There is a growing attention in the synthesis of fructo-oligosaccharides (FOS) due to their excellent bio-functional and health-promoting properties. The current production processes are limited to chemical hydrolysis reactions of plant extracts, which are often associated with several drawbacks. In this study, fructosyltransferase (FTase) and polygalacturonase (PGase) activities, present in a commercial enzyme preparation (Pectinex® Ultra SP-L) sourced from Aspergillus aculeatus, have been separated and fully purified by anion-exchange and sizeexclusion chromatography. The FTase possesses fructosyl transfer activity for FOS synthesis and the PGase has pectin hydrolytic activity. Fructosyltransferase is a single-band protein with a molecular weight of 85 kDa, whereas PGase is a distinct protein of 40 kDa. The temperature and pH optima of FTase were 60 ºC and 6.0, with a half-life of 8 h; while that for PGase were 40 ºC and 6.0, respectively. FTase was slightly inhibited in the presence of Ni²⁺, Mg²⁺ and urea; but PGase was more susceptible to divalent ions such as Ca²⁺, Mg²⁺ and Mn²⁺. The kinetic parameters (Km and Vmax) of FTase for the hydrolysis of β-(2→1) linkages from sucrose were 752.3 mM and 120.5 μmol.min⁻¹.mL⁻¹, respectively; whereas the same parameters for pectin hydrolysis by PGase were 13.0 mg.mL⁻¹ and 263 μmol.min-1.mL⁻¹, respectively. The purified FTase was able to transfer fructosyl residues from sucrose, synthesizing the corresponding chains of FOS. PGase was relatively stable at 40 ºC (t½ > 3 h), depolymerizing the pectin backbone while releasing the inulins from within the chicory roots. Analysis of various mixtures of FOS by mass spectrometry, HPLC and ¹H-NMR was undertaken. Results indicated that MS with electrospray ionization and ¹H-NMR are capable of providing relative quantitative data of the FOS present in the mixtures. The pharmaceutical effects of various sc-FOS (0.5%, v/v) and SCFA (0.3%, v/v) on certain bacterial enzymes (β-glucuronidase, urease and β-glucosidase) associated with the formation of carcinogens were also studied. These enzyme activities were not directly influenced by the sc-FOS, but were found to be remarkably decreased by SCFA, pointing toward the prebiotic effect of FOS in intestinal microflora modulation.

A culturally-based theoretical model about how cultural beliefs about cancer and breast cancer screening techniques influence the screening behaviors of women of Mexican descent was developed using grounded theory. Across levels of acculturation and socioeconomic status, 34 women (49 to 81 years old) were interviewed through focus groups. Women who hold more traditional health beliefs about causes, nature, and responsibility with regard to breast cancer are more likely to "feel healthy" and not engage in breast cancer screening. Women who hold more traditional beliefs about propriety of female and health care provider behavior are more likely to "feel indecent" and also not engage in screening. The cultural health belief model is integrated within a sociocultural and a socioeconomic context.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) prevention, screening, and treatment strategies. With CRC incidence on the rise in younger populations, there is an increased need to engineer technologies that enhance patient access to diagnostic exams and disease management. This dissertation presents the development of an orally-delivered probiotic to screen for and treat early CRC lesions with a particular emphasis on translatability factors including: safety of probiotic use, exploration of oral delivery, and testing in clinically relevant models. At the interface of immunology, synthetic biology, and the microbiome fields is the overarching concept that microbes play a critical role in the tumor microenvironment (TME). The innate ability of bacteria to seek out tumor-specific signatures and proliferate within their necrotic cores due to reduced immune surveillance enables the precise immunoengineering of the local TME. Here, we will design, characterize, and test a probiotic encoded with a lysis mechanism to aid in biocontainment and maximize the release of recombinantly-produced diagnostic and immunotherapeutic cargo. In this lysis circuit, bacteria grow to a critical density within tumors and synchronously lyse, locally releasing their payload. A small fraction of bacteria remains to reseed the population and the cycle continues, resulting in repeated and sustained drug delivery. Drawing from advancements in immunology, we engineered bacteria to produce immune checkpoint inhibitors. Monoclonal antibodies targeting immune checkpoints have revolutionized cancer therapy, but only work in a subset of patients and can lead to a multitude of toxicities, suggesting the need for more targeted delivery systems. Due to their preferential colonization of tumors, bacteria are a natural chassis for the localized delivery of such therapeutics. Therefore, we engineered a commercially available probiotic, E.coli Nissle 1917 (EcN), for the controlled production and intratumoral release of nanobodies targeting programmed cell death protein – ligand 1 (PD-L1) and cytotoxic T- lymphocyte-associated protein-4 (CTLA-4) using the described lysing release mechanism. We demonstrate that a single injection of this engineered probiotic enhanced therapeutic response compared to analogous clinically-relevant antibodies, resulting in tumor regression in syngeneic mouse models. In an effort to create a more effective therapeutic for poorly immunogenic cancers, we utilized the modularity of our platform to slow tumor growth in mouse models of established CRC by combining it with a probiotically-produced cytokine, granulocyte-macrophage colony stimulating factor (GM-CSF). We sought to expand upon the relevance of this approach for early-stage CRC screening and treatment, by characterizing the platform in CRC precancerous lesions, or adenomas. When orally-delivered, EcN robustly colonized adenomas in genetically-engineered and orthotopic murine models of CRC, and human CRC patients. Leveraging adenoma-specific colonization, we probed for EcN presence in fecal matter, demonstrating its utility as a non-invasive screen for adenomas. For more accessible testing, we engineered EcN to produce salicylate and showed that it could be detected in the urine of tumor-bearing mice for days after oral delivery of the probiotic. Moreover, we demonstrated that the therapeutic effectiveness of our previously engineered therapeutic strain, producing PD-L1, CTLA-4 and GM-CSF, was maintained when delivered orally, ultimately resulting in significant adenoma reduction. Altogether, this dissertation aims to highlight the potential for engineered EcN to be used as a safe, orally-deliverable screening and therapeutic platform for early-stage CRC disease. While we have chosen to focus on CRC here, we will conclude by discussing efforts to adapt this platform to work in combination with other cellular therapies and therapeutic indications, ultimately engineering a platform to impact a broader patient population.

Indoor tanning (IT) increases risk of developing skin cancer. A social media campaign to reduce mother's permissiveness toward their teenage daughters IT was evaluated. Mothers (N = 869) of daughters aged 14–17 in 34 states without bans on IT by minors were enrolled in a randomized trial with assessments at baseline and 12-months follow-up in 2017–19. A year-long adolescent health campaign was delivered to all mothers. The intervention group received posts on preventing IT and the control group, posts about preventing prescription drug misuse. Daughters (n = 469; 54.0%) completed the assessments at baseline and 12 months. At 12-month follow-up, intervention-group mothers were less permissive of IT by daughters (unadjusted means = 1.70 [95% CI: 1.59, 1.80] v. 1.85 [1.73, 1.97] [5-point Likert scale], b = -0.152), reported more communication about avoiding IT with daughters (4.09 [3.84, 4.35] v. 3.42 [3.16, 3.68] [sum of 7 yes/no items], b = 0.213), and had lower intentions to indoor tan (1.41 [1.28, 1.55] v. 1.60 [1.43, 1.76] [7-point likelihood scale], b = -0.221) than control-group mothers. Daughters confirmed intervention-group mothers communicated about IT (3.81 [3.49, 4.14] v. 3.20 [2.87, 3.53] [sum of 7 yes/no items], b = 0.237) and shared IT posts (unadjusted percentages = 52.4% v. 36.4%, b = 0.438) more than control-group mothers. No differences were found in IT behavior, self-efficacy to refuse permission, and negative attitudes toward IT. A social media campaign may be an effective strategy to convince mothers to withhold permission for IT, which may help increase the effectiveness of state laws designed to reduce IT by minors by requiring parental permission.

The present study examined theoretical mediators of a parent-based intervention on sunbathing tendencies and sunburn frequencies based on the work of Turrisi et al. [Turrisi, R., Hillhouse, J., Heavin, S., Robinson, J., Adams, M., & Berry, J. (2004). Journal of Behavioral Medicine, 27, 393-412.]. Three hundred and forty parents in two regions of the United States were educated about the dangers of risky sun behavior and how to convey information about skin cancer prevention to their children. Attitudes toward sunbathing, health beliefs, appearance beliefs, and social normative beliefs were examined and found to be significant mediators of program effects on sunbathing tendencies and sunburn frequencies. The findings are discussed with respect to maximizing the effectiveness of future skin cancer interventions with children.

No description available.

The stage at diagnosis is the single most important predictor of lung cancer outcome. Therefore, detecting lung cancer early is of utmost importance. Low-dose computed tomography (LDCT) has proven beneficial in the early detection and mortality reduction of lung cancer. Despite this, very few of the high-risk population get annual LDCT done. Patients' attitudes towards tobacco usage and preventive care can be a factor in getting LDCT. We analyzed the relationship between the willingness to undergo LDCT and a person's readiness to try tobacco cessation medication or get the pneumococcal vaccine. We also analyzed the relationship between patients who had tobacco cessation counseling and their willingness to get LDCT and pneumococcal vaccine. Medical records of high-risk patients seen in the East Tennessee State University (ETSU) clinics between January 1, 2016, and November 30, 2020, were analyzed retrospectively. In the data obtained, a total of 2,834 patients were current smokers and were included in the research. The study subjects were assessed in two ways, which from here on will be referred to as method one and method two. In the first method, patients who underwent LDCT were assessed, and the outcome investigated was tobacco cessation counseling, tobacco cessation medication prescription, and pneumococcal vaccination. In the second method, patients who had tobacco cessation counseling were assessed, and the outcome evaluated was LDCT, tobacco cessation medication prescription, and pneumococcal vaccination. In the first method, out of 2,834 total population, 570 had undergone at least one LDCT screening during the study period. Of the 570 patients who underwent LDCT, 22.8% tried one of the tobacco cessation medications at least once during the study period (vs. 9.8% in patients who did not get the LDCT). Also, 71.5% of patients who had LDCT received at least one dose of pneumonia vaccine (vs. 35.5% in patients who did not get the LDCT). In the second method, 1,673 out of 2,834 patients received at least one tobacco cessation counseling, and out of those, 27.5% had LDCT screening (vs. 9.5% among those who never received counseling). Also, 54.9% received a pneumococcal vaccine (vs. 45.1% among those who did not receive counseling). The study demonstrates a relationship between getting LDCT and getting a pneumococcal vaccine or tobacco cessation medications. It also reveals that tobacco cessation counseling increases the odds of getting LDCT, tobacco cessation medications, and pneumococcal vaccine.

Breast cancer is the most common cancer type in the United Kingdom. Many women with breast cancer do not show any noticeable symptoms in their early stages, hence regular breast screening is important. In this research focus is on medical imaging and its role in breast cancer screening, diagnosis, and treatment monitoring. Around 10% of all cancers are caused by inherited gene mutations which may cause cancer to run in families. Though, majority of cancer cases (up to 90%) are caused by acquired gene mutations which may also appear to run in families when family members share a particular environment or exposure. Genetic testing is conducted in this research on a number of participants to investigate the cancer cases found among their families. The findings of this research show that significant improvements have taken place in the emergence of hybrid imaging modalities used for breast imaging, through the fusion of different imaging techniques. The findings also provide evidence that similar to cancers caused by inherited gene mutations, cancers caused by non-inherited gene mutations may also appear to run in families when family members share certain environments and exposures or lifestyle behaviours. As a result, a new genetic concept of cancer essential to understand and control the disease is presented in this work which links between the human population origins and migrations, environmental factors and gene mutations, and the development of cancer. Furthermore, a number of cancer prevention strategies are recommended in this study to prevent people from getting the disease.

No description available.

Food guides have been used for many years to aid individuals in food selection. This investigation was conducted in order to assess the compliance of college students with the National Cancer Institute's "Five A Day" recommendation. Three-day average consumption levels of antioxidants vitamin C, vitamin E, and beta carotene and the average number of servings of fruits and vegetables consumed were determined for 217 college students (95 males and 122 females) enrolled in an introductory nutrition class. Nutritional analysis was carried out using the Nutritionist IV software package. Descriptive statistics of the data included means and ranges. Results indicated that 82% of the students obtained 70% of the RDA for vitamin C and 85% obtained 70% of the RDA for vitamin E; 29% obtained 70% of the level of beta carotene recommended to reduce the risk of developing cancer. College students obtained adequate amounts of vitamin C but inadequate amounts of vitamin E and beta carotene recommended to reduce the risk of developing certain cancers. Males obtained higher levels of vitamin C and E, while females obtained a higher level of beta carotene. Thirty-four percent of the students consumed at least two servings of fruits daily and 26% consumed at least three servings of vegetables daily. A total of 26% of the students obtained the recommended five or more servings of fruits and vegetables. Males consumed a slightly greater number of fruits and vegetables compared to females. Consumption of at least five servings of fruits and vegetables, in any combination, provided levels of vitamin C and beta carotene recommended to reduce the risk of developing cancer (52) but a marginal level of vitamin E (contained primarily in foods other than fruits and vegetables). Because cancer is one of the most common causes of death in the United States and because its risk can be reduced by appropriate diet, produce consumption should be encouraged. The Five A Day program has been developed to do this. Unfortunately, this program has reached only a small sector of the public. Therefore, health practitioners as well as individuals involved in the food industry must concentrate their efforts in educating the public to make wise food choices. / Master of Science