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We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to beta cells ex vivo. Here we evaluate the role of Ngn3(+) cells in beta cell expansion in situ. PDL not only induced doubling of the beta cell volume but also increased the total number of islets. beta cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the beta cell expansion was attributable to proliferation of pre-existing beta cells. At sufficiently high Ngn3 expression level, upto 14% of all beta cells and 40% of small islet beta cells derived from non-beta cells. Moreover, beta cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing beta cells supporting a key role for Ngn3(+) insulin(-) cells in beta cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed beta cells as well as reprogramming of non-beta cells contribute to in vivo beta cell expansion in the injured pancreas of adult mice.

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Chronic tissue injuries present an enormous problem to both patients and healthcare professionals, and yet little is definitively known as to the underlying pathophysiology. While there are numerous comorbidities associated with these wounds, a unifying theme has been proposed to be the repetitive incidence of ischemia reperfusion injury.A mouse model of cyclic ischemia reperfusion was employed to examine the initiation events in the pathology of chronic wounds. Mice were subjected to eight hours of magnetic skin compression via four cycles of two-hours ischemia and thirty minutes of reperfusion. The presence of neutrophil markers of oxidative stress and inflammation such as myeloperoxidase and matrix metalloproteinases were measured at time points 1, 3, & 5 days post-injury. A sharp increase in MPO and MMP-9 was witnessed throughout, with the highest concentrations found at day 1. Simultaneously, immunodetection of heme oxygenase was performed, revealing high levels of inducible HO-I throughout the time course, with no change in HO-2 expression. Tissue damage was confirmed through histological examination.

Introduction: Soft Tissue Injuries (STIs) of the shoulder are common presentations to the Emergency Department but very little is known about the natural history, long-term disability or prognostic factors associated with these injuries. The goals of this pilot study are to describe the three-month outcome of these injuries, to begin to identify prognostic factors associated with poor outcome and to determine the feasibility of a future study aimed at predicting poor outcome. Methods: A cohort of 117 working-age adults presenting to the Emergency Department with acute STIs of the shoulder were prospectively recruited. Patients were interviewed by phone at one week, one month and three months. During the calls, patients completed the Disabilities of the Arm and Shoulder (DASH) questionnaire and provided information about treatments and follow-up that had occurred. Results: Of the 117 subjects, 72.3% had pain and disability above the population norm at one month and that number only decreased to 38.7% at three months. A substantial effect was also seen on Work and Leisure activities. The following prognostic factors were identified as having some association with poor three-month outcome: age, mechanism of injury, ability to rotate arm and abduct arm in ED, pain at one week, whether the injury was work-related, visit with family physician in first week and DASH score (disability) at one week. Conclusions: At the present time, the emergency physician must treat patients with STIs of the shoulder without any substantial knowledge of the morbidity that these injuries cause, which patients are at high risk of poor outcome or what would constitute optimum management. This study has determined that poor outcome is common and it has begun to identify factors that can help predict which patients will have a more complicated course. As it is now felt that the transition from acute to chronic pain begins well before three months, it will be important for future studies to develop a method of early identification of patients at high risk of poor outcome and to determine effective management in an attempt to prevent that transition. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2009-08-31 12:12:22.113

A majority of all fractures in current US armed conflicts are open fractures, in which a soft tissue injury is sustained along with the bone fracture. Even with gold standard treatment, in which muscle flaps are used to cover bony defects, patients often do not regain normal function of their extremity, highlighting the necessity for tissue engineering strategies for this complex clinical problem. Due to a substantial amount of tissue damage and debridement treatment in composite injuries, a large volume of cells and extracellular matrix (ECM) proteins that are necessary for tissue healing are removed from the body. In the replacement of large volumes of tissue, nutrient transfer necessitates a vascular supply to maintain the viability of delivered cells. The objective of this project was to examine the regenerative potential of engineered matrix constructs and stem cells on composite bone & muscle defects. We hypothesized that stem cells delivered on engineered matrix constructs into the muscle defect will aid in muscle regeneration and promote bone healing, ultimately resulting in superior functional limb recovery. These studies established multiple preclinical platforms for testing tissue engineering strategies as well as models that can be used to gain insights on the healing of VML and composite VML/bone defects. From some of the insights gained on the vascularization of the defect sites, a vascular treatment strategy was tested within these platforms and shown to have varying results in the treatment of complex multi-tissue injuries.

Deep tissue injury (DTI) is a severe form of pressure ulcers resulting from ischemia and mechanical damage due to unrelieved pressure. Despite many preventative methods, none so far has significantly reduced the incidence of DTI. The use of a novel method of pressure ulcer prevention, intermittent electrical stimulation (IES), was investigated. The current study investigated the effects of IES on surface pressure and tissue oxygenation in individuals with SCI. The results demonstrated that IES induced contractions caused significant reductions in pressure around the ischial tuberosities, as well as significant and sustained increases in oxygenation. Direct measurements of oxygen in an invasive rodent model indicated that IES induced contractions resulted in a 20-100% increase in tissue oxygenation. The results indicate that IES directly targets the pathogenic factors contributing to the development of pressure ulcers and thereby may be an effective method for the prevention of DTI.

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Please read the abstract in the section 00front of this document / Thesis (PhD (Medical Immunology))--University of Pretoria, 2008. / Immunology / unrestricted

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