Traditional Chinese medicine has a long history of using plants therapeutically including multiple species of the genus Rubus (Rosaceae). Fruits and other parts of Rubus plants have had a significant effect on human health and nutrition in both ancient and modern times. The pharmacological effects of Rubus include anti-inflammatory, antibacterial, anti-stress, anti-cancer and anti-aging properties. One of the current challenges limiting further development of Rubus resources in traditional Chinese medicine is a poor understanding of phylogenetic relationships among Rubus species in general and especially among Asian species, and also the need for additional studies of phytochemicals. Several confounding factors are frequent hybridization, polyploidy, and highly variable morphology due in part to diverse ecological conditions across species’ distributions. The goal of this study was to elucidate phylogenetic relationships among Rubus species in the predominantly Asian subgenera Idaeobatus and Malachobatus emphasizing species valued in traditional Chinese medicine. Sequences of six noncoding (plus matK) chloroplast DNA regions totaling 8,276 aligned characters were analyzed for 35 Rubus species using maximum parsimony (MP) and maximum likelihood (ML). Both analytical approaches yielded topologically identical phylogenies except for one additional grouping in the ML tree. The phylogeny has nearly complete resolution and divides the species into two primary clades; one comprises R. geoides (representing the Southern Trans-Pacific clade), R. nivalis (subg. Chamaebatus) and R. trivialis (representing subg. Rubus) and the other is composed largely of R. arcticus and R.saxatilis (subg. Cylactis), and the large subgenera Idaeobatus (raspberries) and Malachobatus. Within the latter, principally Asian clade, three unresolved lineages exist (four using MP) precluding an improved understanding of the relationships among them. However, three major subclades containing Asian species have good support. Two contain subg. Idaeobatus species only, and the third comprises members of the exclusively polyploid subgenera Malachobatus and Dalibardastrum. Examination of the presence of biochemically active terpenes reveal that triterpenes are common among subg. Idaeobatus species with diterpenes reported only in R. pungens and R. chingii (not sampled). Subg. Malachobatus species have not been as thoroughly investigated so triterpenes may also be common in these species. From these results, multiple subg. Idaeobatus and subg. Malachobatus species may be good candidates for terpene analysis as members of their respective clades possess triterpenes. Moreover, five species not currently used in traditional Chinese medicine should be evaluated as they also occur in China, and may possess medicinal value.

The inflammatory process is a critical component of the repair and regeneration of skeletal muscle following injury. The influx of innate immune cells following injury is intricate, and temporal nature. Although required for proper repair and regeneration, the inflammatory process has been shown to exacerbate initial damage, prolonging the healing process. Complementary Alternative Medicine (CAM) treatments, such as massage therapy, are a promising substitute for pharmaceutical modulation of the inflammatory response, and recent studies into the efficacy of massage have begun to report the physiological benefits of massage application following injury. Nonetheless, there is a significant lack of sound mechanistic investigations into massage application and its effects on unperturbed tissue. To gain insight to its potential influences on healthy skeletal muscle, massage was applied at three different magnitudes of load in vivo. Using a custom fabricated device for cyclic compressive loading, Wistar rats receiving massage had an increased expression in genes associated with the immune response; a significant change in the macrophage populations within the muscle tissue; and demonstrated a systemic effect marked by the increase of immune cells in the non-massaged limb. Further elucidating the systemic and immunomodulatory effects of massage, Long Evans rats receiving non-constrained eccentric exercise followed by a single 30minute bout of massage, displayed a significant crossover effect just 6 hours post exercise through the modulation of inflammatory cells in the non-massaged limb. Together these investigations suggest that mechanotransductive properties of massage can promote modulation of the immune response absent of pharmaceuticals.

Music is a powerful modality that can bring about changes in individuals of all ages. This research employed both an experimental and quasi-experimental design to identify the effects of music as it influenced psychological well-being, memory, and cognition among older adults. Specifically, it addressed three aims: (a) To determine to what extent learning to play a music instrument later in life influenced psychological well-being and cognitive function of non-institutionalized healthy seniors, (b) To determine the effects of the amount of music involvement on psychological well-being and cognitive function (c) To determine the benefit of music for those with limited/no music experience. For the first aim, it was hypothesized that individuals in the experimental music group would maintain and/or improve psychological well-being, memory, and cognitive function more than those assigned to the wait-list control group. For the second aim, it was hypothesized that participants with extensive music involvement would have higher scores on cognitive ability measures and experience greater psychological well-being than those who had not been actively involved in music throughout their life. For the third aim, it was hypothesized that the participants with limited/no music involvement throughout their life would have a larger change on the psychological well-being measures and cognitive assessments than those who had more music involvement. For the experimental portion (Aim 1), the study employed a 6-week music intervention with non-institutionalized older adults. The quasi-experimental portion (Aims 2 & 3) divided participants according to their amount of time involved in music and then looked at psychological well-being and cognitive function. This dissertation did not show a strong connection between music, memory, and cognition so it did not achieve the desired overall results. However, the findings did suggest that music may modify some areas of cognitive function (verbal learning, memory, and retention) and psychological well-being but did not influence other areas (playing a music instrument for any length of time). Therefore, the findings of this dissertation can be a basis upon which future research relating to music, cognitive functioning, psychological well-being and involvement in music can build.

Although most “alternative” medical practices have existed far longer than conventional healthcare, modern allopathic continues to be the dominant system of medicine used in the United States. Herbal medicine is one of the oldest healing practices known to humankind and continues to be practiced today despite the numerous challenges modern society poses. As Julie Stone and Joan Mathews illuminate in Complimentary Medicine and the Law, “Plant-based remedies have been the principal source of medicines in healing traditions around the world and, as the World health Organization is at pains to remind us, 80 percent of the world’s population still depends primarily on plant medicine." Another statistic cited by Larry Dossey in Reinventing Medicine illustrates, “…researchers have found that adverse reactions to drugs kill over 100,000 people a year in US hospitals. That is the equivalent of a passenger jet crashing everyday. If this level of death were seen in any other field, it would probably be considered a national scandal." These facts reveal that American citizens have come to believe in a form of healthcare that is not widely accepted by the rest of the world, and that has some surprisingly dangerous characteristics hidden within. The question thus arises as to why biomedicine continues to be the standard form of healthcare in the US, and why alternative forms of medicine are devalued and failed to be justifiably recognized and incorporated into treatment strategies.

This research investigated the transformative and extraordinary experiences of nurse healers. The broad aim of the research was to promote the role of the healer in nursing by providing data on the experiences specific to nurse healers’ evolution as healers. The research was theoretically informed by van Manen (1990, 1984) and utilised hermeneutic phenomenology. Van Manen’s emphasis on writing as the key element of phenomenology in lived experience research was employed to bring forth a sense of lived immediacy and aesthetic colour essential to phenomenological understanding. The thesis was also theoretically aligned with the conceptual model of nursing as a caring-healing profession, developed by Jean Watson (1999, 1990a, 1988, 1985a). In particular, this research drew on Watson’s explicit connection of nursing with healing and nursing practice with transformational, transpersonal and esoteric insights. There were eleven nurse (nine women and two men) participants in the study. All participants identified strongly as healers. Selection was based on how long, and important to the individual was their commitment to being a healer. The data collection method used was semi structured interview with a predominant focus on storytelling. The overarching theme of ‘Walking Two Worlds’ was identified, and within that five essential themes were uncovered: (1) Belonging & Connecting; (2) Opening to Spirit; (3) Summoning; (4) Wounding & Healing Journey; and (5) Living as a Healer. Implications for nursing discussed include the need for the profession to provide support to nurse healers as they encounter challenging experiences and to allow for ontological flexibility regarding the esoteric aspects of human/spiritual experience revealed by this research. Further the need to extend the understanding invoked by healing beyond the obvious and opening vistas into experience which have been previously repudiated by domineering, narrow and spirit-denying powers in our society is also discussed.

This thesis is about the contemporary challenges facing herbal medicine. Specifically it concerns the difficulties faced by Australian herbalists in their attempts to maintain authority over the knowledge base of their craft and a connection with traditional understandings of the uses of plant medicines, while at the same time engaging with biomedicine and the broader Australian healthcare system. It contributes to the study of the nascent field of qualitative studies in contemporary western herbal medicine by making three main arguments.Firstly, Australian herbal medicine is characterised by its origins as a European colonial practice and its history of professional marginalisation during most of the 20th century. Secondly herbal practitioners have been unable to capitalise significantly on a surge of public popularity in the closing years of the 20th century which brought with it the interest of industry, the scrutiny of regulators and the renewed attention of biomedicine. Herbalists continue to struggle for recognition in the face of these more powerful interests. Thirdly it is argued that herbalists are attempting to gain legitimacy and acceptance as a healthcare profession through a process of underpinning their knowledge base with science, which is replacing their traditional philosophical basis. This has the effect of weakening the ability of herbalists to maintain their identity as an independent profession and makes its knowledge base vulnerable to appropriation by other healthcare professions.Gross’ model of the cultural location of traditions in contemporary societies is used to clarify the situation of herbalists and to identify problems consequent to the political choices they have made or which have been forced upon them. Gross suggests that traditions which place themselves close to power have difficulty in maintaining their own character and integrity, but that other cultural locations are also problematic and limit full participation in society. vi It is argued that there are compelling reasons to move beyond Gross’ analysis and to find ways to strengthen the independence of the herbal profession. Given the financial problems facing the current healthcare system in Australia and the looming ecological challenges, radical changes to the current system are required. The central concepts of herbal practice, in particular vitalism and holism, lead to approaches to healthcare which are potentially both costeffective and ecologically sustainable. A robust and independent profession of western herbalists, with their philosophy articulated and restored, could provide a valuable and sustainable contribution to Australian healthcare.

This thesis is about the contemporary challenges facing herbal medicine. Specifically it concerns the difficulties faced by Australian herbalists in their attempts to maintain authority over the knowledge base of their craft and a connection with traditional understandings of the uses of plant medicines, while at the same time engaging with biomedicine and the broader Australian healthcare system. It contributes to the study of the nascent field of qualitative studies in contemporary western herbal medicine by making three main arguments.Firstly, Australian herbal medicine is characterised by its origins as a European colonial practice and its history of professional marginalisation during most of the 20th century. Secondly herbal practitioners have been unable to capitalise significantly on a surge of public popularity in the closing years of the 20th century which brought with it the interest of industry, the scrutiny of regulators and the renewed attention of biomedicine. Herbalists continue to struggle for recognition in the face of these more powerful interests. Thirdly it is argued that herbalists are attempting to gain legitimacy and acceptance as a healthcare profession through a process of underpinning their knowledge base with science, which is replacing their traditional philosophical basis. This has the effect of weakening the ability of herbalists to maintain their identity as an independent profession and makes its knowledge base vulnerable to appropriation by other healthcare professions.Gross’ model of the cultural location of traditions in contemporary societies is used to clarify the situation of herbalists and to identify problems consequent to the political choices they have made or which have been forced upon them. Gross suggests that traditions which place themselves close to power have difficulty in maintaining their own character and integrity, but that other cultural locations are also problematic and limit full participation in society. vi It is argued that there are compelling reasons to move beyond Gross’ analysis and to find ways to strengthen the independence of the herbal profession. Given the financial problems facing the current healthcare system in Australia and the looming ecological challenges, radical changes to the current system are required. The central concepts of herbal practice, in particular vitalism and holism, lead to approaches to healthcare which are potentially both costeffective and ecologically sustainable. A robust and independent profession of western herbalists, with their philosophy articulated and restored, could provide a valuable and sustainable contribution to Australian healthcare.

This research investigated the transformative and extraordinary experiences of nurse healers. The broad aim of the research was to promote the role of the healer in nursing by providing data on the experiences specific to nurse healers’ evolution as healers. The research was theoretically informed by van Manen (1990, 1984) and utilised hermeneutic phenomenology. Van Manen’s emphasis on writing as the key element of phenomenology in lived experience research was employed to bring forth a sense of lived immediacy and aesthetic colour essential to phenomenological understanding. The thesis was also theoretically aligned with the conceptual model of nursing as a caring-healing profession, developed by Jean Watson (1999, 1990a, 1988, 1985a). In particular, this research drew on Watson’s explicit connection of nursing with healing and nursing practice with transformational, transpersonal and esoteric insights. There were eleven nurse (nine women and two men) participants in the study. All participants identified strongly as healers. Selection was based on how long, and important to the individual was their commitment to being a healer. The data collection method used was semi structured interview with a predominant focus on storytelling. The overarching theme of ‘Walking Two Worlds’ was identified, and within that five essential themes were uncovered: (1) Belonging & Connecting; (2) Opening to Spirit; (3) Summoning; (4) Wounding & Healing Journey; and (5) Living as a Healer. Implications for nursing discussed include the need for the profession to provide support to nurse healers as they encounter challenging experiences and to allow for ontological flexibility regarding the esoteric aspects of human/spiritual experience revealed by this research. Further the need to extend the understanding invoked by healing beyond the obvious and opening vistas into experience which have been previously repudiated by domineering, narrow and spirit-denying powers in our society is also discussed.

Abstract THE CHARACTERIZATION OF CHIMERIC CHAPERONE FLAGRP170 AS A NOVEL RADIOPROTECTANT By Tyler Nguyen, M.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2017 Major Director: Dr. Xiang-Yang (Shawn) Wang, Ph.D., Professor, Department of Human and Molecular Genetics Radiation therapy (RT) is restricted by toxic effects on adjacent normal tissue, which limits RT efficacy in cancer treatment. Damage to normal tissue, such as radiosensitive intestine and bone marrow compartments, results in acute radiation damage. To reduce normal tissue injury in the setting of RT, we examine the potential radioprotectant, Flagrp170, a chimeric protein. Flagrp170 is comprised of glucose-regulated protein-170 (Grp170) and a NF-κB activating sequence derived from flagellin. We show that Flagrp170 can protect normal tissues post irradiation, indicated by TUNEL and clonogenic assays. However, treatment with Flagrp170 does not influence tumor response to RT. Studies indicate that Flagrp170 activates the transcription factor NF-κB, a strong pro-survival signal. In addition, Flagrp170 can induce production of radioprotective cytokines as well. Data suggests that Flagrp170 has potential as a novel radioprotectant in the setting of RT. The combination of Flagrp170 therapy and RT may lead to improved treatment outcomes.

Multifunctional agents for the management of highly heterogeneous diseases, like cancer, are gaining increased interest with the intent of improving the diagnostics and therapy of cancer patients. These agents are also important because more than one treatment modality is typically used for cancer therapy in the clinic. Further, nanotechnology offers a platform where more than one agent can be combined to help provide improved cancer diagnosis and therapy. Near-infrared light-activatable phototherapeutic agents have great potential in vivo. Body tissues have minimum absorption in the near- infrared range. They also have been shown to enhance the cytotoxic effect of chemotherapeutic drugs when used in combination with them. We have, hence, investigated the potential of two multifunctional targeted nanoparticles for combined chemo-phototherapy (employing near- infrared light activable agent) and for understanding their underlying cellular responses. The first is employing polymeric Poly-lactic acid-co-glycolic acid (PLGA) nanoparticles with simultaneous incorporation of Indocyanine Green (ICG) (a near-infrared light-activatable photothermal agent) and Doxorubicin (DOX) and surface conjugated with anti-Human Epithelial Receptor-2 (HER-2). The PLGA nanoparticles were subjected to two modes of hyperthermia, incubator and laser hyperthermia, to mimic whole-body and localized hyperthermia used clinically. These nanoparticles upon laser exposure showed a rapid heat shock protein 70 (HSP70) response in comparison to the cellular HSP70 response upon incubator hyperthermia exposure. However, 12h post-treatment, downregulation of HSP70, was observed, thus, causing cellular apoptosis or necrosis based on the degree of thermal insult. These targeted nanoparticles, simultaneously incorporating agents, suffer from the limitation of release of both the agents from the nanoparticles and the need to control their release for bringing in effective therapy. Therefore, the second multifunctional nanoparticle employing silver nanoparticles (AgNPs) conjugated with Doxorubicin was formulated. AgNP serve as a near-infrared activatable agent itself, other than serving as a drug delivery vehicle. Thus, these nanoparticles only require the need to control the release of DOX alone. We further studied their mechanism of action, which included enhanced reactive oxygen species (ROS) production and reduction of intracellular thiol levels.