Matching Items (120)
Description
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) that emerged from a zoonotic host at the end of 2019 and caused a public health crisis. In this collection of studies, Nicotiana benthamiana plants are used to set the foundation for producing monoclonal antibodies (mAbs) with homogeneous glycosylation to neutralize SARS-CoV-2 and potentially address the immunopathology often observed with severe COVID-19. Specifically, a mAb against the human interleukin (IL)-6 receptor (sarilumab) was generated and evaluated in vitro for its potential to reduce IL-6 signaling that has been shown to be associated with more severe cases of COVID-19. Furthermore, multiple mAbs that bind to the receptor-binding domain (RBD) of SARS-CoV-2 and efficiently neutralize the virus were developed using plant-based expression. Several of these mAbs are from different classes of RBD-binding mAbs that have distinct binding sites from one another. Several mAbs from different classes showed synergy in neutralizing the ancestral strain of SARS-CoV-2 and a smaller subset showed synergy when tested against the highly mutated Omicron (B.1.1.529) variant. Of interest, a novel RBD-binding mAb, termed 11D7, that was raised against the ancestral strain and derived from a hybridoma, appears to have an epitope on the RBD that contributes more synergy to a mAb combination that efficiently neutralizes the B.1.1.529 variant of SARS-CoV-2. This epitope was partially mapped by competitive binding and shows that it overlaps with another known antibody that binds a cryptic, distal epitope, away from the receptor binding site, giving insight into the potential mechanism by which 11D7 neutralizes SARS-CoV-2, as well as potentially allowing it to resist SARS-CoV-2 immune evasion more efficiently. Furthermore, this mAb carries a highly homogeneous glycan pattern when expressed in N. benthamiana, that may contribute to enhanced effector function and provides a tool to elucidate the precise role of crystallizable fragment (Fc)-mediated protection in SARS-CoV-2 infection. Ultimately, these studies provide evidence of the utility of plant-made mAbs to be used as cocktail members, giving clarity to the use of less potent mAbs as valuable cocktail components which will spur further investigations into how mAbs with unique epitopes work together to efficiently neutralize SARS-CoV-2.
ContributorsJugler, Collin (Author) / Chen, Qiang (Thesis advisor) / Lake, Douglas (Committee member) / Steele, Kelly (Committee member) / Mason, Hugh (Committee member) / Arizona State University (Publisher)
Created2022
Description
Weight stigma is a prevalent issue that has detrimental effects on health for both adolescents and parents. Adolescents are in a formative stage of life, so it is important to understand how parents may impact adolescents’ own experience with weight stigma. Past research has examined adolescent coping, body image, and associated stigma in the context of the parent-child relationship. This cross-sectional study examined self-reported weight stigma experience and internalization within 42 parent/adolescent dyads to provide greater understanding of how adolescents and parents are experiencing and internalizing weight stigma independently and transversely.
ContributorsMillett, Emma (Author) / McEntee, Mindy (Thesis director) / Adams, Marc (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2022-12
Description
Scientists are entrusted with developing novel molecular strategies for effective prophylactic and therapeutic interventions. Antivirals are indispensable tools that can be targeted at viral domains directly or at cellular domains indirectly to obstruct viral infections and reduce pathogenicity. Despite their transformative potential in healthcare, to date, antivirals have been clinically approved to treat only 10 out of the greater than 200 known pathogenic human viruses. Additionally, as obligate intracellular parasites, many virus functions are intimately coupled with host cellular processes. As such, the development of a clinically relevant antiviral is challenged by the limited number of clear targets per virus and necessitates an extensive insight into these molecular processes. Compounding this challenge, many viral pathogens have evolved to evade effective antivirals. Therefore, a means to develop virus- or strain-specific antivirals without detailed insight into each idiosyncratic biochemical mechanism may aid in the development of antivirals against a larger swath of pathogens. Such an approach will tremendously benefit from having the specific molecular recognition of viral species as the lowest barrier. Here, I modify a nanobody (anti-green fluorescent protein) that specifically recognizes non-essential epitopes (glycoprotein M-pHluorin chimera) presented on the extra virion surface of a virus (Pseudorabies virus strain 486). The nanobody switches from having no inhibitory properties (tested up to 50 μM) to ∼3 nM IC50 in in vitro infectivity assays using porcine kidney (PK15) cells. The nanobody modifications use highly reliable bioconjugation to a three-dimensional wireframe deoxyribonucleic acid (DNA) origami scaffold. Mechanistic studies suggest that inhibition is mediated by the DNA origami scaffold bound to the virus particle, which obstructs the internalization of the viruses into cells, and that inhibition is enhanced by avidity resulting from multivalent virus and scaffold interactions. The assembled nanostructures demonstrate negligible cytotoxicity (<10 nM) and sufficient stability, further supporting their therapeutic potential. If translatable to other viral species and epitopes, this approach may open a new strategy that leverages existing infrastructures – monoclonal antibody development, phage display, and in vitro evolution - for rapidly developing novel antivirals in vivo.
ContributorsPradhan, Swechchha (Author) / Hariadi, Rizal (Thesis advisor) / Hogue, Ian (Committee member) / Varsani, Arvind (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2022
Description
Heart disease is the leading cause of death in the developed world and often occurs following myocardial infarction. Apelin is an endogenous prepropeptide that has been studied for its role in improving cardiac contractility and vasodilation but suffers from a short half-life in the body. By encasing apelin in a nanoparticle patch, we were able to slowly release apelin to cardiac tissue and observe its effects for one month following induced myocardial infarction surgery in mice. This study demonstrates that the apelin nanoparticles can protect the heart from myocardial-induced heart failure, observing overall improved cardiac function and reduction of fibrotic scarring associated with post-myocardial infarction compared to a nontreated group.
ContributorsHenderson, Adam (Author) / Chen, Qiang (Thesis director) / Zhu, Wuqiang (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2022-05
Description
Weight stigma is present in many aspects of society, and especially in medicine. Weight stigma has detrimental effects on individuals physical and mental health, as well as patient-physician interactions. Application of weight-neutral healthcare ideologies such as Health at Every Size (HAES) are promising ways of decreasing weight stigma within the medical field without reducing the focus on improving patient health. Most widely applicable interventions include changing the focus of interactions from weight to health-promoting behaviors and lab values, improving provider education, and improving the general population's awareness of the problem.
ContributorsBrouhard, Mya (Author) / Chen, Qiang (Thesis director) / Parker, Lynn (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)
Created2024-05
Description
Platelet Rich Plasma (PRP) is an emerging procedure in regenerative medicine that offers a non-surgical minimally invasive way for tissue repair and regeneration. PRP has many different bioactive molecules that are able to influence and help achieve greater recovery and regenerative outcomes. Diet has many effects on platelets and looking at the mechanism in which platelet function and aggregation are affected with different diets shows how they are able to affect PRP therapy. Looking at these mechanisms allows for better physician recommendations for preprocedural diets to optimize efficacy. This paper conducts a systematic review to investigate the influence that diet can have on PRP outcomes. It was shown that high fat diets lower the efficacy of treatment while the Mediterranean diet helps promote platelet function and help efficacy. The future is to look at more diets while also integrating lifestyle choice before treatment for optimal outcomes.
ContributorsLaguna, Sebastian (Author) / Chen, Qiang (Thesis director) / Goyle, Ashu (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor)
Created2024-05
The Association Between Time to Eat and Students Fruit & Vegetable Consumption, Selection, and Waste
Description
Background: Studies have examined student fruit/vegetable (FV) consumption, selection, and waste related to lunch duration and found that longer duration at lunch was associated with greater consumption, selection, and reduced waste. However, few studies have investigated the relationship between time to eat and FVs. The aim of this research is to analyze the relationship between objective time to students took to eat (“time to eat”) as it relates to their fruit and vegetable consumption, selection, and plate waste.in elementary, middle, and high schools. Methods: A secondary analysis of cross-sectional study of 37 Arizona schools to discover the differences in the selection, consumption, and waste of FVs from students (Full N = 2226, Elementary N = 630, Middle School N = 699, High School N = 897) using objective time to eat measures. Zero-inflated negative binomial regressions examined differences in FV grams selected, consumed, and wasted adjusted for sociodemographics including race, ethnicity, eligibility for free or reduced lunch, academic year, and sex and clustering for students within schools. Results are presented across school level (elementary, middle, and high school).
Results: The average time taken to eat ranged from 10-12 minutes for all students. The association of time to eat and lunch duration were not closely related (r=0.03, p = 0.172). In the count model for every additional minute spent, there was a 0.5% greater likelihood of selecting FVs for elementary kids among those who took any FVs. In the zero-inflated model, it was found that there was a statistically significant relationship between time spent eating and the selection of fruits and vegetables. For the total sample and high schoolers, a minute more of eating time was associated with a 4.3% and 8.8% greater odds of selecting FV. This means that longer eating time increased the likelihood of choosing fruits and vegetables. The results indicated that the longer students took to eat, the higher the likelihood of consuming more of FVs. Each 10 more minutes spent eating (i.e., time to eat) is associated with a 5% increase in grams of FV selected relative to mean (for those that chose FV) over 1 week this equates to 32 g increase of FV selected. However, for middle schoolers, the time to eat was not found to be significant in relation to the grams of fruits and vegetables consumed. There was some significance in the sociodemographic factors such as gender (all) and other (middle school). There was a relationship between time taken to eat and waste as a proportion for fruits and vegetables. For example, among those among the students who wasted something (as a proportion of selection), each additional 10 minutes of eating time was associated with a .6% decrease in waste relative to the mean (for those who chose fruits and vegetables) over a week, resulting in a decrease in waste percentage of 16.5%. Among high schoolers, males had a slightly higher odds of wasting a proportion of fruits and vegetables.
Conclusions: This study aimed to examine the association between the time students take to eat during lunch and their fruit and vegetable (FV) consumption, selection, and plate waste. The findings revealed that the time to eat was related to FV consumption, depending on the school level. However, it was not significantly associated with FV selection or waste. The study emphasized the need for further research on time to eat, distinguishing it from the duration of lunch. Longer lunch periods and adequate time could influence better food choices, increased FV consumption, and reduced waste. The study highlighted the importance of interventions and school policies promoting healthier food choices and providing sufficient time for students to eat. Future research should validate these findings and explore the impact of socialization opportunities on promoting healthier eating habits. Understanding the relationship between lunch duration, time to eat, and students' dietary behaviors can contribute to improved health outcomes and inform effective strategies in school settings.
ContributorsDandridge, Christina Marie (Author) / Adams, Marc (Thesis advisor) / Whisner, Corrie (Committee member) / Bruening, Meg (Committee member) / Arizona State University (Publisher)
Created2023
Description
Coccidioidomycosis, or valley fever (VF), is a fungal infection caused by Coccidioides that is highly endemic in southern Arizona and central California. The antibody response to infection in combination with clinical presentation and radiographic findings are often used to diagnose disease, as a highly sensitive and specific antigen-based assay has yet to be developed and commercialized. In this dissertation, a panel of monoclonal antibodies (mAbs) was generated in an attempt to identify circulating antigen in VF-positive patients. Despite utilizing a mixture of antigens, almost all mAbs obtained were against chitinase 1 (CTS1), a protein previously identified as a main component in serodiagnostic reagents. While CTS1 was undoubtedly a dominant seroreactive antigen, it was not successfully detected in circulation in patient samples prompting a shift toward further understanding the importance of CTS1 in antibody-based diagnostic assays. Interestingly, depletion of this antigen from diagnostic antigen preparations resulted in complete loss of patient IgG reactivity by immunodiffusion. This finding encouraged the development of a rapid, 10-minute point-of-care test in lateral flow assay (LFA) format to exclusively detect anti-CTS1 antibodies from human and non-human animal patients with coccidioidal infection. A CTS1 LFA was developed that demonstrated 92.9% sensitivity and 97.7% specificity when compared to current quantitative serologic assays (complement fixation and immunodiffusion). A commercially available LFA that utilizes a proprietary mixture of antigens was shown to be less sensitive (64.3%) and less specific (79.1%). This result provides evidence that a single antigen can be used to detect antibodies consistently and accurately from patients with VF. The LFA presented here shows promise as a helpful tool to rule-in or rule-out a diagnosis of VF such that patients may avoid unnecessary antibacterial treatments, improving healthcare efficiency.
ContributorsGrill, Francisca J (Author) / Lake, Douglas F (Thesis advisor) / Magee, D Mitch (Committee member) / Grys, Thomas (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2023
Description
Tools designed to help match people with behaviors they identify as likely to lead to a successful behavioral outcome remain under-researched. This study assessed the effect of a participant-driven behavior-matching intervention on 1) the adoption of a new behavior related to fruit and vegetable (F&V) consumption, 2) study attrition, and 3) changes in F&V consumption. In this two-arm randomized controlled trial, 64 adults who did not meet standard F&V recommendations were allocated to an intervention (n=33) or control group (n=31). Participants in the intervention group ranked 20 F&V-related behaviors according to their perceived likelihood of engagement in the behavior and their perception of the behavior’s efficacy in increasing F&V consumption. Participants in the intervention group were subsequently shown the list of 20 behaviors in order of their provided rankings, with the highest-ranked behaviors at the top, and were asked to choose a behavior they would like to perform daily for 4 weeks. The control group chose from a random-order list of the same 20 behaviors to adopt daily for 4 weeks. During the study period, text messages were sent to all participants 90 minutes before their reported bedtime to collect Yes/No data reflecting successful behavior engagement each day. The binary repeated-measures data collected from the text messages was analyzed using mixed-effects logistic regression, differences in attrition were assessed using log-rank analysis, and change scores in F&V consumption were compared between the two groups using the Man-Whitney U test. P<0.05 indicated significance. The rate of successful behavior adoption did not differ significantly between the two groups (b=0.09, 95%CI= -0.81, 0.98, p=0.85). The log rank test results indicated that there was no significant difference in attrition between the two groups (χ2=2.68, df=1, p=0.10). F&V consumption increased significantly over the 4 weeks in the total sample (Z=-5.86, p<0.001), but no differences in F&V change scores were identified between the control and intervention groups (Z=-0.21, p=0.84). The behavior-matching tool assessed in this study did not significantly improve behavior adoption, study attrition, or F&V intake over 4 weeks.
ContributorsCosgrove, Kelly Sarah (Author) / Wharton, Christopher (Thesis advisor) / Adams, Marc (Committee member) / DesRoches, Tyler (Committee member) / Grebitus, Carola (Committee member) / Johnston, Carol (Committee member) / Arizona State University (Publisher)
Created2023
Description
Objective: It’s not well understood how youth perceive existing fruit and vegetable (FV) marketing materials available in schools. This ancillary study sought to assess the acceptability of FV marketing materials freely available to schools among adolescents in grades 6-12.
Methods: Middle and high school adolescents (n=40; 50% female; 52.5% Hispanic) in the Phoenix, AZ area were asked to rank marketing materials (n=35) from favorite to least favorite in four categories: table tents, medium posters, large posters and announcements. Favorites were determined by showing participants two items at a time and having them choose which they preferred; items were displayed to each adolescent in a random order. Adolescents participated in a 20-30 minute interview on their favorite items in each category based on acceptance/attractiveness, comprehension, relevance, motivation and uniqueness of the materials. A content analysis was performed on top rated marketing materials. Top rated marketing materials were determined by the number of times the advertisement was ranked first in its category.
Results: An analysis of the design features of the items indicated that most participants (84%) preferred marketing materials with more than 4 color groups. Participant preference of advertisement length and word count was varied. A total of 5 themes and 20 subthemes emerged when participants discussed their favorite FV advertisements. Themes included: likes (e.g., colors, length, FV shown), dislikes (e.g., length, FV shown), health information (e.g., vitamin shown), comprehension (e.g., doesn’t recognize FV), and social aspects (e.g., peer opinion). Peer opinion often influenced participant opinion on marketing materials. Participants often said peers wouldn’t like the advertisements shown: “…kids my age think that vegetables are not good, and they like food more than vegetables.” Fruits and vegetable pictured as well as the information in the marketing materials also influenced adolescent preference.
Conclusion: Students preferred advertisements with more color and strong visual aspects. Word count had minimal influence on their opinions of the marketing materials, while information mentioned and peer opinion did have a positive effect. Further research needs to be done to determine if there is a link between adolescent preferences on FV marketing materials and FV consumption habits.
Methods: Middle and high school adolescents (n=40; 50% female; 52.5% Hispanic) in the Phoenix, AZ area were asked to rank marketing materials (n=35) from favorite to least favorite in four categories: table tents, medium posters, large posters and announcements. Favorites were determined by showing participants two items at a time and having them choose which they preferred; items were displayed to each adolescent in a random order. Adolescents participated in a 20-30 minute interview on their favorite items in each category based on acceptance/attractiveness, comprehension, relevance, motivation and uniqueness of the materials. A content analysis was performed on top rated marketing materials. Top rated marketing materials were determined by the number of times the advertisement was ranked first in its category.
Results: An analysis of the design features of the items indicated that most participants (84%) preferred marketing materials with more than 4 color groups. Participant preference of advertisement length and word count was varied. A total of 5 themes and 20 subthemes emerged when participants discussed their favorite FV advertisements. Themes included: likes (e.g., colors, length, FV shown), dislikes (e.g., length, FV shown), health information (e.g., vitamin shown), comprehension (e.g., doesn’t recognize FV), and social aspects (e.g., peer opinion). Peer opinion often influenced participant opinion on marketing materials. Participants often said peers wouldn’t like the advertisements shown: “…kids my age think that vegetables are not good, and they like food more than vegetables.” Fruits and vegetable pictured as well as the information in the marketing materials also influenced adolescent preference.
Conclusion: Students preferred advertisements with more color and strong visual aspects. Word count had minimal influence on their opinions of the marketing materials, while information mentioned and peer opinion did have a positive effect. Further research needs to be done to determine if there is a link between adolescent preferences on FV marketing materials and FV consumption habits.
ContributorsPisano, Sydney Alexis (Author) / Bruening, Meg (Thesis advisor) / Adams, Marc (Committee member) / Grgich, Traci (Committee member) / Arizona State University (Publisher)
Created2019