Impact of Psychological Factors on Adolescents with Anterior Knee Pain

Problem and purpose: Psychological factors impact self-report measures of pain and function among adults with anteriorknee pain (AKP), but we do not know (1) if psychological factors also impact pain, self-reported function, and objective measures of function among adolescents with AKP and (2) if a psychological intervention would affect function. The purpose of this dissertation is to determine the impact of psychological factors on pain, self-reported function, and objective measures of function in adolescents with AKP. Methods: This dissertation was prospective, with three separate studies. Two were cross-sectional observational studies, and the third was a randomized-controlled trial. Patient questionnaires were used to describe psychological beliefs, including fear avoidance (fear avoidance beliefs questionnaire-physical activity), kinesiophobia (Tampa scale for kinesiophobia-11), and paincatastrophizing (pain catastrophizing scale-child) in adolescents with AKP aged 12-17 years. In research study #1, self-reported function, pain, and clinical measures of function were assessed. In research study #2, three-dimensional motion analysis was used to assess movement patterns during a single leg hop for distance in a subset of the participants (n=30). In research study #3, participants were randomly assigned to a psychologically-informed education group or a control group. Change in self-reported function was assessed over six weeks. Results: Adolescents with AKP (n=87, 62% female, age 14.6 ±1.7 years) and healthy controls (research study #2 only, n=10, 60% female, age 15.5 ±1.8 years) were recruited for participation. Research study #1 identified a significant mild-moderate adverse association between psychological beliefs, self-reported function (r = -0.59), pain (r = 0.34), hip abductor strength (r = -0.41), and single leg hop distance (r = -0.38). Research study #2 found no significant between-group differences in movement patterns in adolescents with elevated or low maladaptive psychological beliefs. Research study #3 found that adolescents who received a brief psychologically-informed educational intervention had significantly greater short-term improvements in function compared to controls (mean difference of 8.0 points, 95% CI 2.4, 13.5; p = 0.01). Conclusion: Maladaptive psychological beliefs were adversely associated with self-reported function, pain, and certain aspects of objective function. Providing a brief psychologically-informed intervention significantly improved maladaptive beliefs and self-reported function among adolescents with AKP

The Neuroprotective Role Of Vitamin D On Neurons In A Central Nervous System Autoimmune Disease

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). Childhood vitamin D insufficiency is a known risk factor of MS. However, it remains unclear how vitamin D levels before adolescence affect the susceptibility to disease. We hypothesize that vitamin D increases IL-34 production, which directs microglia into an anti-inflammatory phenotype, preventing neurodegeneration in a developing CNS. We observed an increased expression of IL-34 mRNA in primary neurons and neurons derived from a mouse Neuroblastoma (N2a) cell line after treating with calcitriol, the biologically active form of vitamin D. Additionally, immortalized murine microglia (BV-2) and primary microglia treated with IL-34 showed a decrease in pro-inflammatory cytokines and an increase in anti-inflammatory molecules compared to untreated controls upon lipopolysaccharide (LPS) stimulation. These findings indicate that microglia can be directed to an anti-inflammatory phenotype by IL-34, which is produced by vitamin D-treated neurons. To study how vitamin D signaling in childhood influences the risk of developing disease in vivo, we generated a transgenic mouse model using single-neuron labeling with inducible Cre-mediated knockout (SLICK) mice. This allows manipulation of VDR levels on neurons during different ages of life. We found that SLICK f/+ mice have decreased VDR expression when evaluated by immunohistochemistry. These mice showed that low levels of vitamin D during development caused increased disease severity through inducing experimental autoimmune encephalomyelitis (EAE). By understanding the mechanism by which vitamin D levels influence multiple sclerosis susceptibility, vitamin supplements could be administered to prevent high risk populations from developing this incurable disease.No embargoAcademic Major: Biomedical Scienc

MODIFICATION OF 2D MATERIALS UTILIZING FUNCTIONAL POLYMER INTERFACIAL LAYERS

This dissertation describes the modification of 2D transition metal dichalcogenides (TMDCs). These materials exhibit unique electronic properties, ranging from metallic to insulating, and can transport either electrons (n-type) or holes (p-type). Polymers containing electronically-active moieties offer a path to control the electronic properties of a 2D material without altering the inherent structure of the semiconductor. This dissertation focuses on the synthesis of polymers bearing chalcogen-rich or zwitterionic moieties to alter the electronic and solution properties of 2D materials. Chapter 2 describes polymers containing sulfur-rich tetrathiafulvalene (TTF) and their effects as electroactive coatings on the TMDC molybdenum disulfide (MoS2). These polymers were anticipated to not only promote adhesion to MoS2 through sulfur-sulfur interactions but also modify the work function of the semiconductor through the donation of electrons at the semiconductor/polymer interface. TTF polymers were synthesized by ring-opening metathesis copolymerization (ROMP) and reversible addition fragmentation chain transfer (RAFT) polymerization. TTF polymers stabilize suspensions of chemically exfoliated MoS2 nanosheets, contrary to a pyrene-substituted polymer of similar structure, demonstrating the importance of a sulfur-rich structure for interaction with MoS2. Kelvin probe force microscopy (KPFM) was used to examine the shift in work function after a thin polymer layer was applied to MoS2 which revealed a decrease in work function by 0.24 eV, expected for n-doping. Chapter 3 examines the complementary case to TTF—doping with a sulfur rich electron acceptor bithiazolidinylidene (BT). Functional BT monomers were synthesized by the reaction of a primary amine with carbon disulfide and dimethylacetylene dicarboxylate. BT-containing polymers were then accessed by condensation of a BT-diol with hexamethylene diisocyanate to form polyurethanes. The polymers exhibited thermal stability and solubility in an array of solvents and, upon coating single layer MoS2 grown by chemical vapor deposition (CVD), the SPC decreased by 0.16 V, signifying an increase work function and confirming p-doping. Chapter 4 progresses the previous two chapters through the analysis of the underlying substrate and its role in the efficacy of doping MoS2 with small molecules TTF and BT. CVD grown MoS2 on silicon oxide (SiO2) and aluminum oxide (Al2O3, sapphire) were coated with thin layers of TTF and BT and the change in work function was monitored by KPFM. MoS2 on Al2O3 showed a work function decrease of 1.24 eV when coated with TTF, displaying a remarkable increase in the efficacy of n-doping compared to using SiO2 as the underlying dielectric. Similarly, when coated with BT, MoS2 with Al2O3 as the dielectric displayed a 0.8 eV increase in the work function representing a four-fold increase in the magnitude of work function shift when compared to using SiO2 as the underlying substrate. We rationalize this increase in the efficacy of doping MoS2 by an increase in the static polarizability of the substrate when using Al2O3 causing a decrease in the effective measured dipole screening being probed at the dopant/semiconductor interface. Chapter 5 concludes with the development of zwitterionic photoresists used to simultaneously pattern and dope 2D materials. We developed a novel photoresist composed of zwitterionic poly(sulfobetaine methacrylate) (PSBMA) copolymers with methyl methacrylate and implemented these photoresist in the fabrication of graphene transistors. Multiple copolymers were synthesized by conventional free-radical polymerization in trifluoroethanol with feed ratio matching experimental incorporations. These zwitterionic photoresists displayed resolutions approaching 100 nm, matching conventional methacrylic photoresists. Transistors were fabricated on CVD-grown single layer graphene deposited on p-type Si/SiO2 and the polymer was used to pattern over the device to afford multiple, unique devices on a single graphene flake. Polymer covered devices showed n-doping indicated by a shift in the charge neutrality point in the current-voltage curves. Furthermore, a single device with polymer covering half of the device exhibited p-n junction characteristics (high on currents at high gate biases) demonstrating the ease of fabrication of these devices using this class of polymer photoresists

Acute Bilateral Ophthalmoplegias

Bilateral ophthalmoplegia is that condition of weakness or paralysis involving one or more ocular muscles in each eye. Its sudden appearance due to an acute ocular myopathy is indeed unusual. Swash reported a single patient with acute necrotizing orbital myositis and carcinomatosis neuromyopathy. The more common bilateral ocular muscle diseases, such as dysthyroid exophthalmopathy, orbital myositis, and progressive external ophthalmoplegia, develop insidiously and are restricted to the orbit

Uncommon Disorders of the Lower Spinal Region A Report on Eleven Patients

Prompt diagnosis of lower spinal diseases is essential for successful treatment. Appropriate medical therapy or surgical decompression arrests progression and reverses existing neurologic deficit. Delayed or improper diagnosis seriously jeopardizes the patient’s ultimate neurologic status. Too often early symptoms are disregarded or passed over as insignificant