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- All Subjects: Mental Health
- All Subjects: Cancer
- Creators: Barrett, The Honors College
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Resource Type: Text
- Status: Published
Description
A major challenge with tissue samples used for biopsies is the inability to monitor their molecular quality before diagnostic testing. When tissue is resected from a patient, the cells are removed from their blood supply and normal temperature-controlled environment, which causes significant biological stress. As a result, the molecular composition and integrity undergo significant change. Currently, there is no method to track the effects of these artefactual stresses on the sample tissue to determine any deviations from the actual patient physiology. Without a way to track these changes, pathologists have to blindly trust that the tissue samples they are given are of high quality and fit for molecular analysis; physicians use the analysis to make diagnoses and treatment plans based on the assumption that the samples are valid. A possible way to track the quality of the tissue is by measuring volatile organic compounds (VOCs) released from the samples. VOCs are carbon-based chemicals with high vapor pressure at room temperature. There are over 1,800 known VOCs within humans and a number of these exist in every tissue sample. They are individualized and often indicative of a person’s metabolic condition. For this reason, VOCs are often used for diagnostic purposes. Their usefulness in diagnostics, reflectiveness of a person’s metabolic state, and accessibility lends them to being beneficial for tracking degradation. We hypothesize that there is a relationship between the change in concentration of the volatile organic compounds of a sample, and the molecular quality of a sample. This relationship is what would indicate the accuracy of the tissue quality used for a biopsy in relation to the tissue within the body.
ContributorsSharma, Nandini (Co-author) / Fragoso, Claudia (Co-author) / Grenier, Tyler (Co-author) / Hanson, Abigail (Co-author) / Compton, Carolyn (Thesis director) / Tao, Nongjian (Committee member) / Moakley, George (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
By 2030, the number of people above the age of 65 is projected to outnumber those under the age of 18 for the first time in United States history. With a growing older population, it is predicted that the amount of people moving into nursing homes and care facilities will also increase. However, a pressing problem is the high prevalence of depression and anxiety among elderly people residing in institutionalized living arrangements. With drugs and antidepressants less effective at treating patients with both dementia and depression, there is a need for more non-pharmacological interventions geared toward improving older adults’ mental well-being. In response, the potential therapeutic effect of exploring virtual nature through EcoRift—which provides dynamic and realistic 360-degree audio and visual environments—on older adults’ mental well-being was examined in this study. Ten individuals (3 men and 7 women) aged 50 and above were recruited and each participant experienced the virtual nature sojourns for 15 minutes once a week, for a total of three weeks. Pre- and post- virtual reality (VR) survey questionnaires were implemented to gauge the participants’ emotional response, including overall well-being and level of relaxation. Physiological measures such as heart rate and blood pressure were also taken before and after the VR experience. Findings show that immersion in nature through virtual reality improves older adults’ mental well-being by eliciting a transient sense of relaxation, peacefulness, and happiness. Further studies need to be performed in order to validate EcoRift’s effect on physiology; however, preliminary data suggests that immersive virtual nature also acts to decrease blood pressure. Overall, EcoRift shows to be a promising tool for bridging access to remote natural environments and may be a mentally beneficial activity for patients isolated in hospitals, hospices, and nursing homes.
ContributorsChien, Naomi Wei-Chia (Author) / Feisst, Sabine (Thesis director) / Cordes, Colleen (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
In cancer, various genetic and epigenetic alterations cause cancer cells to hyperproliferate and to bypass the survival and migration mechanisms that typically regulate healthy cells. The focal adhesion kinase (FAK) gene produces FAK, a protein that has been implicated in tumor progression in various cancers. Compared with normal tissue counterparts, FAK is overexpressed in many cancers. FAK is therefore a promising cancer drug target due to its demonstrated role in cancer invasion and metastasis and inhibition of FAK is important to achieve an optimal tumor response. Small molecule FAK inhibitors have been shown to decrease tumor growth and metastasis in several preclinical trials. However, these inhibitors focus narrowly on the enzymatic portion of FAK and neglect its scaffolding function, leaving FAK’s scaffolding of oncogenic drivers intact. Paxillin, a major focal adhesion-associated protein, binds to FAK, enabling it to localize to focal adhesions, and this is essential for FAK’s activation and function. Therefore, disrupting the protein-protein interaction between FAK and paxillin has been hypothesized to prevent tumor progression. The binding of FAK to paxillin at its focal adhesion targeting (FAT) domain is mediated by two highly conserved leucine-rich sequences, the leucine-aspartic acid (LD) motifs LD2 and LD4. The purpose of this project was to develop novel stapled LD2 peptide analogs that target the protein-protein interaction of FAT to LD2. Peptide stapling was performed to enhance the pharmacological performance of the LD2 peptide analogs. Based on the native LD2 peptide sequence, stapled LD2 peptide analogs were developed with the intent to improve efficacy of cell permeability, while maintaining or improving FAK binding. The LD2 peptide analogs were characterized via surface plasmon resonance, fluorescence polarization, immunofluorescence, and circular dichroism spectroscopy. Successful LD2 stapled peptide analogs can be therapeutically relevant inhibitors of the FAT-LD2 protein-protein interaction in cancer and have the potential for greater efficacy in FAK inhibition, proteolytic resistance, and cell permeability, which is key in preventing tumor progression in cancer.
ContributorsNott, Rohini (Author) / Gould, Ian R. (Thesis director) / Marlowe, Timothy A. (Committee member) / Cance, William G. (Committee member) / School of Life Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Cytokines induced by inflammasome has been used for blood cancer treatments, yet these treatments have been less successful in the solid tumor microenvironment. Here precise-morphology DNA origami structures were implemented to accurately test the effect and mechanism of activation in the NLRP3 inflammasome. THP1 WT cells, a macrophage cell line, were treated with eleven different DNA origami structures. The inflammasome activation of two cytokines, Interleukin 1 beta (IL-1β) and Interferon beta (IFN-β), was measured using HEK Blue IL-1β cells, HEK Blue IFN-β cells, and enzyme linked immunosorbent assay (ELISA). Differences in activation signaling have the potential to provide the characterization required to address the intrinsic complexity of modulating an immune response. It is hoped that DNA origami will help induce more inflammation for solid tumors. The DNA origami was tested in three different volumes: 1 μL, 5 μL, and 10 μL. Overall, the origami that showed promising results were Mg Square. Tetrahedral and P53 block also showed potential but not as well as Mg square. Further testing of more DNA origami structures and testing them in mice are key to the success of targeted cancer immunotherapies in the neoadjuvant setting.
ContributorsGreenwald, Elinor Vera (Co-author) / Ariola, Amanda (Co-author) / Ning, Bo (Thesis director) / Zhang, Fei (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This study examines the intersectionality of mental health and education, with an emphasis on resources and awareness for elementary school teachers. It starts with a review of mental health awareness in society, particularly in regard to social stigma and its associated effects. I then discuss the existing resources, teaching methods, and third party interventions which address mental health awareness and care within elementary schools. Within this context, the research supports the strong influence of teachers’ behaviors and perceivable attitudes on students. However, despite the identification of teachers playing a significant role in the availability of mental health resources for students, existing studies rarely addresses the necessity of mental health awareness and care to optimize teacher capacity and counteract occupational stress. The study examines the current approach and challenges of an elementary school that has expressed interest in creating a culture of care, characterized by mental health awareness and resources that support teachers within the school environment. After identifying the key mental health concerns of the school’s stakeholders, I propose a custom program of self-care and mental health awareness to support the current work culture. The study concludes with examination of implementation strategies for the school, as well as implications for future mental health awareness in similar settings.
ContributorsGiles, Emma (Author) / Johnston, Erik W., 1977- (Thesis director) / Hinrichs, Margaret (Committee member) / Desch, Timothy (Committee member) / Dean, W.P. Carey School of Business (Contributor, Contributor) / School of Public Affairs (Contributor) / Department of Management and Entrepreneurship (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Children with cancer can experience decreased emotional health along with deteriorating
physical health compared to children without cancer. Many studies have been done to examine the effects of emotional distress and mental health on the cancer patient, as well as the role of familial support. It was found that children with cancer may suffer from depression, anxiety, PTSD, and socio-emotional problems as a result of the trauma of being diagnosed and treated for a pervasive, life-threatening disease. Late effects may also worsen co-morbid mental health disorders. Childhood cancer patients who experience co-morbid mental health problems of depression and anxiety end up having a longer duration of recovery, as well as a worsened outcome than others with a single disorder (Massie, 2004). It was also shown that family members are affected emotionally and mentally from dealing with childhood cancer. Not only is the cancer patient at risk for PTSD during or after treatment, but also family members (National Cancer Institute, 2015). Siblings of the child with cancer may experience feelings of loneliness, fear, and anxiety, as the parent’s attention is focused on the child suffering with cancer. According to the National Cancer Institute (2015), familial problems can affect the child’s ability to adjust to the diagnosis and treatment in a positive way. However, children with strong familial and social support adjust easier to living with cancer. A common theme found in literature is that regular mental health checkups during and after cancer treatment is important for quality of life. Therefore, it is important for all childhood cancer patients and their families to receive information about mental health awareness, as well as therapeutic interventions that are developed for families caring for a child with cancer.
physical health compared to children without cancer. Many studies have been done to examine the effects of emotional distress and mental health on the cancer patient, as well as the role of familial support. It was found that children with cancer may suffer from depression, anxiety, PTSD, and socio-emotional problems as a result of the trauma of being diagnosed and treated for a pervasive, life-threatening disease. Late effects may also worsen co-morbid mental health disorders. Childhood cancer patients who experience co-morbid mental health problems of depression and anxiety end up having a longer duration of recovery, as well as a worsened outcome than others with a single disorder (Massie, 2004). It was also shown that family members are affected emotionally and mentally from dealing with childhood cancer. Not only is the cancer patient at risk for PTSD during or after treatment, but also family members (National Cancer Institute, 2015). Siblings of the child with cancer may experience feelings of loneliness, fear, and anxiety, as the parent’s attention is focused on the child suffering with cancer. According to the National Cancer Institute (2015), familial problems can affect the child’s ability to adjust to the diagnosis and treatment in a positive way. However, children with strong familial and social support adjust easier to living with cancer. A common theme found in literature is that regular mental health checkups during and after cancer treatment is important for quality of life. Therefore, it is important for all childhood cancer patients and their families to receive information about mental health awareness, as well as therapeutic interventions that are developed for families caring for a child with cancer.
ContributorsBuchanan, Chantel Tatiana (Author) / Seeley, Bridget (Thesis director) / Bradley, Robert (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Fusion protein immunotherapies such as the bispecific T cell engager (BiTE) have displayed promising potential as cancer treatments capable of engaging the immune system against tumor cells. It has been shown that chlorotoxin, a 36-amino peptide found in the venom of the deathstalker scorpion (Leiurus quinquestriatus), binds specifically to glioblastoma (GBM) cells without binding healthy tissue, making it an ideal GBM cell binding moiety for a BiTE-like molecule. However, chlorotoxin’s four disulfide bonds pose a folding challenge outside of its natural context and impede production of the recombinant protein in various expression systems, including those relying on bacteria and plants. To overcome this difficulty, we have engineered a truncated chlorotoxin variant (Cltx∆15) that contains just two of the original eight cystine residues, thereby capable of forming only a single disulfide bond while maintaining its ability to bind GBM cells. We further created a BiTE (ACDClx∆15) which tethers Cltx∆15 to a single chain ⍺-CD3 antibody in order to bring T cells into contact with GBM cells. The gene for ACDClx∆15 was cloned into a pET-11a vector for expression in Escherichia coli and isolated from inclusion bodies before purification via affinity chromatography. Immunoblot analyses confirmed that ACDClx∆15 can be expressed in E. coli and purified with high yield and purity; moreover, flow cytometry indicated that ACDClx∆15 is capable of binding GBM cells. These data warrant further investigation into the ability of ACDClx∆15 to activate T cells against GBM cells.
ContributorsSchaefer, Braeden Scott (Author) / Mor, Tsafrir (Thesis director) / Mason, Hugh (Committee member) / Cook, Rebecca (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Colorectal cancer is the third most common type of cancer that affects both men and women and the second leading cause of death in cancer related deaths[1, 2]. The most common form of treatment is chemotherapy followed by radiation, which is insufficient to cure stage four cancers[3]. Salmonella enteric has long been shown to have inherent tumor targeting properties and have been able to penetrate and exist in all aspects of the tumor environment, something that chemotherapy is unable to achieve. This lab has developed a genetically modified Salmonella typhimurium (GMS) which is able to deliver DNA vaccines or synthesized proteins directly to tumor sites. These GMS strains have been used to deliver human TNF-related apoptosis inducing ligand (TRAIL) protein directly to tumor sites, but expression level was limited. It is the hope of the experiment that codon optimization of TRAIL to S. typhimurium preferred codons will lead to increased TRAIL expression in the GMS. For preliminary studies, BALB/c mice were subcutaneously challenged with CT-26 murine colorectal cancer cells and treated with an intra-tumor injection with either PBS, strain GMS + PCMV FasL (P2), or strain GMS + Pmus FasL). APC/CDX2 mutant mice were also induced to develop human colon polyps and treated with either PBS, strain GMS + vector (P1), P2, or P3. The BALB/c mouse showed statistically significant levels of decreased tumor size in groups treated with P2 or P3. The APC/CDX2 mouse study showed statistically significant levels of decreased colon polyp numbers in groups treated with P3, as expected, but was not significantly significant for groups treated with P1 and P2. In addition, TRAIL was codon optimized for robust synthesis in Salmonella. The construct will be characterized and evaluated in vitro and in vivo. Hopefully, the therapeutic effect of codon optimized TRAIL will be maximal while almost completely minimizing any unintended side effects.
ContributorsCrawford, Courtney Rose (Co-author) / Crawford, Courtney (Co-author) / Kong, Wei (Thesis director) / Shi, Yixin (Committee member) / Fu, Lingchen (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The overall goal of this paper is to promote wellness, exercise and positive mental health. To encourage this goal, insight on the benefits of worksite wellness programs will be provided. Current worksite wellness programs focus minimally on the mental health benefits of exercise. Instead they focus on physiological results that come with worksite wellness programs. Exercise can provide both physiological and psychological health benefits (Ramirez & Wipfli, 2012). There should be more emphasis on mental health benefits of worksite wellness programs to provide positive mental health benefits in the workplace.
There are many different types of worksite wellness programs such as group fitness, on-site facilities and health allowances. It is important to vary wellness activities due to individuals having different fitness and health motivation. This implementation can become costly and require resources and support that many companies do not want to provide without successful results. Focusing on the psychological health benefits to such programs will allow companies to recognize the increase in productivity and positive work environment that result in worksite wellness programs. This will allow not only employees to benefit from the implementation of such programs but also the succession of the company.
This paper will explore ways to seek future enhancements within worksite wellness programs. Individuals will be given ways to positively contribute to work environments while maintaining healthy lifestyles. Companies will also better understand the importance that top recruits in the industry see within these types of programs. Through worksite wellness programs, employees will be provided with the tools necessary to improve their physical and mental health, while companies will have a more positive work environment as a result.
There are many different types of worksite wellness programs such as group fitness, on-site facilities and health allowances. It is important to vary wellness activities due to individuals having different fitness and health motivation. This implementation can become costly and require resources and support that many companies do not want to provide without successful results. Focusing on the psychological health benefits to such programs will allow companies to recognize the increase in productivity and positive work environment that result in worksite wellness programs. This will allow not only employees to benefit from the implementation of such programs but also the succession of the company.
This paper will explore ways to seek future enhancements within worksite wellness programs. Individuals will be given ways to positively contribute to work environments while maintaining healthy lifestyles. Companies will also better understand the importance that top recruits in the industry see within these types of programs. Through worksite wellness programs, employees will be provided with the tools necessary to improve their physical and mental health, while companies will have a more positive work environment as a result.
ContributorsJohnson, Sydney Rae (Author) / Hoffner, Kristin (Thesis director) / Marsit, Joseph (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Bexarotene is a synthetic analog of 9-cis-retinoic acid and ligand for the retinoid X receptor which has a history of clinical success in the treatment of T-cell lymphoma. Bexarotene has also shown potential for treating a variety of other cancers, which we seek to explore in this project. The potential of bexarotene lies in its unique mechanisms and wide application, however, it has shown limited effectiveness thus far in the treatment of breast and lung cancer, with moderate levels of efficacy and symptoms such as cutaneous toxicity, hyperlipidemia, and hypothyroidism. For this project several analogs of bexarotene were synthesized with the intentions of making a more potent ligand that can be used to treat these carcinomas while minimizing harmful side effects. We were successful in synthesizing a large variety of analogs over the span of roughly two years, including iso-chroman derivatives of bexarotene and NEt-TMN, in addition to a new series of analogs of the reported NEt-TMN derivative. These analogs were analyzed via melting point determination and nuclear magnetic resonance (NMR) spectroscopy to confirm the molecular structure and determine purity, and it is our intent to continue with further testing of these compounds to determine their effectiveness as well as the side effects they are likely to cause with levels of toxicity. Recent studies suggest that continuing the analysis of these compounds and other rexinoids like the ones described herein is a worthwhile endeavor as similar rexinoids have shown in numerous assays to be more potent and less toxic in the treatment of cancers when compared with bexarotene.
ContributorsMoen, Grant Anthony (Author) / Wagner, Carl (Thesis director) / Deutch, Charles (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05