Unintentional injuries are the leading cause of death for children aged 5-19 Twenty-two million children are injured each year and approximately one quarter of these injuries occur on school premises. Schools must provide nursing services to children who attend school, but ratios of registered nurses to students is higher than the 1:750 recommended ratio. Current school teachers believe pre-service teachers should be trained in emergency care in teacher training programs. Yet, no research has been conducted to evaluate pre-service teachers’ knowledge and attitudes toward emergency care. The purpose of the study was to investigate pre-service teachers’ knowledge of and attitude toward emergency care in the school setting. A cross sectional group-comparison survey design was used. A 40-item questionnaire was administered to pre-service elementary teachers at Ball State University located in Muncie, IN. The questionnaire consisted of questions from “Emergencies in the school setting: Are public school teachers adequately trained to respond?” and Urban public school teachers’ attitudes and perceptions of the effectiveness of CPR and automated external defibrillators. Sub-group comparisons were made using bivariate and multivariate analyses of similar demographic, attitude, and knowledge questions. Findings indicated that pre-service teachers have a positive attitude toward emergency care, low levels of knowledge about emergency care, and a low level of willingness to provide emergency care in schools. In addition, when comparing pre-service teachers who had received emergency care training to those who did not, a statistically significant difference was found in their knowledge about emergency care. Emergency care training has limited influence on pre-service teachers’ attitudes and willingness to provide care. / Department of Physiology and Health Science

Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008

Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008

Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008

Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008

Post-traumatic osteoarthritis (PTOA) of the knee is a complication resulting from direct injury to the joint, such as anterior cruciate ligament and meniscus tears, and accounts for approximately 12% of all OA cases. The economic and clinical impact of PTOA is also greater than idiopathic OA, as patients are younger and often more active, requiring treatments for symptomatic OA over a greater fraction of their lifetime. A common strategy to manage pain and inflammation associated with PTOA is the intraarticular administration of corticosteroids. However, these injections are limited due to the requirement of high-doses imposed by synovial joint clearance rates and their resulting systemic side effects. In addition, currently used broad-spectrum corticosteroids are palliative and not curative, stemming from incomplete knowledge of specific mechanisms that drive cartilage degeneration and other joint pathologies. Thus, most patients with PTOA eventually undergo surgical procedures such as osteochondral graft transplantation for focal defects and in more severe cases, total knee arthroplasty. As such, the studies presented in this dissertation (i) offer specific insights into mechanisms by which traumatic injury can drive joint degeneration and (ii) present novel strategies to modulate joint responses to pathological factors by leveraging sustained drug-delivery platforms. In Part I, mechanistic assessments of human cartilage and synovium responses to insults are conducted to identify novel pathways that may lead to impaired joint homeostasis. First, a direct consequence of traumatic injury, hemarthrosis, is explored as a potential contributor to the development of PTOA specifically through contributions by red blood cells. We demonstrate for the first time the differential roles of erythrocytes in their intact and lysed states through measures of oxidative stress and changes to metabolomic profiles in the context of ferroptosis. Furthermore, we demonstrate the therapeutic potential of Ferrostatin-1, a lipophilic radical scavenger in inhibiting pathological changes to cartilage and its crosstalk with the neighboring synovium in an in vitro model of hemophilic arthropathy. Second, a strategy to prevent an indirect consequence of traumatic injury, arthrofibrosis, is presented in an in vitro model of joint contraction. Fibrosis and the presence of hyperplastic synovium are implicated in the progression of OA through pathological shifts in tissue composition as well as secreted factors that promote cartilage degeneration and the maintenance of a pro-inflammatory joint environment. A type I transforming growth factor beta-1 receptor inhibitor, SB-431542, is encapsulated in polymeric microspheres for the prophylactic treatment of arthrofibrosis through sustained low-dose drug delivery to circumvent the challenges associated with resident joint clearance rates. Utilizing human-based in vitro models of cartilage and synovium pathology, we present novel mechanisms and therapeutic strategies to prevent pathological changes following traumatic joint injury that may contribute to the development of PTOA. In Part II, the sustained delivery platform introduced in Part I is extended to the treatment of PTOA. Osteochondral graft transplantation is currently the clinical gold standard for large focal cartilage lesions. However, allograft procedures are limited due to the lack of available donor tissues and autografts are associated with complications due to donor-site morbidity. In both cases, grafts are subject to failure, potentially in part due to the continual presence of pro-inflammatory factors following surgical procedure. In this section, we present cellular agarose hydrogels embedded with dexamethasone-releasing microspheres that are integrated with a titanium base as a functional tissue-engineered alternative to native osteochondral allografts. These allogenic tissue-engineered grafts were assessed in an in vivo preclinical canine model in their ability to maintain clinical function and to modulate the inflammatory response over the course of 12 months. We successfully demonstrated the feasibility of using engineered grafts by comparing clinical measures of range of motion, function, lameness, and pain, as well as modified cartilage graft scores, against native osteochondral allograft controls. In addition, improvements in the histopathological scoring of neighboring synovial and meniscal tissues indicate the therapeutic capacity of dexamethasone released from within the joint to modulate the inflammatory response up to one-year post-implantation. Taken together, the studies presented in this dissertation identify novel mechanisms behind pathological changes to the cartilage and synovium that may contribute to the development of PTOA following injury. Potential therapeutic targets, inhibitory compounds, and delivery strategies are also assessed using human-based in vitro models of disease and further validated in an in vivo canine model through a clinically relevant timeframe. Ultimately, we demonstrate for the first time, the use of dual-function tissue-engineered grafts in a weight-bearing region of the knee joint to circumvent limitations associated with the clinical gold standard for the treatment of large focal cartilage defects.

Thesis (MSc)--University of Stellenbosch, 2007. / ENGLISH ABSTRACT: Human studies on the response of muscle to contusion injury are limited, probably due to the large variability in injury severity and the non-specificity of clinical symptoms reported. To circumvent this problem, several experimental animal models have been designed to study muscle damage and regeneration after contusion injuries. However, the majority of techniques currently used to induce contusion injury are very invasive and therefore not optimal. Furthermore, published studies regarding clinical treatment of such injuries are limited. The main aims of this study were therefore: a) to establish and characterise an in vivo model of non-invasive contusion injury, and b) to assess the effect of pre-injury chronic administration of the antioxidant supplement Oxiprovin™ - a natural grape seed extract (GSE) - on skeletal muscle recovery after experimentallyinduced injury. Two groups of male Wistar rats were subjected to 14 days of oral administration of isovolaemic placebo (sterile isotonic saline) or GSE (20 mg/kg/day) prior to induced contusion. Contusion injury was induced with the mass-drop technique, and recovery parameters assessed for up to 14 days post-injury. Placebotreated rats on average exhibited a 56 % higher creatine kinase (CK) activity when compared to the GSE-treated rats when area under the curve (AUC) was calculated for 14 days post-injury (p < 0.001). In the placebo group, plasma oxygen radical absorbance capacity (ORAC) was unchanged over time, but muscle ORAC was significantly increased by day 7 post-injury (p < 0.001). In the GSE group, a significant decrease in both plasma (p < 0.01) and muscle ORAC (p < 0.001) was evident 4 hr after injury, followed by a significant increase by day 3 (p < 0.05 and p < 0.001 respectively). CD34+ satellite cell (SC) numbers (quiescent and activated) peaked earlier in GSE-treated rats when compared to placebo-treated rats (4 hours vs. day 7 post-injury). Total satellite cell number (CD56+) also peaked earlier in GSE-treated rats than in placebo-treated rats (4 hours vs. 3 days post-injury), while M-cadherin+ SC numbers (quiescent, activated or proliferating) in both treatment groups were significantly increased 4 hours post-injury (p < 0.001), but more so in the placebo group. In GSE-treated rats when compared to placebo-treated rats, newly generated muscle fibres (displaying central nuclei and MHCf +) both appeared (day 3 vs. day 7 post-injury) and peaked in number (day 3 vs. day 7 post-injury; increase from baseline p < 0.001 for both) earlier. The results of this study demonstrate that we have successfully established an in vivo model for non-invasive contusion injury in rats. Furthermore, we have shown that Oxiprovin™: a) increased the ability to scavenge reactive species generated after injury and b) resulted in the activation of satellite cells and formation of newly generated muscle fibres at an earlier time point, thus accelerating the recovery of skeletal muscle after a standardised contusion injury. / AFRIKAANSE OPSOMMING: Eksperimente aangaande die reaksie van spier op kneusings in mense is beperk, waarskynlik as gevolg van die groot verskeidenheid simptome wat mag voorkom en die verskille in die ernstigheid van beserings. Ten einde hierdie problem te oorbrug, is verskeie eksperimentele diermodelle opgestel om kneusings en die herstel van spier daarna te ondersoek. Die tegnieke wat grootendeels vandag gebruik word om kneusings te veroorsaak, maak inbraak op die spier deur die spier te ontbloot voor besering, en is dus nie ideaal nie. Daar is ook nie baie bewyse aangaande die mees geskikte manier om so ‘n besering klinies te behandel nie. Die doel van hierdie studie was dus om: a) ‘n in vivo model van kneusings op te stel en te omskryf, en b) die effek van chroniese toediening van die antioksidant Oxiprovin™ - ‘n natuurlike druifsaad ekstrak (DSE) – op die herstel van skeletspier na ‘n kneusing te ondersoek. Twee groepe manlike Wistar rotte is onderwerp aan mondelikse toediening van isovolemiese plasebo (steriele isotoniese soutoplossing) of DSE (20 mg/kg/dag) vir ‘n tydperk van 14 dae voor kneusing. Kneusing is geïnduseer met die “massdrop” tegniek, en parameters van herstel is ondersoek tot en met 14 dae na besering. Plasebo-behandelde rotte het gemiddeld 56 % hoër kreatien kinase (KK) aktiwiteit in vergelyking met DSE-behandelde rotte (p < 0.001), toe die oppervlak onder die kurwe (OOK) tot en met 14 dae na besering bereken is. Geen verskil oor tyd is in die plasebo groep opgemerk toe plasma suurstof radikaal absorpsie kapasiteit (SRAK) bepaal is nie, maar ‘n betekenisvolle toename in spier SRAK teen dag 7 (p < 0.001) is waargeneem. ‘n Betekenisvolle afname in beide plasma (p < 0.01) en spier (p < 0.001) SRAK van die DSE is teen 4 hr waargeneem, gevolg deur ‘n betekenisvolle toename teen dag 3 na besering (p < 0.05 en p < 0.001 onderskeidelik). Die aantal CD34+ satelliet selle (SS – rustend en geaktiveerd) het beduidend vroeër in die DSE groep gestyg in vergelyking met die plasebo groep (4 uur vs. 7 dae na besering). Die totale aantal SS (CD56+) het ook vroeër in die DSE-behandelde rotte as die plasebobehandelde rotte gestyg (4 uur vs. 3 dae na besering), terwyl die aantal Mcadherin+ SS (rustend, geaktiveerd of prolifererend) betenisvol gestyg het in beide groepe teen 4 uur (p < 0.001) na besering, maar hoër in die plasebo groep was. Die aantal nuutgevormde spiervesels (met sentraal geleë nukleï en MHCf +) het beide vroeër verskyn en gepiek in die DSE-behandelde rotte in vergelyking met die plasebo-behandelde rotte (dag 3 vs. dag 7 na besering). Die resultate van hierdie studie dui aan dat ons instaat was om ‘n in vivo model van nie-indringende kneusing in rotte op te stel. Verder, het ons ook bewys dat Oxiprovin™ toediening die vermoë verleen het om: a) reaktiewe spesies wat na beserings gevorm word, meer doeltreffend te verwyder en b) satelliet selle vroeër te aktiveer en die vorming van nuwe skeletspiervesels te vervroeg, om sodoende die herstel van skeletspier na ‘n gestandardiseerde kneusing vinniger te bewerkstellig.

Aim The aims of this project were to (i) evaluate whether the trauma care system established in Hong Kong has improved the survival rate among trauma patients; (ii) evaluate the effectiveness of trauma teams and their coordinators, primary trauma diversion, and performance improvement programmes, and assess the influence of gender and age on patient outcomes; and (iii) compare clinical outcomes before and after the establishment of a trauma system in Hong Kong and measure them against those achieved in an established regional trauma system in Australia. / Background Injury is a major public health problem that creates an enormous social burden. Although Hong Kong has tried to build up a trauma care system according to the criteria employed by the American College of Surgeons Committee on Trauma, there are a number of differences between the two. The effectiveness of the key components of trauma care processes and their clinical outcomes are unclear, and the final outcome in terms of survival rate is unknown. / Conclusion Proficient trauma teams, primary trauma diversion, and clinical guidelines are key components of the trauma system that contribute to improved outcomes. / Methods Retrospective analysis of data collected prospectively from the trauma registries in Hong Kong and Australia. The Trauma and Injury Severity Score (TRISS), the W score, the Z score, the M score, and Ws statistics are employed to evaluate the mortality rate. / Results The W score for Hong Kong improved significantly from - 4.79 in 1997 to 0.51 in 2009 after the trauma system was established (P&lt;0.05). The improving trend observed in the Ws score (- 4.86 +/- SE 1.24 Vs 1.06 +/- SE 0.74) over the same period indicates that the survival rate increased from 1997 to 2009 (P &lt; 0.01). The time taken to deliver the patient from the scene to definitive care was reduced by 97 minutes (P &lt; 0.001) using a primary trauma diversion strategy. Proficient trauma teams are associated with reduced mortality in patients with a moderately poor probability of survival (p = 0.007) and trauma nurse coordinators play an essential role in conducting trauma audits and maintaining trauma registries. The introduction of guidelines and staff education could result in significant improvements to the trauma care process. Advancing age is associated with an increased mortality rate, whereas gender is not. Injury prevention programmes in Hong Kong are inadequate. / Yeung, Hiu Hung. / Advisers: Timothy H. Rainer; Wai Sang Poon. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 282-328). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Approximately 2 to 3 million people in the United States suffer from chronic wounds, which are defined as wounds that do not heal in 30 days time; an estimated $25 billion per year is spent on their treatment in the United States. In our work, we focused on treating chronic wounds with bacterial infections using hyperbaric and topical oxygen therapies. We used a mathematical model describing the interaction between bacteria, neutrophils and oxygen. Optimal control theory was then employed to study oxygen treatment strategies with the mathematical model. Existence of a solution was shown for both therapies. Uniqueness was also shown for hyperbaric therapy. We then used a forward-backward sweep method to find numerical solutions for the therapies. We concluded by putting forth ideas for how this problem could progress toward finding applicable treatment strategies.

Thesis (PhD (Physiology (Human and animal))-- University of Stellenbosch, 2007. / Definition: Stem cells are unspecialised cells with the capacity for long-term self-renewal and the ability to differentiate into multiple cell-lineages. The potential for the application of stem cells in clinical settings has had a profound effect on the future of regenerative medicine. However, to be of greater therapeutic use, selection of the most appropriate cell type, as well as optimisation of stem cell incorporation into the damaged tissue is required. In adult skeletal muscle, satellite cells are the primary stem cell population which mediate postnatal muscle growth. Following injury or in diseased conditions, these cells are activated and recruited for new muscle formation. In contrast, the potential of resident adult stem cell incorporation into the myocardium has been challenged and the response of cardiac tissue, especially to ischaemic injury, is scar formation. Following muscle damage, various growth factors and cytokines are released in the afflicted area which influences the recruitment and incorporation of stem cells into the injured tissue. Transforming Growth Factor-β (TGF-β) is a member of the TGF-β-superfamily of cytokines and has at least three isoforms, TGF-β1, -β2, and -β3, which play essential roles in the regulation of cell growth and regeneration following activation and stimulation of receptor-signalling pathways. By improving the understanding of how TGF-β affects these processes, it is possible to gain insight into how the intercellular environment can be manipulated to improve stem cell-mediated repair following muscle injury. Therefore, the main aims of this thesis were to determine the effect of the three TGF-β isoforms on proliferation, differentiation, migration and fusion of muscle progenitor cells (skeletal and cardiac) and relate this to possible improved mechanisms for muscle repair. The effect of short- and long-term treatment with all three TGF-β isoforms were investigated on muscle progenitor cell proliferation and differentiation using the C2C12 skeletal muscle satellite and P19 multipotent embryonal carcinoma cell-lineages as in vitro model systems. Cells were treated with 5 ng/mℓ TGF-β isoforms unless where stated otherwise. In C2C12 cells, proliferating cell nuclear antigen (PCNA) expression and localisation were analysed, and together with total nuclear counts, used to assess the effect of TGF-β on myoblast proliferation (Chapter 5). The myogenic regulatory factors MyoD and myogenin, and structural protein myosin heavy chain (MHC) were used as protein markers to assess early and terminal differentiation, respectively. To establish possible mechanisms by which TGF-β isoforms regulate differentiation, further analysis included determination of MyoD localisation and the rate of MyoD degradation in C2C12 cells. To assess the effect of TGF-β isoforms on P19 cell differentiation, protein expression levels of connexin-43 and MHC were analysed, together with the determination of embryoid body numbers in differentiating P19 cells (Chapter 6). Furthermore, assays were developed to analyse the effect of TGF-β isoforms on both C2C12 and P19 cell migration (Chapter 7), as well as fusion of C2C12 cells (Chapter 8). Whereas all three isoforms of TGF-β significantly increased proliferation of C2C12 cells, differentiation results, however, indicated that especially following long-term incubation, TGF-β isoforms delayed both early and terminal differentiation of C2C12 cells into myotubes. Similarly, myocyte migration and fusion were also negatively regulated following TGF-β treatment. In the P19 cell-lineage, results demonstrated that isoform-specific treatment with TGF-β1 could potentially enhance differentiation. Further research is however required in this area, especially since migration was greatly reduced in these cells. Taken together, results demonstrated variable effects following TGF-β treatment depending on the cell type and the duration of TGF-β application. Circulating and/or treatment concentrations of this growth factor could therefore be manipulated depending on the area of injury to improve regenerative processes. Alternatively, when selecting appropriate stem or progenitor cells for therapeutic application, the effect of the immediate environment and subsequent interaction between the two should be taken into consideration for optimal beneficial results.