual workers' jobs. The participation rate was 86.5%. The final sample of semiconductor workers consisted of 373 female participants. Their mean age was 28.4 years ranging from 18 to 41 years. The mean length of employment was 4.3 years. The prevalence of symptoms of neck disorders in the semiconductor manufacturing population was 23.9%. It was concluded that the prevalence rates of neck symptoms of WMDs in this study were high, especially given the very conservative outcome definition that was used. The study findings partially supported the job strain model, showing an increase in prevalence of neck symptoms with psychological and physical job demands; however, association with decision latitude and social support were not supported. Further studies with more comprehensive measurements of work-related psychosocial factors are implicated and effective prevention strategies for neck symptoms of WMDs are suggested.

The purpose of this investigation was to determine the effects of two speeds of isokinetic training on muscular strength, power and endurance on college females. The study involved thirty college females. Twenty of the subjects who served in the experimental groups were randomly assigned to one of two groups: fast speed or slow speed group. This was done after matching based on the pretest strength measure. Ten subjects who served as the control group were from a bowling class This investigation was conducted for seven weeks with a training frequency of three days per week. The experimental treatment was isokinetic training for right and left knee extensions. There were three sets of repetitions; each set lasted twenty seconds with a thirty second rest period between each set. The dependent variables measured were strength, Power I, Power II and muscular endurance for the right and left knee extension. Analysis of variance was used to determine differences between the groups on pretest measures. A comparison of the pretest and posttest means was made to determine differences resulting from training. Analysis of covariance was used for the posttest measures with pretest measures as covariates for the eight dependent variables. Results of statistical analysis indicated that no significant differences existed on the pretest treasures between the three groups in the eight variables with the exception of Power I for the right knee and endurance measure for the left knee extension. Posttest analysis revealed significant differences in all the eight dependent variables between the experimental groups and the control group. Also, significant differences existed between the fast speed and the slow speed groups for six of the eight variables. There were no significant differences on the strength measures between the experimental groups. The isokinetic training method was found to be effective in developing strength, power and muscular endurance. Also, the isokinetic fast speed was found to be a more effective way of bringing about power and muscular endurance development.