Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the United States (Kowal, Dall, Chakrabarti, Storm, & Jain, 2013), affecting approximately 1 million Americans (American Parkinson’s Disease Association, 2020). However, there is limited research on the employment experiences of individuals with Parkinson’s disease (PD) (Koerts, Konig, Tucha, & Tucha, 2016). Informed by the capability approach (Sen, 2009) and social cognitive career theory (Lent & Hackett, 1994), this dissertation study addressed gaps in the extant literature, examining what employment options individuals with Parkinson's disease perceive as feasible after disease onset. This research explored the effects of contextual factors on employment options, including how understanding of workplace accommodations influences employment options, the role of discrimination and stigma in shaping employment options, and the extent to which individuals with Parkinson’s disease are receiving work-related decision support from health care providers. The author conducted individual semi-structured interviews with 23 adults under the age of 65 with Parkinson’s disease. Interviews were audio-recorded and transcribed. The author utilized an integrated approach to analysis, primarily employing a thematic analysis approach, as outlined by Braun and Clarke (2006). Additionally, a more interpretive analysis strategy (the Listening Guide, as outlined by Gilligan, Spencer, Weinberg & Bertsch, 2003) was integrated into the broader thematic analysis in order to deepen analysis of discrimination and stigma. Findings highlight specific facilitators and barriers to sustaining employment after the onset of PD, exploring how individuals with PD identify and gain crucial access to accommodations. This research demonstrates how a participant’s history of access to workplace accommodations influences participants’ perceived employment options, as well as the perceived effects of work on health. Participants’ narratives demonstrate how stigma and discrimination affect employment experiences and outcomes, influencing participants’ outcome expectations regarding current and future employment options. Participants reported that work-related conversations with health care providers were limited, with the data offering several explanations as to why these conversations were limited in nature. This study provides meaningful insights into the employment experiences of adults with Parkinson’s disease, with potential relevance to the experiences of adults with chronic and/or progressive diseases more broadly. These findings have important implications for social work and health care practice and education, disability policy, early intervention strategies after the onset of PD and priorities for future research. / 2024-05-31T00:00:00Z

Schizophrenia (SCZ) is a debilitating mental illness that affects roughly 1% of the world's population. Current theories about the etiology of this disease highlight disruptions in dopamine (DA) and glutamine. However, a more recent theory, the 'synaptic hypothesis' proposes that the fundamental pathology of this illness involves disruptions in synaptic transmission. The synapsins are a family of neuron specific phosphoproteins that play an important role in neurotransmitter release, synapse formation and maintaining a reserve pool of synaptic vesicles. Previous research has suggested that synapsin II has a role in the etiology of SCZ. For example, synapsin II mRNA is significantly reduced in the medial prefrontal cortex (MPFC) of patients, and synapsin II knockout mice display a variety of behavioural abnormalities which mimic human SCZ. Considering that SCZ may result from changes in the synapse, we wanted to further elucidate the role of synapsin II by measuring protein expression in post-mortem PFC samples. Overall, our results revealed that synapsin IIa and IIb are not significantly different between patients and controls, however, we hypothesize that synapsin II expression has been normalized in patients due to antipsychotic drug (APD) use. In fact, we discovered that treatment with atypical APDs significantly increases synapsin II in the prefrontal cortex (PFC) of patients, which may underlie the beneficial effects of these drugs. Another objective of our work was to investigate the expression of various presynaptic proteins in post-mortem samples from patients with Parkinson's disease (PD) Parkinson's disease, like SCZ, is an illness which involves dysregulated dopaminergic transmission and synaptic dysfunction. Therefore, we hypothesized that synapsin II might also be disrupted in patients with PD. Our results demonstrated that synapsin IIa and IIb are significantly reduced in the substantia nigra (SN), but not the striatum (STR) or PFC of patients, when compared to controls. Further, no changes were observed in the other synapsins (I or III), or synaptophysin, which suggests that synapsin II dysregulation may be specific to disorders which involve disruptions in dopamine (DA). / Thesis / Master of Science (MS)

Flavonoids are polyphenolics compounds that constitute a major group of plant specialized metabolites, biosynthesized via the phenylpropanoid/polymalonate pathways. The resulting specialized metabolites can be due to decoration of flavonoid compounds with sugars, usually glucose, by the action of regiospecific UDP-glycosyltransferase (UGT) enzymes. In some cases, glycosylation can involve enzymatic attachment of other sugar moieties, such as glucuronic acid, galactose, rhamnose or arabinose. These modifications facilitate or impact the bioactivity, stability, solubility, bioavailability and taste of the resulting flavonoid metabolites. The present work shows the limitations of utilizing mammalian UDP-glucuronosyltransferases (UGATs) for flavonoid glucuronidation, and then proceeds to investigate plant UG(A)T candidates from the model legume Medicago truncatula for glucuronidating brain-targeted flavonoid metabolites that have shown potential in neurological protection. We identified and characterized several UG(A)T candidates from M. truncatula which efficiently glycosylate various flavonoids compounds with different/multiple regiospecificities. Biochemical characterization identified one enzyme, UGT84F9, that efficiently glucuronidates a range of flavonoid compounds in vitro. In addition, examination of the ugt84f9 gene knock-out mutation in M. truncatula indicates that UGT84F9 is the major UG(A)T enzyme that is necessary and sufficient for attaching glucuronic acid to flavonoid aglycones, particularly flavones, in this species. Finally, the identified UG(A)T candidates were analyzed via homology modeling and site-directed mutagenesis towards increasing the repertoire of UG(A)Ts applicable for synthesis of flavonoid glucuronides with potential human health benefits in neurological protection.

<p>Lysosomal storage diseases (LSDs) are devastating neurological disorders caused by mutations in lysosomal hydrolases that result in accumulations of hydrolase substrates. Tay-Sachs disease (TSD) is an LSD that specifically results in the accumulation of GM2 gangliosides causing the activation of inflammatory signaling pathways, and leading to microglial activation and apoptotic cell death. The detailed mechanisms through which cell death occurs have not been completely elucidated, however, excitotoxicity is thought to play a major role. Here, we investigated the role of hypoxia-inducible factor-1α (HIF- 1α) and its effector microRNA, miR-210, and the impact they have on the expression of important molecules involved in excitotoxicity, namely neuronal pentraxin 1 (NPTX1) and potassium channel KCNK2 (KCNK2). We discovered that TSD neuroglia are inefficient at stabilizing HIF-1α in hypoxic conditions. Furthermore, miR-210 expression is significantly higher in TSD neuroglia compared to normal neuroglia at baseline and during hypoxia. In addition, TSD neuroglia expressed <em>NPTX1</em>, <em>NPTX2 </em>and <em>KCNK2 </em>at higher levels, and neuronal pentraxin receptor at lower levels than normal neuroglia, implicating excitotoxicity in disease pathogenesis. We also confirmed that miR-210 binds to the 3’ UTR of <em>NPTX1 </em>to repress its expression in TSD neuroglia. The presence of reverse hypoxia response elements in the promoter of KCNK2 and the repression of <em>KCNK2 </em>expression by HIF-1α stabilization suggest that KCNK2 is directly regulated by HIF-1α. Moreover, the glucosylceramide synthase inhibitor, NBDNJ, which is used to reduce ganglioside synthesis, caused expression of <em>NPTX1 </em>to decrease but <em>KCNK2 </em>expression to increase, indicating this drug can modify multiple parameters of disease. This study identifies major gene expression changes between normal and TSD neuroglia that affect the excitability and therefore the viability of TSD cells. This information provides new insight into the mechanisms of neurodegeneration experienced by TSD neuroglia.</p> / Master of Science (MSc)

no / There are a wide variety of ways to objectively detect neurological signs, but these either require special hard-ware (such as wearable technology) or patient behaviour change (such as engagement with smartphone tasks) [2]. Neither constraint applies to the technology of computer vision, which is the processing of single or multiple camera images by computer to automatically derive useful information. The only equipment involved is ubiquitous: camera and computer.We report a computer vision-enhanced video sequence from a 68-year-old man, diagnosed with idiopathic Parkinson’s disease 2 years previously.

General movements (GMs) are the spontaneous gross motor movements involving the whole body. GMs progressively develop as an infant ages. Several recent research studies involving the qualitative assessment of the GMs in infants have validated that GMs, or the lack of, are an accurate way diagnosing a neurological dysfunction in the early stages of infancy. One study has shown that definitely abnormal movements occurring between 10-20 weeks post-term accurately predicted cerebral palsy in infants with an accuracy of 85 to 98 percent [1]. The qualitative method of assessing an infant's GMs is an accurate way of predicting a neurological dysfunction, however, requires the review of hours of video footage by a trained physician. This process is not only time consuming and costly but is subjective in the sense that the results cannot be easily transferred among different institutions. It is also difficult to conduct longitudinal studies without first reviewing the entire history of video footage of the infant's GMs. Improvements can be made to the qualitative GMs assessment method by utilizing recent advances in technology that "can make data collection and analysis more efficient, without compromising competency" [2]. In particular, preliminary research has shown that data collected from"wired" micro-electrical-mechanical systems (MEMS) accelerometers attached to the wrist and ankles of an infant is a feasible way of collecting and characterizing the motion patterns that infants display during GMs [3]. The work presented in this thesis is directed towards improving the past research that used "wired" accelerometers to acquire acceleration signals from the limbs of infants. This thesis describes the process of transitioning the "wired" accelerometers to the wireless level, designing a user-friendly interface to graphically interpret the acceleration data, and assessing the designed system through clinical trials on normal and at-risk infants using the design system. / Master of Science

Background: The optimal timing of surgical therapy for traumatic spinal cord injury (TSCI) remains unclear. The purpose of this study is to evaluate the impact of “ultra-early” (<4 h) versus “early” (4–24 h) time from injury to surgery in terms of the likelihood of neurologic recovery. Methods: The effect of surgery on neurological recovery was investigated by comparing the assessed initial and final values of the American Spinal Injury Association (ASIA) Impairment Scale (AIS). A post hoc analysis was performed to gain insight into different subgroup regeneration behaviors concerning neurological injury levels. Results: Datasets from 69 cases with traumatic spinal cord injury were analyzed. Overall, 19/46 (41.3%) patients of the “ultra-early” cohort saw neurological recovery compared to 5/23 (21.7%) patients from the “early” cohort (p = 0.112). The subgroup analysis revealed differences based on the neurological level of injury (NLI) of a patient. An optimal cutpoint for patients with a cervical lesion was estimated at 234 min. Regarding the prediction of neurological improvement, sensitivity was 90.9% with a specificity of 68.4%, resulting in an AUC (area under the curve) of 84.2%. In thoracically and lumbar injured cases, the estimate was lower, ranging from 284 (thoracic) to 245 min (lumbar) with an AUC of 51.6% and 54.3%. Conclusions: Treatment within 24 h after TSCI is associated with neurological recovery. Our hypothesis that intervention within 4 h is related to an improvement in the neurological outcome was not confirmed in our collective. In a clinical context, this suggests that after TSCI there is a time frame to get the right patient to the right hospital according to advanced trauma life support (ATLS) guidelines.

Funktionella neurologiska symtom är vanliga och funktionsnedsättande symtom som ofta anses svårbehandlade. En vanlig förklaringsmodell har varit att den drabbade varit med om något stressande och traumatiskt som lett till kroppsliga symtom. Denna förklaringsmodell leder till frågan om psykologisk behandling med fokus på trauma kan påverka funktionella neurologiska symtom. En systematisk litteraturöversikt, i enlighet med riktlinjer från Statens beredning för medicinsk och social utvärdering, har genomförts för att undersöka om psykologisk traumabehandling med kognitiv beteendeterapi och Eye Movement Desensitization and Reprocessing Therapy kan minska funktionella neurologiska symtom vid symtom på komorbid posttraumatiskt stressyndrom. Resultaten av litteraturöversikten består av totalt 10 artiklar, merparten fallstudier. Slutsatsen av litteraturöversikten tyder på att den forskning som gjorts visar på minskning av funktionella neurologiska symtom efter behandling av symtom på posttraumatiskt stressyndrom. Detta forskningsområde är dock väldigt litet och består främst av fallstudier med något bristande kvalitet. Trots detta anser vi att det finns underlag för att rekommendera att det bör finnas ett fokus på erfarenheter av trauma vid bedömning av funktionella neurologiska symtom.

Injuries to the brain are the leading cause of permanent disability and death. Survivors of acquired brain injury (ABI) experience cognitive impairments and emotional problems. These often persist into community rehabilitation and are among the most significant needs for those in chronic stages of rehabilitation. There is a dearth of research providing evidence of music therapy addressing cognitive deficits and emotional needs in a holistic approach. This research answers the question how can brief group music therapy address cognitive functional gains and emotional needs of people with acquired brain injury. A mixed methods design was used to investigate the effect of 16 sessions of weekly group music therapy on attention and memory impairments, and emotional needs of ten ABI survivors in community rehabilitation. Quantitative data were collected to determine the effect of treatment on attention and memory functioning, mood state, and the satisfaction of emotional needs. Qualitative data were collected to reveal survivors’ experiences of brain injury and brief group music therapy. Analysis of the data showed that the intervention improved sustained attention (p<.05, r=.80) and immediate memory recall (p>.05, r=.46), and that the effect of treatment increased with dosage. Overall, the intervention was more effective than standard care, and cognitive functional gains continued after treatment for some ABI survivors. The intervention addressed emotional needs of feeling confident (p<.05, d=.88), feeling part of a group (p<.05, d=.74), feeling productive/useful (p<.05, d=.90), feeling supportive (p<.05, d=.75), feeling valued (p<.05, d=.74), and enjoyment (p<.05, d=.34). Improvements in these domains were observed in the immediate term and over the course of therapy. Music therapy enabled emotional adjustment through the development of selfawareness and insight. This study offers a music therapy method to deliver a holistic approach in rehabilitation. It demonstrates that music therapy can provide a cost effective, holistic treatment for ABI survivors.

Prior work in our lab has indicated that reduced Hydroxocobalamin (B12r) can be added to human blood and is able to convert carbon monoxide (CO) into carbon dioxide. This has great potential as a direct antidote to mitigate the toxic effects of CO poisoning which is a public health risk. In the first part of our work, we use highly specific wavelengths of light and Raman spectroscopy to study changes in Carboxyhemoglobin (COHb) between blood treated with oxygen and blood treated with oxygen and B12r in a flowing circuit of blood. Using Raman spectroscopy, we found that the addition of B12r hastens the conversion of the COHb Raman signals to Oxyhemoglobin (HbO2) Raman signals. In addition, the B12r absorbance of light energy within the Raman spectrum is an exploitable relationship that can be used to measure B12r presence in the blood. In part two of our study we focused on the neurobehavioral testing of rats injured by CO exposure, however, we were not able to find statistical differences in the behavioral tests between exposed and unexposed rats.