This study examined quantitative EEGs of six individuals with chronic pain and compared them to an age- and gender-matched normative database of healthy control subjects in an attempt to discern whether a particular pattern of resting state EEG activity is associated with chronic pain. In the chronic pain group, significantly reduced absolute power was seen in delta and theta bandwidths at frontal sites in the eyes-closed condition. In the eyes-open condition, significantly reduced absolute power was seen in delta, theta, and alpha bandwidths at frontal, central, and temporal sites, and increased relative high beta power was seen in the parietal region. Reduced theta/high beta and delta/high beta ratios were seen in the parietal region. Quantitative EEG neuromarkers of chronic pain are suggested.

Magister Scientiae Dentium - MSc(Dent) / There are both physical and emotional components which are associated with the chronic pain of TMD patients. One of the difficuhies in making an accurate assessment of each component, is the lack of objective criteria for quantitative measurement of the emotional component. This need, lead to the development of Research Diagnostic Criteria (RDC) by Dworkin and LeResche (1992). The aim of this study was to use RDC criteria to record the prevalence, and associations between Axis I (physical) and AXIS TI(emotional) factors in a sample of 100 patients attending a TMD Clinic. Patients were examined using the RDC guidelines and the diagnosis classified as either, myogenic, disc displacement or arthritis. Patients completed a self-administered personal history questiotmaire which analyzed emotional factors including, chronic graded pain, depression and nonspecific physical symptoms such as headaches, faintness and lower back pain.

Depression is an extremely common, devastating psychiatric syndrome with profound effects on the structure of neurons and the proteins that they express. However, the pathophysiology of depression remains unclear despite decades of extensive research efforts, and this lack of understanding makes it difficult to develop effective treatments. It is extremely problematic that conventional antidepressant drugs do not work for many patients, and those that do respond require weeks to months of continuous treatment before adequate therapeutic improvement is achieved. Therefore, there is a clear unmet need to develop mechanistically novel antidepressant compounds that are well-tolerated, more effective, and faster acting. Subjecting rats to repeated-corticosterone (CORT; stress hormone analogous to cortisol for humans) injections produces a depressive-like phenotype that can be used to make inferences about the human condition and screen compounds for antidepressant properties. Our laboratory has previously found that stress downregulates hippocampal reelin in a similar manner to that seen in depression patients, and that drugs with antidepressant actions recover this deficit. This provided a rationale to administer reelin directly into the hippocampus, which rescued behavioral and neurochemical deficits, but intrahippocampal infusions are not clinically viable. Reelin is expressed in the periphery and blood as well as the brain, so the aims of the collection of studies described here are to evaluate the antidepressant-like properties of peripheral intravenous (i.v.) reelin. In the first experiment, the antidepressant-like effects of several dosages of reelin (3/5μg given every 5/10 days) were evaluated in rats that were exposed to 3-weeks of daily CORT (40mg/kg) injections. I found that all the dosages of reelin attenuated CORT-induced despair-like behavior in the forced-swim test (FST) and normalized alterations in serotonin (5-HT) transporter (SERT) membrane protein clustering (MPC) in blood lymphocytes. Reelin treatment also increased reelin-immunoreactive (IR) cell counts in the hippocampal dentate gyrus (DG) subgranular zone (SGZ), but it had less of an effect on neurogenesis as measured by the number and maturation rate of doublecortin (DCX)-IR cells. Interestingly, the lowest dosage used also rescued the number of reelin-IR cells in the hypothalamic paraventricular nucleus (PVN). This suggested that the restoration of SGZ-reelin plays a pivotal role in attenuating depressive-like behavior and that 3μg every 10 days was the most effective dosage that was tested. Using the lowest dosage that showed to be effective in the first experiment, I then evaluated if male and female rats responded similarly to i.v. reelin using a larger battery of behavioral tests. Post-mortem tissue analyses focused on reelin and receptors that bind gamma-aminobutyric acid (GABA) and glutamate in the SGZ, which have been implicated in psychiatric disorders and the mediation of fast-acting antidepressant responses. I found that reelin rescued the FST- behavioral and neurochemical alterations induced by CORT similarly in both sexes, indicating that it may have therapeutic effects by normalizing inhibitory/excitatory transmission. I also evaluated the effect of i.v. reelin on neurogenesis in females and found that, akin to males, the regulation of adult-born cells by peripheral reelin is unlikely to mediate the antidepressant-like effects. The goal of the third experiment was to examine whether the antidepressant-like effects of peripheral reelin are achieved in a rapid manner. I found that a single 3μg injection after 3 weeks of CORT significantly decreased behavioral deficits in the FST 24 hours later in both sexes. Reelin also partially rescued cognitive deficits and expression levels of reelin, GluN2B, and mitochondrial-related pro-apoptotic factors bcl-2 associated X protein (BAX) and cytochrome C (CytC) in the DG. In addition, a single injection of reelin fully recovered the number of GluA1-expressing cells and partially recovered SERT cluster size in males, whereas reelin partially recovered GluA1-IR cell counts and fully recovered SERT cluster sizes in females. Reelin had modest effects on DCX-IR cells in both sexes. The final chapter summarizes and discusses my findings, which suggest that the antidepressant-like effects of peripheral reelin are associated with the recovery of neurochemical deficits that strengthen neurotransmission, at least in the hippocampus. Therefore, developing reelin-based therapeutics with antidepressant activity would be a fruitful area of research, although additional mechanistic, pharmacokinetic, and pharmacodynamic studies are essential. / Graduate

Neuropathic pain is a common problem in clinical practice, affecting patients physically, emotionally, financially, and socially. Current treatment includes antidepressants, antiepileptics, and opioid analgesics. Bupropion is a specific inhibitor of neuronal noradrenaline reuptake and a weak inhibitor of dopamine reuptake, which shows some promise in the treatment of neuropathic pain.

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathway is constitutively active in a variety of cancers, including chronic lymphocytic leukaemia (CLL). The importance of this signalling pathway identifies it as a prime therapeutic target; however, the complexity and potential side effects of inhibiting NF-κB have thus far made the clinical use of NF-κB inhibitors a relatively unexplored resource in this disease. This article discusses the role of NF-κB in CLL as a common crossroad for pathways promoting drug resistance in CLL. We provide the background on how this pathway contributes to both spontaneous and drug-induced apoptosis. Potential new avenues to regulate this pathway in CLL are also discussed.

Post-traumatic stress disorder (PTSD) is characterized by fear extinction deficit; chronic stress worsens this deficit. Using a Chronic Unpredictable Stress (CUS) model, we previously found that CUS increased fear extinction deficit in female mice and knockout of Ciliary Neurotrophic Factor (CNTF) attenuated it. The amygdala, specifically the medial amygdala, is strongly associated with fear conditioning and extinction. CUS increased CNTF and reduced Urocortin 3 (UCN3) in the medial amygdala, suggesting CNTF-mediated UCN3 inhibition may be involved in CUS-induced deficit of fear extinction. The medial amygdala connects to the hypothalamic paraventricular nucleus (PVN) via posterior bed nucleus of stria terminalis (pBNST) and mediates the stress response (Fig. 1). The objective of this project is to determine whether CUS affects CNTF, UCN3, and CNTF-related cytokine leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) in the pBNST and hypothalamic PVN. Hippocampal CNTF expression was also examined as a brain region outside of the medial amygdala-pBNST-hypothalamic PVN circuitry. 4 groups (5 mice/group) of CNTF+/+ and CNTF-/- mice were treated with 4 weeks of CUS or control handling. At the end, fresh brain samples were collected. The hypothalamic PVN, pBNST and hippocampus were punched out from 600-700 um cryostat frozen sections. CUS was applied for 4 weeks. The control mice were handled daily for 4 weeks. RNA was extracted from tissue using QIANGEN Rneasy mini kit. BCA assay was performed to analyze protein concentration, then 10% SDS gel was used to run the protein samples. Statistical analysis included one-way ANOVA followed by Bonferroni multiple comparison or 2-tailed T test. p <0.05 was defined as significant difference. In the pBNST, CUS did not affect CNTF and UCN3 mRNA expression. However, UCN3 protein was upregulated by CUS in CNTF+/+ but not CNTF-/- mice, suggesting CNTF inhibits UCN3 expression, possibly through post-transcriptional mechanism. CUS did not alter LIF and IL-3 in the pBNST. CUS did not alter CNTF mRNA expression in the PVN and further study will measure UCN3 mRNA and protein in the PVN. Finally, there was no CUS effect on CNTF, LIF and IL-6 mRNA in the hippocampus. These results and further studies are useful in development of therapeutic medications and drug targets in the case of chronic stress.

Nutrition education programs in the prevention of chronic diseases has flourished over the last 15 years. Investigators continue to demonstrate that soy consumption plays a role in decreasing chronic diseases such as cardiovascular disease, cancer, osteoporosis and problems regarding menopause. Although research focuses on soy benefits regarding chronic disease, to date, no program exists focusing on soy consumption.164 surveys distributed to 18-65 year-olds in Southwest Virginia assessed the population's chronic disease knowledge and information sources regarding soy foods and three nutrition education programs. Purchases of and opinions on soy products along with 62 single-blind taste evaluations comparing soy and non-soy taste preferences were assessed. 73.4% of the population sample knew at least one of three nutrition programs while 37.1% knew soy's relationship to chronic disease. Information sources for both were significantly (p<.006) higher for magazines and newspapers. Health and belief of not liking the taste of soy were significant (p<.017) reasons influencing purchase of soy foods. Tofu and soy burgers were consumed significantly (p<.001) more than other soy foods. No significant (p>.05) difference in preference was found between all cookies and muffins. Women knew significantly (p<.04) more about soy than men. Knowledge about soy was significantly (p<.03) correlated with soy consumption.Results indicate a need for soy education and consumption in preventing chronic diseases. Target populations should focus on non-Asians, males, 18-24 years, with less than a college education level. Implementing a soy education program in preventing chronic diseases is feasible, necessary, and cost-effective. / Master of Science

A collection of poems around themes of motherhood, chronic illness, memory, and internal and external landscapes coalescing.

Philosophiae Doctor - PhD / This study set out to develop an integrated model that could explain the sustainable adoption of mHealth, among the rural populations. With a penetration level of 130%, the ubiquitous mobile phone infrastructure was conducive to implementing mHealth even in the remote and rural regions of Kenya, which otherwise grapple with inequality and inequity of the healthcare system and a rising chronic diseases burden. Whereas mHealth could provide a suitable low-cost solution to disseminate targeted education to the grass-root masses in a short time, its uptake was reported to be low and short- lived. Therefore, the purpose of the study was to evaluate the factors that could explain the low levels of mHealth adoption for education on chronic diseases in the rural settings of the country. From a theoretical perspective, a combination of four social behaviour change theories, three technology adoption models, and two health behaviour change models guided the development of the theoretical framework. Seven factors were subsequently tested: perceived susceptibility, perceived severity, perceived usefulness, perceived ease of use, social influence, age, and language literacy, all of which measured mobile phone use for health literacy. Thirteen hypotheses were formulated from these factors.

Indiana University-Purdue University Indianapolis (IUPUI) / This research explores the illness experiences of women and men who received a Celiac Disease Diagnosis as an adult in addition to the impact it had on their social interactions and every-day lives. Investigation of illness experiences were conducted through the use of semi-structured interviews which explored diagnosis experiences, gendered experiences, and life style impact. Significant findings of this research indicated that there are gendered diagnosis experiences among women and men who are diagnosed with this disease. More specifically, female participants reported diagnosis experiences similar to that of a contested illness. In contrast, male participants reported diagnosis experiences that reflect a routinely defined illness. Despite these results, additional research is necessary in order to better understand gendered experiences among those who are diagnosed with Celiac Disease as an adult.