Enhancing Early Detection of Alpha-Gal Syndrome in Rural Primary Care

D.N.P

FBF/PUF and CYB-1/Cyclin B Proteins Promote Sperm Viability by Inhibiting Apoptosis in C. elegans Germline

Using the nematode Caenorhabditis elegans as a model organism, I investigated the role of FBF (Fem-3-Binding Factor) and CYB-1 (one of three B-type Cyclins) proteins in the survival of sperm cells. FBF proteins (FBF-1 and FBF-2) play a role in the maintenance of germline stem cells, while CYB-1 regulates the cell cycle. Previous research revealed in the fbf-1 fbf-2 double mutant, only sperm cells are present with no oocytes or germline stem cells. In this study, it is hypothesized that both FBFs and CYB-1 proteins are required for sperm cell maintenance by repressing apoptosis mediated by CED-4 and/or MPK-1. CED-4 is a pro-apoptotic protein that initiates apoptosis, and MPK-1 plays a role in germ cell apoptosis. To test this hypothesis, I employed two triple mutant strains – fbf-1 fbf-2; ced-4 and fbf-1 fbf-2; mpk-1. Specifically, I performed cyb-1 RNAi in these mutants from L1 stages and counted the number of sperm at 20 °C after staining dissected gonads with anti-MSP (sperm cell marker). I found that cyb-1 RNAi eliminated sperm cells in the fbf-1 fbf-2; mpk-1, but not in the fbf-1 fbf-2; ced-4 mutant germlines. These results indicate that FBFs and CYB-1 proteins protect sperm cells by inhibiting CED-4-mediated apoptosis in the C. elegans germline. Importantly, these regulators are also highly expressed in the reproductive systems of other organisms, including humans. Therefore, these findings and future work may provide insight into germ cell maintenance in humans and other organisms

SYNTHESIS AND ANALYSIS OF PYRENE-CONTAINING LISINOPRIL ANALOGS TO STUDY ACE INHIBITION

Cardiovascular disease (CVD) is a leading cause of death worldwide. One of the major risk factors in developing CVD is hypertension, characterized by extended periods of increased blood pressure. Blood pressure is managed by the renin-angiotensin-aldosterone system (RAAS), of which angiotensin converting enzyme (ACE) is a key player. Lisinopril, one of the most prescribed medications in the world, is an ACE inhibitor with common side effects that can limit its use. The aim of this work is to prepare a small library of fluorescent, lisinopril-like compounds whose interaction with the ACE active site can be directly measured using fluorescence spectroscopy. Testing of such compounds is expected to shed light on the enzyme’s ability to accommodate much larger hydrophobic groups than are found in lisinopril, and to determine if the carboxylate units in the native drug are essential for binding, perhaps paving the way for future inhibitor development. Thus, several new pyrene-containing analogs were prepared using automated peptide protocols. In the presence of ACE, the putative inhibitors showed small increases in fluorescence intensity, suggesting they can enter the enzyme active site. The analogs were then challenged to inhibit ACE hydrolysis of an angiotensin I peptide containing a different (non-pyrene) fluorophore. The amidation state of the C-terminus of the lisinopril analogs appears to be a considerable factor in their ability to influence the rate of ACE hydrolysis, though additional studies are warranted

The Role of Response Regulators in Gram-Negative Bacterial Resistance

Since their beginning, antibiotics have been hailed as a miracle of modern medicine. And while their discovery brought about exciting advances across a multitude of industries, the ubiquity of their use has paved the path leading towards the current resistance crisis and the dawn of a post-antibiotic era. As resistant bacteria have emerged steadily over time, updated methods of treating infections have developed. From double treatments using two antibiotics or recycling older antibiotics, these changes have come about in hopes to delay resistance and prolong the lifespan of the antibiotics currently in use. Included in the older classes of antibiotics is polymyxins, their usage gone to wayside due to their innate nephro and neuro-toxic characteristics. The use of polymyxins has now been reconsidered to overcome highly resistant pathogens typically found in healthcare settings. And while the side effects of polymyxin treatment can be deleterious it is a more preferable outcome than succumbing to a fatal infection. Nosocomial infection have become more and more prevalent, threatening patients within ICUs and under long term care. Some of the major contributors of the most concerning nosocomial infections are the E.S.K.A.P.E. pathogens, these are (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Named for their ability to escape treatment, they are notorious for causing dangerous infections and rapidly developing resistance characteristics. Globally recognized institutions such as the World Health Organization have declared a state of emergency and have issued a call to action to academic institutions, pharmaceutical developers, and government agencies to come together to prevent the reality of a world overrun with untreatable infections. In response, there has been extensive work done to understand the variety and nuance of resistance mechanisms. Additionally, strides have been made towards newer methods of ameliorating resistance through the use of small molecule antibiotic adjuvants. Adjuvants work in tandem with drugs to improve their efficacy. The following body of work explores the mechanisms and application of two such adjuvants, 2-aminoimidazole compounds and several salicylanilide kinase inhibitors. Both of these compounds target separate components of systems found in most bacteria and are responsible for regulating the expression of resistance inducing genes. Two-component systems (TCSs) are present in most bacteria, playing a crucial role in how they sense and respond to environmental signals. TCSs have been an attractive drug target since their roles in a wide variety of cellular processes, such as nutrient uptake, motility and virulence, have been elucidated. Conveniently they appear to have no mammalian homolog, making then an ideal candidate for intervention. As their name would suggest, TCSs have two distinct components, a membrane-bound sensor kinase and a response regulator that is responsible for directly binding DNA and altering expression levels. Working as a unit, the histidine kinase responds to environmental signals by autophosphorylating and transferring the phosphoryl group to the response regulator to activate its regulatory function. While not every TCS works in this way, this is a typical example and is the most common mechanism. The TCS responsible for polymyxin resistance in species such as K. pneumoniae, A. baumannii, E. coli and numerous others is the PmrAB system. The histidine kinase, PmrB, and its cognate response regulator, PmrA, have been implicated as the mechanism responsible for inducing changes to the outer membrane of the aforementioned bacteria, these changes alter the normal charge of the outer membrane. Polymyxins are cationic and in susceptible populations of bacteria have an affinity for the negatively charged outer membrane. However, due to the PmrAB system resistant strains are able to decorate lipid-A molecules located on the outer membrane with functional groups that change the charge of the membrane as whole. The cross talk between these two molecules is subtle but complex. We have found through investigations of point mutations in highly resistant strains of A. baumannii that a single amino acid substitution can alter this signaling cascade in profound ways to increase the bacteria’s ability to survive treatments. These alterations were shown to affect PmrA’s ability to accept the phosphoryl group from PmrB in one of two ways, either by altering regions necessary for kinase recognition or perturbing the binding pocket. And while we originally hypothesized the point mutations would exert a noticeable effect of DNA-binding affinity we found that the mutants were slower to activate, lessening the energy exerted by the cell and prolonging the lifetime of the activation signal. The goal of developing small molecule adjuvants to target the PmrAB system is to interrupt the system on both sides. IMD-0354 has shown an ability to bind and inhibit the proper functioning of sensor kinase, PmrB, while 2-aminoimidazole compounds bind and inhibit the response regulator in a similar fashion. Both compounds have a minimum inhibitory concentration (MIC) lowering effect, however because polymyxins are highly toxic our goal evolved into bringing down the necessary concentration of polymyxin even lower. We performed minimum inhibitory concentration experiments to test if these two compounds can be used congruently with colistin to break the resistance mechanisms and make bacteria susceptible to treatment once again. Our endeavor was ultimately successful, bringing down the colistin MIC in resistant A. baumannii strain AB4106 to 10 µg/mL and under, a 200-fold decrease. Our goal is to apply this method to other TCSs and displace other organisms from their status as resistant pathogens

Empowering Behavior Change in Adults with Diabetes Through Nutrition Education and Motivational Interviewing

D.N.P

NECESSARY PRECONDITIONS FOR RE-IMAGINING CASE MANAGEMENT: CULTIVATING A SECURE MINDSET IN HIGH SCHOOL CASE MANAGERS

To combat the disproportionate outcomes of Black and Brown students who transfer to continuation schools, students need a case management system to support them to stay on track for graduation at a comprehensive high school. In this participatory action research (PAR) study, a group of co-practitioner researchers (CPR) and I examined how to address a change in the case management system. As a result, we learned that the staff who support our most vulnerable students need parallel support to be case managers and to re-imagine case management. Using CLE protocols for discussion and engagement and qualitative research methods to analyze iterative data from three cycles of inquiry over 14 months, we cultivated relational trust and participated in open discussions about student and staff needs. Two findings pointed us to the need to fully engage adults in dialogue and self-care before they can effectively change the case management system for the students in our school. First, adults who engage with students as case managers need supportive parallel spaces in which to build trust, reflect, and sustain their resilience and agency. Secondly, to re-imagine a case management system, staff need support to develop secure mindsets and fully commit to caring for students. The team identified compassion fatigue as a primary factor in staff inability to take on full responsibility or re-imaging a more effective case management system. This study brings attention to the compassion fatigue that staff experience and their need for supportive structures before they can make systemic changes. The findings have implications for educational leaders trying to guide teachers and staff in reform efforts; adult caregivers in schools need concurrent emotional support so they can support students. To collaborate, leaders must work to ensure the preconditions for effective change efforts -- secure mindsets and practice using tools and protocols that support them to engage in productive change processes

Evaluation of Patient Engagement on Driveline Infection Rates in LVAD Patients through Digital Education

Mechanical circulatory support in the form of a left ventricular assist device (LVAD) can support patients with advanced Heart Failure (HF). The most common complication following LVAD implantation is driveline infection (DLI) leading to increased morbidity, mortality, and costs. Management of the driveline insertion site by the patient at home after discharge is critical in prevention of DLI. A quality improvement project utilizing the FADE model was conducted by leveraging video-based education delivered via an electronic health portal and evaluated the impact on infection rates, 30-day readmission rates in LVAD patients, and patient engagement. Post-implementation, the DLI rates remained unchanged, 30-day readmission rates improved slightly, and patient engagement was low with newly implanted patients although higher in prior implants. Limitations included types of delivery mechanisms within the electronic health portal and overall engagement and activation of the electronic health portal. The use of video-based education allowed for consistent delivery of educational material and has the ability to impact morbidity, mortality, and costs. A multi-modal approach to LVAD education supports enhanced patient education and earlier engagement may be more beneficial to enhance utilization. Future recommendations include evaluation of timing of delivery and other delivery methodologies such as QR codes.D.N.P

ONE-SESSION MINDFULNESS MEDITATION AND ITS EFFECTS ON ACADEMIC STRESS

This study explores one-session mindfulness and its effects on academic stress. Studies mindfulness meditation practices look to improve mental health, reduce stress, and improve cognitive and emotional regulation across diverse populations. The purpose of this study was to find out if a singular session of mindfulness helped reduce academic stress in the present moment. Using guided audio recordings, the Sham Mindfulness group was presented with a generic meditation script while the Mindfulness Meditation group was presented the an in-depth mindfulness practice. They were then measured in the Mindfulness Attention Awareness Scale- State (MAAS-State), the Perceived Stress Scale (PSS), and the Perceived Academic Stress (PAS). Results indicated that there was a significant effect in reducing perceived stress, but not a significant effect in improving state mindfulness or reducing academic stress. These findings suggest that a singular session of mindfulness meditation practices can lower general stress. Regarding state mindfulness and academic stress, there needs to be further research done on the effects of one-session mindfulness

Does AI Pass the Smell Test? Evaluating Artificial Intelligence Applications in Rhinology Patient Education

Introduction: Rhinologic procedures and the management of rhinological conditions require a deep understanding of intricate anatomy and complex decision-making. To address the need for a patient learning tool and a resource to answer common rhinology-related questions, we explored the utility of ChatGPT, a state-of-the-art language model to assist in patient education on common rhinologic questions and procedures. We conducted a comprehensive evaluation of ChatGPT's responses, comparing them with a panel of expert reviewers and explored its potential applications in the field of rhinology. Methods: ChatGPT was utilized to generate responses to common questions related to rhinology and rhinologic procedures. Topics for evaluation included reasons for a stuffy nose, explaining chronic rhinosinusitis, applications and indications for sinus surgery, and post-surgical expectations and associated risks of sinus surgery. These responses were meticulously recorded and subsequently incorporated into a survey for evaluation. The survey was distributed to a panel of experienced rhinologists, who were tasked with evaluating the quality of responses. Evaluation criteria included an overall quality score of the responses, identifying errors or missing information if applicable, and recognizing any aberrant medical advice. Rhinologists were asked to assess the correspondence of ChatGPT's responses with their current medical standard. Results: We performed a systematic literature review to identify current use cases of artificial intelligence in rhinology. This review highlighted the evolving role of AI in diagnosing, treatment planning, radiographic interpretation, and post-operative monitoring in rhinological cases. AI-based tools have demonstrated promise in automating repetitive tasks, enhancing diagnostic accuracy, and aiding in surgical planning. Very few centered on the patients' experience or education so we sought to address this gap by evaluating publicly available tools to answer commonly asked questions from patients. To do this, a panel of experienced rhinologists evaluated ChatGPT's responses to provided prompts. The evaluation revealed that ChatGPT's responses varied in quality, with a mix of accurate information, minor errors, and occasionally suboptimal advice. While ChatGPT's responses demonstrated potential as an educational tool, they often lacked the depth of understanding and context that experienced rhinologists possess. Despite some pitfalls in the responses, rhinologists scored the responses on average 8.17 out of a maximum of 10. The responses were found to be valuable in addressing many common questions but less reliable in complex decision-making scenarios. Conclusion: ChatGPT offers a valuable resource for educating patients and providing quick answers to common rhinological inquiries. However, its limitations become evident when addressing intricate, multifaceted issues or complex medical decision-making. Further developments in AI, specifically tailored to rhinology, hold potential for improving patient education, diagnostics, and surgical planning in this specialized medical field. The integration of AI tools in rhinology has the potential to enhance patient care, but careful consideration of their limitations and the need for expert oversight is essential in their implementation

Dear Ivy

Have you ever wanted to get something more out of the love stories that you read? Something that remains in your body as your fingertips turn the final page and you just feel as though something is missing in a book’s very essence. You read tales of love and relationships but more often than not, they’re unrealistic and idealized versions of the strange emotion that we have all experienced throughout our lifetime. Our collection ties together many genres under the overarching theme of love that not only include happy, idealized relationships, but that also unveil the raw truth of how love can leave us. Sometimes family members pass away and that leaves a hole in your heart, sometimes the one you believed to be the love of your life is just another lesson, and sometimes you find that the friend you’ve known for ages has been your soulmate all along. Love exists in the real world, and our stories reflect the reality of what can happen to those who stumble into its enchantment. Written by two North Carolina college students, Dear Ivy, is a unique and diverse collection of short stories that explores love in all shapes, sizes, and forms. Within this book, you’ll find stories about everlasting love and “happily ever after”, while also finding stories about platonic love, friendship, familial relationships, and more. These tales are organized by the Victorian art of floriography, a practice in which flowers are like words, and every blossom has its own message to convey. Each story is titled after a special bloom with its unique meaning that goes on to provide the theme to the story with its namesake. As you read, you’ll constantly find the idea that love exists everywhere and within everyone and can be found in all facets of life as it does not discriminate between culture, ethnicity, gender identity, or sexual orientation. Love, as a concept, is realistic, enduring, poetic, and enchanting to many readers, and the twenty-two stories housed in this book encapsulate the concept that has inspired humanity for millennia. The only question that remains is this; would you like to fall into that world with us