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Down syndrome (DS) is a common genetic developmental disorder characterized by the trisomy of chromosome 21 (Hsa21). All individuals with DS have some kind of intellectual disability, associated with dysfunction in cognition-related structures, including the frontal cortex. Studies have examined developmental changes in the frontal cortex during prenatal stages in

Down syndrome (DS) is a common genetic developmental disorder characterized by the trisomy of chromosome 21 (Hsa21). All individuals with DS have some kind of intellectual disability, associated with dysfunction in cognition-related structures, including the frontal cortex. Studies have examined developmental changes in the frontal cortex during prenatal stages in DS, however little is known about cortical lamination and neuronal differentiation in postnatal periods in this neurodevelopmental disorder. Therefore, we examined the quantitative and qualitative distribution of neuronal profiles containing the neuronal migration protein doublecortin (DCX), the non-phosphorylated high-molecular-weight neurofilament SMI-32, the calcium-binding proteins calbindin D-28K (Calb), calretinin (Calr), and parvalbumin (Parv), as well as human β-amyloid and APP (6E10), Aβ1-42, and phospho-tau (CP-13) in the supragranular (SG, II/III) and infragranular (IG, V/VI) layers in the DS postnatal frontal cortex compared to neurotypically developing (NTD) controls from ages 28 weeks to 196.4 weeks using immunohistochemistry. Furthermore, cortical lamination was evaluated using thionin, a Nissl stain. We found DCX-immunoreactive (-ir) cells in both the SG and IG layers in younger cases, but not in the oldest cases in both groups. Strong expression of SMI-32 immunoreactivity was observed in pyramidal cells in layers III and V in the oldest cases in both groups, however SMI-32-ir cells appeared much earlier in NTD compared to DS. We found small and fusiform Calb-ir cells in the younger cases (28 to 44 weeks), while in the oldest cases, Calb immunoreactivity was also found in pyramidal cells. Calr-ir cells appeared earlier in DS at 32 weeks compared to NTD at 44 weeks, however both groups showed large bipolar fusiform-shaped Calr-ir cells in the oldest cases. Diffuse APP/Aβ-ir plaque-like accumulations were found in the frontal cortex grey and white matter at all ages, but no Aβ1-42 immunoreactivity was detected in any case. Furthermore, neuropil (but not cellular) granular CP-13 immunostaining was seen in layer I only at 41 weeks NTD and 33 weeks DS. Cell counts show a significantly higher cell number in SG compared to IG for all the neuronal markers in both groups, except in Calb and SMI-32. In NTD, age and brain weight showed the strongest correlations with all cellular counts, except in thionin where DS had a stronger negative correlation with age and brain weight compared to NTD. In addition, height and body weight showed a strong negative correlation in NTD with the migration and neurogenesis marker DCX. These findings suggest that trisomy 21 affects the postnatal frontal cortex lamination, neuronal migration<br/>eurogenesis, and differentiation of projection pyramidal cells and interneurons, which contribute to the disruption of the local and projection inhibitory and excitatory circuitries that may underlie the cognitive disabilities in DS.

ContributorsUtagawa, Emma Christina (Author) / Penkrot, Tonya (Thesis director) / Perez, Sylvia (Committee member) / Shafernak, Kristian (Committee member) / College of Health Solutions (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a

The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a tumor, as a tumor cannot grow larger than 1-2 mm3 without developing its own blood supply. Vascular disrupting agents, such as iodocombstatin, a derivative of combretastatin, can be used to effectively cut off the blood supply to a growing neoplasm, effectively inhibiting the supply of oxygen and nutrients needed for cell division Thus, VDAs have a very important implication in terms of the future of chemotherapy. A prodrug, defined as an agent that is inactive in the body until metabolized to yield the drug itself, was synthesized by combining iodocombstatin with a β-glucuronide linker. The prodrug is theoretically hydrolyzed in the body to afford the active drug by β-glucuronidase, an enzyme that is produced five times as much by cancer cells as by normal cells. This effectively creates a “magic-bullet” form of chemotherapy, known as Direct Enzyme Prodrug Therapy (DEPT).
ContributorsClark, Caroline Marie (Author) / Pettit, George Robert (Thesis director) / Melody, Noeleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
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Description

Down syndrome (DS) is caused by either an extra copy of chromosome 21 or by extra material on chromosome 21. This causes various levels of intellectual disability and issues with gross motor skill development which can prevent these individuals from participating in activities of daily living (ADL) such as getting

Down syndrome (DS) is caused by either an extra copy of chromosome 21 or by extra material on chromosome 21. This causes various levels of intellectual disability and issues with gross motor skill development which can prevent these individuals from participating in activities of daily living (ADL) such as getting dressed, self-care, or grocery shopping. People with DS have a decreased ability to balance, an abnormal and slower gait pattern, difficulty adapting to new environments, and a lack of improvement in these areas with growth and development when compared to their neurotypical peers. The objective of this study was to determine the immediate effects of resistance training (RT) and assisted cycle therapy (ACT) on adults with DS’s balance ability and gait speed. Each participant completed one session of RT, ACT (stationary cycling with the assistance of a motor to maintain a cadence of at least 35% greater than their voluntary cycling speed), and no training in a randomly selected order. Balance and gait speed were measured by a Clinical Test of Sensory Interaction on Balance (CTSIB) (i.e., eyes open firm surface, eyes closed firm surface, eyes open foam surface, eyes closed foam surface) on a Balance Tracking System Board (Btracks board) and by a Timed Up and Go (TUG) test. A total of ten participants’ data was used for analysis. The measures of total path length (cm), anterior-posterior (AP) excursion, and medial-lateral (ML) excursion were used to analyze the CTSIB. The average time was used to analyze the TUG test. The results showed that the eyes closed foam surface balance task was the most challenging balance task for every participant in every intervention. Furthermore, the most improvement was evident in the eyes closed foam surface balance task from pre to post intervention in all of the interventions. Post hoc tests also indicated statistically significant improvements of path length from pre to post in the RT intervention with the eyes closed foam surface balance task as well as with AP excursion in the ACT intervention with the eyes closed foam surface balance task. Possible explanations for improvements from pre to post in the eyes closed foam balance task across all interventions will be discussed with respect to the length of the intervention, and the effect of strength, social and learned factors on balance in adults with DS.

ContributorsKeim, Jeannette Danielle (Author) / Ringenbach, Shannon (Thesis director) / Peterson, Daniel (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
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Small cell carcinoma of the ovary (SCCOHT) is a rare ovarian cancer affecting young women and characterized by mutation in SMARCA4 and silencing of SMARCA2, two tumor suppressors that function as ATPases in the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. SCCOHT patients face a 5-year survival rate of only 26%,

Small cell carcinoma of the ovary (SCCOHT) is a rare ovarian cancer affecting young women and characterized by mutation in SMARCA4 and silencing of SMARCA2, two tumor suppressors that function as ATPases in the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. SCCOHT patients face a 5-year survival rate of only 26%, but recently we have identified sensitivity of SCCOHT models to a natural product, triptolide. This study aims to ascertain the mechanism of action of triptolide. Previous SCCOHT epigenetic drug research has shown that some drugs reverse SMARCA2 epigenetic silencing to inhibit tumor growth, therefore it is hypothesized that triptolide acts the same and restores SWI/SNF function. Cells treated with triptolide have no change in SMARCA2 expression, suggesting that re-expression of epigenetically silenced tumor suppressor gene does not underlie its mechanism of action. Growth rates following triptolide treatment were observed in the presence and absence of SMARCA4, but no difference in sensitivity was observed. Thus, it is not likely that triptolide acts by restoring SWI/SNF. Others have observed that triptolide acts on xeroderma pigmentosa type B protein (XPB), a component of super-enhancers, which are DNA regions with high levels of transcription that regulate genes responsible for cell identity and oncogenes driving tumorigenesis. Both SCCOHT-1 and BIN67 cell lines treated with triptolide displayed lower expression of the super-enhancer associated MYC oncogene compared to untreated cells, supporting the theory that triptolide could be inhibiting super-enhancers regulating oncogenes.. A western blot confirmed reduced protein levels of RNA polymerase II and bromodomain 4 (BRD4), two essential components found at high levels at super-enhancers, in BIN67 cells treated with triptolide. ChIP-sequencing of Histone H3 Lysine-27 Acetylation (H3K27ac) marks in BIN67 and SCCOHT-1 cell lines identified super-enhancers in SCCOHT using tools CREAM and ROSE, which were mapped to neighboring genes associated genes and compared with the COSMIC database to identify oncogenes, of which the top 11 were examined by qRT-PCR to ascertain whether triptolide reduces their expression. It has been found that 6 out of 11 of the oncogenes examined (SALL4, MYC, SGK1, HIST1H3B, HMGA2, and CALR) decreased in expression when treated with triptolide. Thus, there is reason to believe that triptolide’s mechanism of action is via inhibition of super-enhancers that regulate oncogene expression.
ContributorsViloria, Nicolle Angela (Author) / Lake, Douglas (Thesis director) / Hendricks, William (Committee member) / Lang, Jessica (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
Estimates indicate that in the United States 1 in 8 women will develop breast cancer in their lifetime. Improved cancer screenings, early detection, and targeted treatments have increased breast cancer survival rates. However, breast cancer patients treated with chemotherapy are at an increased risk for cardiovascular disease, functional impairments, and

Estimates indicate that in the United States 1 in 8 women will develop breast cancer in their lifetime. Improved cancer screenings, early detection, and targeted treatments have increased breast cancer survival rates. However, breast cancer patients treated with chemotherapy are at an increased risk for cardiovascular disease, functional impairments, and loss of cardiorespiratory fitness. These negative outcomes have implications for early morbidity and mortality. The purpose of this thesis was to test the hypothesis that high-intensity exercise preconditioning (exercise commenced prior to initiating chemotherapy and continued throughout treatment cycles) preserves health-related outcomes in breast cancer patients treated with anthracycline-containing chemotherapy. Here, we present a subset of preliminary data from an ongoing trial (NCT02842658) that is focused on VO2peak and skeletal muscle outcomes from the first 10 participants that have enrolled in the trial. Breast cancer patients (N=10; 50 ± 11 y; 168 ± 4 cm; 92 ± 37 kg; 32.3 ± 12.3 kg/m2) scheduled to receive anthracycline-containing chemotherapy were randomly assigned to one of two interventions: 1) exercise preconditioning, (3 days per week of supervised exercise throughout treatment) or 2) standard of care (attention-control). Pre-testing occurred 1-2 week prior to chemotherapy. The interventions were initiated 1 week prior to chemotherapy and continued throughout anthracycline treatment. Post-testing occurred 3-7 days following the last anthracycline treatment. VO2peak (L/min) was reduced by 16% in the control group (P < 0.05), whereas VO2peak was preserved in the exercise preconditioning group. Trends for greater preservation and/or improvement in the exercise preconditioning group were also observed for lean body mass and peak heart rate. Hand grip strength was not changed in either group (P > 0.05). Both groups demonstrated an increase in ultrasound-derived echogenicity measures of the vastus lateralis (P < 0.05), indicating changes in the composition of the skeletal muscle during treatment. These preliminary data highlight that exercise preconditioning may serve as a strategy to preserve cardiorespiratory fitness and perhaps lean mass during anthracycline treatment of breast cancer. There remains a need for larger, definitive clinical trials to identify strategies to prevent the array of chemotherapy-induced toxicities that are observed in breast cancer patients treated with anthracyclines.
ContributorsCasey, Kathleen (Author) / Angadi, Siddhartha (Thesis director) / Gaesser, Glenn (Committee member) / Dickinson, Jared (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The genetic disorder Down syndrome (DS), clinically known as Trisomy 21, is characterized by the presence of either a part or full extra copy of chromosome 21. When compared with children of typical development, children with DS consistently score lower on gross motor skill tasks. Balance specifically is one of

The genetic disorder Down syndrome (DS), clinically known as Trisomy 21, is characterized by the presence of either a part or full extra copy of chromosome 21. When compared with children of typical development, children with DS consistently score lower on gross motor skill tasks. Balance specifically is one of the hardest skills for individuals with DS (especially children) to acquire, and neglecting to train balance early on can predispose individuals with DS to further movement instabilities, injuries, social struggles from activity limitations, and an overall lack of independence. One of the more unique forms of physical activity that requires a large amount of both static and dynamic balance is ballet. Dance-specific therapy has been shown to improve gross motor control functioning and specifically balance in a variety of populations with neuromuscular condions, but the research around ballet-specific therapy for those with DS is lacking. The purpose of this pilot study was to further investigate the effects of ballet-specific training on balance ability and general motor functioning in young students with DS as measured by the Four Square Step Test (FSST), Pediatric Balance Scale (PBS), and the gross and fine motor domains of the Vineland Adaptive Behavior Scale lll (VABS lll). It was hypothesized that participation in the 6-week summer cohort of Ballet Arizona’s Adaptive Dance Program would lead to improved scores on the PBS and VABS lll and decreased test times in the FSST. Improvements were observed for all measures for both participants (sample size n=2), except for P1's FSST, which increased in post-testing by 2.25s. Due to the study design, no conclusive statements can be made about whether the ballet program was responsible for the improvements observed in post-testing. More rigorous research with larger sample sizes (>30) is warranted to more fully understand the impact of an adapted ballet program on the balance ability of young individuals with DS. However, the program is still recommended for young individuals with DS because of the benefits it provides outside of motor skill development.
ContributorsMitrovic, Jelena (Author) / Peterson, Daniel (Thesis director) / Holzapfel, Simon (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2022-12
Description

Accessing adequate healthcare, particularly essential services like physical therapy, presents a significant challenge for individuals with Down syndrome. This demographic often encounters obstacles such as limited accessibility, scarce resources, and a lack of tailored solutions that specifically address their unique needs. The resulting disparity leads to inconsistent care and suboptimal

Accessing adequate healthcare, particularly essential services like physical therapy, presents a significant challenge for individuals with Down syndrome. This demographic often encounters obstacles such as limited accessibility, scarce resources, and a lack of tailored solutions that specifically address their unique needs. The resulting disparity leads to inconsistent care and suboptimal healthcare experiences. Recognizing the importance of eliminating these barriers is crucial to create a more inclusive healthcare environment for individuals with Down syndrome. Rainbow Monster Madness serves as a multifaceted solution to the social determinants of health that significantly impact individuals with Down syndrome. The game's design directly tackles several of these determinants by offering accessible, engaging, and family-centered therapy. In terms of healthcare access and quality, the game empowers parents to actively participate in their child's therapy, ensuring the correct administration of exercises and the consistent provision of quality care. The game's design addresses neighborly and built environment determinants by providing an accessible and inclusive therapy option that can be implemented within the comfort of one's home. This approach fosters a sense of safety and familiarity for children undergoing therapy, promoting a more relaxed and conducive environment. Additionally, Rainbow Monster Madness encourages social community engagement by fostering a collaborative atmosphere between parents and children during therapy sessions. This collaborative approach creates a supportive and engaging environment, positively impacting the overall therapeutic experience. Adhering to the principles of Self-Determination Theory, the game cultivates intrinsic motivation and psychological well-being among children with Down syndrome. This approach enables active engagement in therapy and contributes to their overall health and well-being. The exercises included in Rainbow Monster Madness are carefully selected to cater to the unique needs of individuals with Down syndrome. This regimen combines muscle-strengthening, cardio, and balance exercises, tailored to this specific population. The modification of exercises and thematic design ensures that children remain enthusiastic about their therapy, ultimately promoting better adherence and more effective results. In summary, Rainbow Monster Madness represents a comprehensive solution to the multitude of challenges faced by individuals with Down syndrome in accessing healthcare. Simultaneously, it addresses the broader social determinants of health, thereby fostering a healthier and more inclusive future for this deserving population.

ContributorsAnderson, Lyndsey (Author) / Montalvo, Alicia (Thesis director) / Miossi, Lindsey (Committee member) / Hoffner, Kristin (Committee member) / Barrett, The Honors College (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / College of Health Solutions (Contributor)
Created2023-12
Description

Research has shown the benefits of exercise on people with (DS), and how it affects their quality of life (Maïano et al. 2019). However, many studies have also shown that the majority of people with DS do not meet the national minimum requirements for physical activity per day (Phillips et

Research has shown the benefits of exercise on people with (DS), and how it affects their quality of life (Maïano et al. 2019). However, many studies have also shown that the majority of people with DS do not meet the national minimum requirements for physical activity per day (Phillips et al. 2011). The current study will focus on Pediatric Assisted Cycle Therapy (PACT) as exercise and specifically its effects on children with DS. The goal is to improve the general behavioral skills of children with DS, which in turn can improve their quality of life. We predict that, based on pilot data (Gomez, 2015; Parker, 2016), GLTEQ will increase their total activity score following 8 weeks of PACT in young children with DS. The Godin Leisure Time Exercise Questionnaire was used to measure the participants’ participation levels in leisure time activity. Participants were involved in an 8-week intervention, in which they biked (PACT) for 30 minutes, twice a week. GLETQ was measured pre and post intervention and assessed using the scale provided by the GLETQ. The data from this study has shown a positive correlation between Leisure Time Activity and PACT. Overall, a mean increase in raw activity score in the GLETQ was shown.

ContributorsGonzalez, Xavier (Author) / Ringenbach, Shannon (Thesis director) / Ofori, Edward (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2023-05
Description
Many children with disabilities need physical therapy treatment but it can be difficult to instruct patients with restricted or limited communication. Most exercise cards and depictions used in communicating instruction to pediatric special needs patients are not representative of children with disabilities. This project aimed to create inclusive physical therapy

Many children with disabilities need physical therapy treatment but it can be difficult to instruct patients with restricted or limited communication. Most exercise cards and depictions used in communicating instruction to pediatric special needs patients are not representative of children with disabilities. This project aimed to create inclusive physical therapy exercise cards depicting children with disabilities. The goal of these cards was to help communicate instructions and motivate children to perform their exercises in clinical settings. The exercise selection was based on observations from working with children with disabilities in a pediatric physical therapy clinic. As a result, photos of children with developmental disabilities were taken performing exercises and subsequently made into cards and provided to physical therapists (PT). The PT’s used the cards for at least a week and reported on their functionality. The feedback from PT’s regarding the use of exercise cards in therapy sessions was overwhelmingly positive. With the positive feedback from the PT’s, the cards will be published and donated to pediatric physical therapy clinics in Arizona.
ContributorsMack, Sarah (Author) / Hart, Teresa (Thesis director) / Broman, Tannah (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2024-05
Description
Financial toxicity is a term that has gained traction within the oncology field, detailing the financial burden on and distress of cancer patients in regard to their cancer regimen and treatment. Previous research has shown that financial toxicity affects older cancer patients, but more recent research has shown that it

Financial toxicity is a term that has gained traction within the oncology field, detailing the financial burden on and distress of cancer patients in regard to their cancer regimen and treatment. Previous research has shown that financial toxicity affects older cancer patients, but more recent research has shown that it can affect anyone of any demographic, particularly newly diagnosed cancer patients. Unfortunately, patients may not fully understand the costs associated with cancer treatment, which can make it difficult for them to effectively contain the costs. This issue has been ongoing and will continue to affect many as cancer treatment evolves with developments in technology and medications and more patients survive. Due to the financial distress, patients can make alterations to their healthcare and treatment, potentially resulting in the decline of patients’ quality of life and possible worsening of cancer outcomes. The present problem of financial toxicity was examined and compiled into a website, where the information was organized into different pages for ease of reading and additional resources were provided. This website is currently ready for use, but I hope to continue improving it with additional information and resources.
ContributorsNguyen, Kaitlyn Nhi (Author) / O'Flaherty, Katherine (Thesis director) / Anbar, Joshua (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2024-05