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.

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Individuals are becoming more dependent on medication for conditions such as chronic-pain, anxiety, and depression. It is reported that patients are often overprescribed medication while health outcomes do not improve. The medicalization of society is distracting attention from the possibility of other therapies such as complementary or alternative medicine (CAMs) that can improve health outcomes if they were as supported as pharmacological research and better received by the medical community. Yoga and meditation, the components of Mindfulness Based Stress Reduction (MBSR) and yoga therapy, have been shown as effective CAMs for cases of anxiety and depression related to chronic illness or chronic pain. There is little agreement in research, among yoga practitioners, and in the medical community on how to prescribe the delivery of yoga therapy interventions to reduce pain, depression, or anxiety. The purpose of this quantitative study and, to address this gap in the literature, is to provide the medical community protocols for the delivery of yoga therapy and to discover a “dose response” for yoga therapy among 6 individuals suffering pain and related affective disorders such as anxiety and depression. The findings of this study showed no significant difference among individuals who practice yoga therapy at the rate of one or three times per week on reported levels of depression, anxiety, pain, perceived stress or quality of life depending on the rate of practice. This study could impact the over-prescription of medication and reduce the dependence on psychopharmacology for management of affective disorders

Bakgrund: Fantomsmärtan är vanlig hos patienter som amputerat en kroppsdel. Att behandla smärtan är en utmaning för sjuksköterskan där en kunskap om fenomenets manifestation och de komplementärmedicinska alternativ som finns att tillgå är viktiga redskap för att stötta patienten genom hela vårdförloppet. Syfte: Syftet var att belysa sjuksköterskans roll i omvårdnaden av patienter med fantomsmärta som behandlas med komplementärmedicinska behandlingar. Metod: Studien var en litteraturstudie med induktiv ansats baserad på kvalitativ och kvantitativ forskning med olika design. Resultat: Litteraturstudiens resultat presenteras i två kategorier: Sjuksköterskans roll före amputationen och Sjuksköterskans roll efter amputationen. Sjuksköterskan har en viktig roll i behandlingen av fantomsmärta där den personcentrerade vården är i fokus. Kunskap om fantomsmärtans manifestation samt komplementärmedicinska alternativ, till exempel spegelterapi och VR med AG, är nödvändig för att bygga förtroende och finna rätt behandlingsalternativ till den unika patienten. Konklusion: Sjuksköterskans förståelse för patienter med fantomsmärta samt patientens hälsolitteracitet har en central roll i omvårdnaden. Tidigt implementerande av en vårdplan, utbildning om fantomsmärtans karaktär samt information om komplementärmedicinska behandlingsalternativ skapar förtroende mellan sjuksköterska och patient. Ytterligare forskning kring fantomsmärtan och de komplementärmedicinska metoderna är nödvändig för att arbeta fram tydligare riktlinjer och en bredare förståelse för fantomsmärtan. / Background: Phantom limb pain is common in patients who have amputated a body part. Treating the pain is a challenge for the nurse where a knowledge of the phenomenon's manifestation and the complementary medicine alternatives that are available are important tools for supporting the patient throughout the care process. Aim: The aim was to illustrate the nurse’s role in the care of patients with phantom limb pain who are treated with complementary medicine methods. Method: The study was a literature study with an inductive approach based on qualitative and quantitative research with different designs. Results: The results of the literature study are presented in two categories: Nurse’s role before the amputation and Nurse’s role after the amputation. The nurse has an important role in the treatment of phantom limb pain where the person-centered care is in focus. Knowledge of the manifestation of phantom limb pain as well as complementary medicine alternatives, such as mirror therapy and VR with AG, is necessary to build trust and find the right treatment alternative for the unique patient. Conclusion: The nurse's understanding of patients with phantom limb pain and the patient's health literacy has a central role in nursing. Early implementation of a care plan, education about the nature of phantom limb pain and information about complementary medicine treatment options creates trust between nurse and patient. Further research on phantom limb pain and the complementary medicine methods is necessary to work out clearer guidelines and a wider understanding of phantom limb pain.

Individuals with epilepsy manage the clinical manifestations of the condition, primarily seizure-related activity, with daily use of pharmacologic agents, making it one of the most common neurological conditions treated with drug therapy for symptom management. Pharmacologic agents for epilepsy, also known as anti-epileptic drugs (AEDs), are commonly prescribed to treat seizures and neurologic conditions associated with epilepsy but can lead to a reduced quality of life and many unwanted side effects. Complementary and alternative treatments can also provide relief from seizures associated with epilepsy. The purpose of this literature review was to evaluate the effectiveness of complementary and alternative treatments compared to pharmacological treatment for individuals with epilepsy. A literature review examining different alternative treatments, such as physical activity, medical cannabis, neurostimulation, and various diets, and their benefits on seizure reduction, seizure frequency, and the quality of life was conducted from various online databases. Research articles published from 2003 to 2020 that focused on the benefits of complementary and alternative therapies in controlling the clinical manifestations of epilepsy were included for synthesis. Results from 10 studies that used a complementary or alternative therapy as a treatment for epilepsy, alone or in combination with pharmacological therapy, were compared for effectiveness on clinical manifestations. Seventy percent of the studies analyzed show at least a fifty percent reduction in seizure frequency. The studies suggest that complementary and alternative therapies can be effective as monotherapy or as adjuvant agents for reducing seizure frequency, reducing seizure duration, and improving quality of life. Although benefits were found in each study, many studies were performed on animals or had small sample sizes, indicating the need for further research.

In people with Multiple Sclerosis (MS) balance impairments may lead to increased falls and mobility loss. In quiet stance, people with MS display greater postural sway than healthy controls. Tai Chi is a Chinese martial art that has decreased the risk of falling in frail elderly individuals (Wolf et al., 1996). The purpose of this study was to determine if a three week Tai Chi intervention would improve postural stability in people with MS. Seven participants (6F/1M, age 48.5 ± 10.8 years, height 1.66 ± 0.08m, mass 68.6 ± 19.8kg) attended nine one hour training sessions to practice two types of Tai Chi: standing meditation and slow walking. Postural stability was assessed before and after training using average center of pressure (CoP) velocity, total excursion and time to contact (TtC) for the static trials, and dual and single limb support times for the walking trials. To measure postural stability trials of quiet stance (QS), Tai Chi standing meditation with (SMA) and without arms (SM), tandem stance (TS), preferred speed walking (PW) and slow speed walking (SW) were assessed. Kinematic data recorded by a 12 camera motion capture system (Qualysis AB), and kinetic data collected from a single forceplate (AMTI) were used to compute net CoP. Because functional parameters can influence stability, strength obtained from a chair rise test and neural drive obtained from a foot tapping test were obtained. All results were assessed with paired t-tests (p.05). For SMA, average CoP velocity (p=.006) and excursions (p=.023) increased, and average TtC (p=.020) was reduced. For TS average CoP velocity (p=.06) and excursions (p=.09) trended towards decreased values, and average TtC (p=.045) increased. With the exception of increased left single limb support time (p=.009) PW and SW were not affected by the intervention. In conclusion, the increased neural drive, muscular strength, and postural stability in TS supports the idea that a three week Tai Chi intervention is effective at improving static balance in people with MS.

Obesity is an urgent global public health concern as prevalence rates continue to increase, especially among children. At the cellular level obesity is defined by an increase in adipocyte number (hyperplasia) and size (hypertrophy). Both lead to the dysfunction of adipose tissue, which has been identified as the link between obesity and chronic disease. Bioactive compounds, naturally occurring in fruits and vegetables, hold enormous potential in regulating adipocyte biology. Quercetin, the most commonly consumed dietary flavonoid, is a strong potential anti-obesity agent that has been implicated as an AMP-activated protein kinase (AMPK) activator and shown to ameliorate symptoms of metabolic syndrome in vivo. Here we investigated quercetin’s effect on (1) adipogenesis, the process of increasing adipocyte number, and (2) metabolism of mature adipocytes. In 3T3-L1 preadipocytes, quercetin dose-dependently inhibited adipogenesis, as evidenced by decreased lipid accumulation and expression of adipogenic markers such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/ enhancer binding protein (C/EBP) α, adipocyte fatty acid binding protein 2 (aP2), and acetyl-CoA carboxylase (ACC) on mRNA and protein levels. This inhibitory effect was limited to the early stages of adipogenesis (0-36 hours), and quercetin treatment altered the normal expression pattern of cell cycle related genes Cyclin A and p27, indicating quercetin may inhibit adipogenesis through cell cycle events. We next investigated quercetin’s ability to activate AMPK and the metabolic pathways related to AMPK activation: lipolysis and b-oxidation. Quercetin increased phosphorylation of AMPK and its downstream target ACC. Further, quercetin treatment (100μM) increased free fatty acid content in the media through an AMPK-dependent mechanism. Quercetin up-regulated mRNA expression of uncoupling proteins 3 (UCP3) and peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1a), indicating that quercetin may induce mitochondrial oxidative pathways, also through an AMPK-dependent pathway. These findings suggest (1) quercetin inhibits adipogenesis through the regulation of early cell cycle events required for adipogenic differentiation, and (2) quercetin’s activation of AMPK induces lipolytic and oxidative pathways. Taken together, quercetin could be further developed as an anti-obesity agent because of its potential to inhibit both hyperplasia and hypertrophy in vitro.

For the past 40 years, antiangiogenic approaches have been of major interest in the development of methods to cure and prevent cancer. Angiogenesis, the development of blood vessels from pre-existing vascularization, is essential for cancer growth and spread of metastasis through the delivery of nutrients and oxygen essential to sustain the metabolic activity of these malignant cells. Blocking access to blood will cause cancerous cells to assume a dormant state creating inactive micro-tumors innocuous to the host. Angiostatin, the internal fragment of the fibrinolytic zymogen plasminogen, has shown great potential in reducing cancer size and number of metastatic colonies in animal models. Owing to the success of these preliminary results angiostatin is currently on clinical trials. Plasminogen is known to be transferred from blood to milk during lactation. The objectives of this research were to: 1) investigate the ability of various proteases in cleaving plasminogen, both from human and bovine sources, and consequently release the angiostatin like fragment; 2) determine the anticancer activity of bovine angiostatin; 3) examine ability of the antiangiogenic fragment to survive digestion; 4) purify the fragment of interest through column chromatography. Production of angiostatin was tested through hydrolysis of plasminogen via Bacillus Polymyxa protease (or dispase I), elastase, lactic acid bacteria and Bacilli originated enzymes. Once proteases capable of angiostatin like peptide production were identified, and sequence analysis of the fragments obtained conducted to confirm that bovine angiostatin was indeed produced, ability of angiostatin, both human and bovine, in inhibiting malignant melanoma as well as colon cancer cells was evaluated in vitro. From the results obtained we can confirm that bovine angiostatin inhibitory activity on cancerous cells is similar to that observed for human angiostatin. Analysis of bovine angiostatin survival through in vitro human digestion model was also examined. Results show good possibility of angiostatin surviving digestion, even if confirmation of these results is required through further in vivo studies. Additionally, digestive enzymes such as trypsin and α-chymotrypsin showed ability in cleaving plasminogen directly to release a 25kDa fragment. Knowing that each kringle has some degree of anticancer activity it would be of interest to further study the possibility of angiostatin related fragments to be produced during milk digestion. Finally, affinity chromatography through L-lysine used to purify human angiostatin resulted to be an adequate method for bovine angiostatin purification. Preliminary results obtained from this study open a new area worth investigating to uncover the potential of using bovine angiostatin in the development of novel food products capable of cancer prevention.