Air pollution is a key component to understanding the Public Health of populations globally, with Diesel Exhaust Particles (DEP) being a significant contributor to traffic-related air pollution. Exposure to DEPs varies across populations and is therefore crucial to understanding the continual impacts of traffic-related air pollution on the public. Prior research has indicated that the formation of Amyloid-𝛽 (A-𝛽) plaques and activation of the  nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome is linked with the development of Alzheimer’s disease (AD) later in life. AD is a form of progressive disease that impairs memory and other cognitive functions and impacts the lives of tens of millions of people globally. This study aims to confirm the linkage between exposure to DEP and memory impairment through NLRP3 inflammasome activation, utilizing an animal model to investigate a potential increase in AD later in life. We exposed male and female low-density lipoprotein receptor knockout (LDLR KO) mice chronically to inhaled DEP or filtered air as a control for 18 weeks. We then utilized the Object Location Memory (OLM) and Object Recognition Memory (ORM) behavioral tests to investigate the immediate impact of multi-week DEP exposure on short-term memory, another indicator in AD progression. Afterward, we sacrificed the mice and harvested a variety of tissues, including the brain. I conducted Immunohistochemistry (IHC) on cryosections of the exposed and non-exposed brain to assess DEP-induced AD-like brain architectural changes and to quantify the impact of DEP exposure in activating the NLRP3 inflammasome, ultimately leading to neurotoxicity, and to the development and progression of AD. Confirming the association between diesel exhaust and the NLRP3 pathway provides a potential therapeutic target in populations at an elevated risk for AD.

Family medicine requires effective dissemination of its growing research base to inform practice, education, and policy. The new Consensus Reporting Items for Studies in Primary Care (CRISP) guidelines may contribute to success. We will describe the pathways primary care (PC) research follows from presentation to publication and test if encouragement to use the CRISP guidelines is associated with increased acceptance and publication rates. We are conducting a confidential online survey in two phases of everyone who presented original research at the November 2023 meeting of NAPCRG (North American Primary Care Research Group), using the Qualtrics platform. Currently in progress, Phase 1 collects data on presenters, studies, research reports, author teams, submission processes, acceptance rates, and publication outcomes. Bivariate and multivariate analyses will identify factors associated with submission, acceptance, and publication. In Phase 2, a randomized controlled trial (RCT) will assign participants to either an observation-only control group or an intervention group receiving the CRISP guidelines. A follow-up survey at 6-9 months will assess presenters’ experiences with acceptance and publication of their written reports. The ongoing Phase 1 survey of 659 presenters worldwide includes diverse professions, specialties, scientific disciplines, and research roles. The presented studies include a broad range of research methods, study designs, problems, populations, and research questions. We will describe presenter experience with the submission, acceptance, and publication of these studies and examine associations with characteristics of the researchers, studies, and reports. The later Phase 2 RCT and follow-up survey will test for differences between the CRISP guideline group and the observation-only control group in success with acceptance and publication. Study results will describe the current practices and patterns of submitting and publishing reports of PC research to guide the dissemination and implementation of research findings to help improve patient care and population health.

In the US, our primary healthcare is mostly delivered via the fee-for-service model. Interactions between providers and patients under this model are mediated by insurance companies. In order to bypass health insurance companies, some primary care physicians have opened direct primary care clinics which charge a monthly fee for unlimited care. As part of my undergraduate thesis for the anthropology honors program, I investigated two clinics operating under this model in the Pacific Northwest using participant observation and semi-structured interviews with physicians. My aim was to determine how the direct primary care model affects the agency of physicians and influences the therapeutic process via the clinical encounter. I found that physicians in the US face a unique dilemma of role conflict between the competing identities of business owner and doctor. Additionally, I explored how the expectations of patients differ for male and female physicians and how direct primary care can play into this. My findings highlighted the inadequacies of our existing healthcare system in the United States. Further, I concluded that although direct primary care is a solution to this broken system for some patients and some physicians, systemic changes must be made in order to make primary care a more desirable field for physicians and to provide equitable and quality care for all patients.

Consumption of highly reinforcing drugs, such as cocaine, can result in an escalation of drug consumption. Escalation is related to the most severe consequences associated with substance use disorder (SUD), including overdose. Chronic substance use leads to neurobiological changes including the signaling of the stress-related peptide corticotropin-releasing factor (CRF). Previous work has implicated CRF dysregulation in alcohol, psychostimulant, nicotine, and opioid dependence. CRF release in extrahypothalamic regions contributes to anxiety-like symptoms of withdrawal that can motivate individuals to consume drugs. There is limited evidence addressing whether CRF receptor (CRFR) activation alters cocaine consumption in individuals who have escalated their cocaine consumption. Additionally, the majority of the previous work has primarily been conducted in male subjects. The present study examines the underlying neurobiology of escalated cocaine consumption in male and female rats. Wistar rats were trained on long access (6hr) cocaine self-administration paradigm in which a subset demonstrated an escalation in their cocaine consumption. At the end of this paradigm, rats were subject to systemic administration of one of two CRFR1 antagonists, antalarmin (25mg/kg, i.p.) or N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5a]pyrimidin-7-amine (MPZP; 10 and 27.5 mg/kg, s.c.). I hypothesize, following previous work, that antalarmin and MPZP will both significantly reduce escalated cocaine consumption in rats classified as escalators but not non-escalators. These results would indicate that CRFR1 activation mediates escalated cocaine consumption in both male and female rats and may be a valuable target of clinical investigation into the neurobiological underpinnings of this dangerous facet of SUDs.

The Field of Cultural Mediation, along with Linguistic Mediation, has gained popularity in Italy as the country is increasingly a destination for immigration. As EU migration policies have become more selective, solidifying dangerous paths for “irregular migration” such as the Mediterranean and Balkan routes, reception systems become more complicated, borders become more violent, and public opinion polarizes (Lo Bianco, personal communication, 2023). In this context, it is increasingly important to ensure migrants have someone to facilitate communication between them and the various actors they encounter in an increasingly complicated and dispersed reception system built to dispel them. Thus, the Cultural Mediator, often a former migrant themselves, is increasingly employed by public institutions and social cooperatives to facilitate communication, integration, and to inform newcomers of their rights (Cuiban, 2019). There is inherent precariousness in being placed between these two often conflicting sides, requiring a high degree of social, emotional, and institutional expertise in addition to mere linguistic and cultural knowledge. Due to a lack of national regulation and decentralization, Cultural Mediators in Italy face social and emotional difficulties as well a lack of respect, proper regulation, payment, and support in their jobs. In this paper, I investigate the struggles Cultural Mediators in Italy face, which I argue is a product of the broader decentralization of the “Migration Industry”. By conducting surveys and Interviews regarding the Struggles Cultural Mediators in Italy face in comparison to existing primary and secondary resources, I aim to identify these struggles as well as their contexts.

Substance use disorder (SUD) takes a tremendous toll on human life every year, which makes understanding the underlying neural circuitry behind SUD a very high priority. A key neurotransmitter in the discussion surrounding SUD is dopamine, which has been implicated in mediating reward-seeking and motivational behavior. More specifically, these behaviors are believed to be mediated by the dopaminergic projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). Using contemporary technologies like fiber photometry paired with dopamine biosensors, live dopamine dynamics can be viewed in real time and aligned to certain behavior events collected during tasks performed by animals to further understand dopamine dynamics relating to SUD. With this in mind, we injected a cohort of male and female Wistar rats with a viral vector containing the dopamine biosensor dLight, which fluoresces when bound to dopamine, into the NAc and implanted fiber optic cannulas directly above the injection site to monitor the transmission of dopamine in real time during drug consumption. From there, we ran the cohort through a drug self administration cycle consisting of a training period, short access sessions to establish baseline drug consumption (1hr), and finally long access sessions (6hr) which is known to produce escalation of drug consumption, an SUD-like phenotype. Dopamine dynamics were recorded during several time points across this task. We then performed data analysis to assess various relationships between the behavioral and photometry data, along with immunohistochemistry to confirm the injection. Understanding the dopamine dynamics underlying drug consumption and how they change across changing behavior, such as escalation of drug consumption, is essential to building our understanding of SUD, and our current research helps to illuminate the inner workings of that relationship.

When a landslide impacts a river, it may form a dam that blocks the flow of water and builds up a lake. These lakes are prone to sudden outbursts, where they rapidly drain and catastrophically flood downstream areas. Recent UW research has estimated how susceptible rivers in the Oregon Coast Range are to landslide dam formation. However, where these outburst floods would be most dangerous for humans remains unknown. In this project, we ask in which Oregon Coast Range drainage basins are the flood risk and vulnerability the highest. In other words, where would a landslide dam cause the most harm? To answer this, we follow a GIS based methodology for computing flood risk for the Oregon Coast Range. We assess the magnitude of the flood risk in the study area. We define risk as the amount of people (or building footprints) that may be exposed to future flooding hazards. We will also be assessing flood vulnerability, which we calculate using population demographic data. Using these results, we will analyze flood risk and vulnerability in concert with the probability of landslide dam flooding to determine which areas should be highlighted for further detailed study and possible mitigation planning.
 

Inhalation toxicology is a rising field of study as respirable toxicants become increasingly prevalent in our environment. Our research focuses on commonly inhaled toxicants: diesel exhaust (DE) and electronic cigarette aerosols (e-cig). Exposure to traffic-related air pollution and the use of e-cigs has rapidly increased, yet molecular pathways and health effects, and innate factors that impact health outcomes, remain largely unexplored. To assess cardiometabolic and neurodegenerative effects of DE, we exposed male and female mice (low-density lipoprotein receptor knockout, Ldlr KO) to filtered air or freshly generated DE for 18 weeks while fed a high-fat or Chow diet. We then conducted Object-Recognition and Object-Location Memory neurobehavioral tests to assess cognition, specifically hippocampus-independent recognition memory and hippocampus-dependent spatial memory and discrimination, respectively. We sacrificed mice and harvested brain, liver, and lung tissue for histopathological staining and biochemical measurements, including 3-nitrotyrosine, a biomarker of oxidative stress, via Western blot. To assess cardiopulmonary effects of e-cig aerosols, we exposed different mouse strains to acute (5 days) and chronic (3 months) e-cig aerosols with and without nicotine. We then harvested lung tissue and quantified glutathione (reduced and oxidized), an antioxidant and essential nucleophilic scavenger of electrophiles, via high-pressure liquid chromatography; and protein 3-nitrotyrosine. Statistical analyses of all the results obtained were carried out using R. Initial results revealed sex differences in biomarker levels between control and exposed mice. We plan to expand analyses by measuring an additional biomarker of oxidative stress, 8-oxo-dG. Additionally, we will quantify heavy metal accumulation in liver and brain in DE-exposed mice, along with metabolites of carcinogens such as acrolein in e-cig exposed mice. Forthcoming measurements will provide a more comprehensive understanding of biological responses to exposures and elucidate potential health implications. Our research in inhaled toxicants helps reveal critical insights for emerging public health challenges.

Merkel cell carcinoma (MCC) is a rare and aggressive cancer of the skin with a mortality rate of ~30%. In the US, most MCC tumors arise from integration of the Merkel cell polyomavirus (MCPyV) DNA into a host chromosome, leading to expression of viral T-Antigen (T-Ag) oncoproteins that drive tumorigenesis. Though current treatment options have significantly improved MCC prognosis, new therapies are needed to address recurrent/resistant disease. While T-Ag-specific antibodies are usually detected in the blood of patients with virus-driven MCC, the role of these antibodies in tumor immunity remains unclear. Here, we analyzed blood samples from 100 MCC patients prior to definitive treatment, 51 of whom had high titers of antibodies recognizing the T-Ags. These 51 high titer samples were assessed for binding across two domains of the T-Ag. Suprisingly, we found that patients who had high titers of antibodies binding both regions of the T-Ag had worse MCC control than patients whose antibodies predominantly bound one region (median PFS 5.5 vs. 14.2 months, p=0.003). These data suggest that careful mapping of circulating antibody reactivity to different regions of T-Ag can serve as a biomarker to identify high-risk patients for which a more aggressive treatment regimen is needed. Future work is also focused on understanding the immune response resulting in differential response to T-Ag domains.

Merkel cell carcinoma (MCC) is rare and aggressive skin cancer with high risk of metastasis. Developments of PD-1/PD-L1 immunotherapy has significantly improved treatment outcomes of metastatic MCC. Unfortunately, only 50% of patients demonstrate long-term responses. Previous studies by our lab have demonstrated that infiltration of CD8+ T cells in MCC tumors correlates to long-term responses. However, the impact of other innate immune cells and lymphocytes remains unclear. I hypothesize that the spatial interaction of pro-inflammatory cells (primarily T and B cells) associate with better outcomes in the absence of suppressive macrophages that disrupt this immunological crosstalk. To investigate this, I have been using QuPath, a spatial analysis software, to examine the microenvironments of 75 MCC tumors. These tumors have been stained with 18-marker antibody panel to identify subsets of B, T, and innate immune cells. Using QuPath, I have been quantifying different immune cell populations, as well as investigating their spatial relationship to each other. Using this data, I have been working with a PhD student and Dr. Paul Nghiem, to correlate this immunological data to clinical outcomes. Our preliminary data demonstrates that high B-cell infiltration may correlate with better clinical outcomes. While this is promising, I plan to expand my studies, investigating the impact of other innate immune cells on immunotherapy outcomes. I will then work to validate my studies by investigating a different cohort of 35 MCC tumors taken from a recent immunotherapy clinical trial. By investigating the tumor microenvironment, my goal is to help identify which population of cells associate with better responses. This in turn may lead to a diagnostic assay that may help assess cancer aggressiveness, which physicians can use to tailor treatment course. In addition, this information can help guide future drug development, showcasing which cells are the most important to target and/or enhance.

The COVID-19 pandemic has brought to our attention the lack of fast, affordable, and sensitive diagnostic tests available on the market. The majority of commercial diagnostic tools are expensive, despite being quick and sensitive. This conundrum has brought attention to the necessity for developing high-quality tests at an affordable cost, emphasizing the importance of accessible diagnostics that are both rapid and sensitive. The Yager lab has been developing detection tools for infectious diseases, mainly based on isothermal nucleic acid amplification tests, using loop-mediated isothermal amplification (LAMP). The LAMP assay includes a DNA polymerase known as Bst. It was found that assay sensitivity improved when the samples were pretreated with HUDSON, which consists of TCEP (a reducing agent) and EDTA. I am investigating the improvement of Bst DNA polymerase activity with TCEP, using a commercial enzyme kinetics kit (EvaEZ) to quantify the Bst polymerase activity. The EvaEZ assay allows quantitative comparison between conditions by measuring fluorescence intensity indicative of DNA amplification. This was achieved by assessing primer binding, enzymatic extension, and EvaGreen dye intercalation, enabling comparison of the rates of fluorescence generation to evaluate amplification efficiency across positive, negative, and experimental control conditions. This project is still ongoing, and preliminary findings suggest promising results. This study demonstrates the potential for using reducing agents to optimize enzyme efficiency and improve detection sensitivity. This technique can readily improve detection speed and sensitivity both simply and affordably. We are able to be better prepared for the next pandemic.

Alzheimer's disease (AD), the most common form of dementia, is characterized by the improper cleavage of amyloid precursor protein by a complex containing presenilin 1 (PSEN1) or presenilin 2 (PSEN2). Notably, PSEN1 and PSEN2 are strong genetic risk factors for heritable AD. However, 95% of AD cases currently have no known genetic cause. Recent work from the Valdmanis lab found PSEN2 isoform variations at the RNA level in sporadic AD. One such variation was the detection of differential 3'UTR lengths on the PSEN2 transcript. The 3'UTR is an important regulatory region that controls transcript maturation, stability, and abundance and is subject to environmental regulation. The length of this regulatory region is determined by RNA processing machinery during polyadenylation, and differences in this post-transcriptional process lead to differences in the 3'UTR length known as alternative polyadenylation (APA). APA may represent a functional mechanism by which PSEN2 regulation differs in AD. The goal of these studies is to understand the impact of PSEN2 APA on neuronal function. We hypothesize that the length of the 3'UTR on PSEN2 transcript aligns with phenotypic changes associated with AD. To test this hypothesis, we are cloning PSEN2 with short and long 3'UTRs to test the functional differences of PSEN2 APA in vitro. Our goal is to introduce the short and long PSEN2 3'UTR constructs in the cells, specifically, microglia, the brain's immune cells, which are heavily implicated in AD pathology. Then, we will visualize the subcellular location of these transcripts and test for altered amyloid beta processing, which is a pathological hallmark of AD. We anticipate detecting differences in regulation and subcellular localization between the short and long PSEN2 3'UTR transcripts. Elucidating the functional relevance of the short and long 3'UTR of the PSEN2 transcript will further our understanding of APA in AD.

This poster describes a qualitative study highlighting the intersection of ethnic identity and Christian faith in shaping South Asian college students’ perceptions of LGBTQ+ individuals. Current sociopolitical climates toward LGBTQ+ individuals in South Asian countries tend to be hostile, and even South Asian communities within the United States can reflect similar beliefs. Zaidi (2014) found that shame in the South Asian community was in conflict with a desire to express one’s queer identity among South Asian youths (Zaidi, 2014). Moreover, environmental factors such as the religious setting might contribute to varying perspectives regarding LGBTQ+ individuals; in the current study, we highlight faith-based higher education institutions (i.e., Christian university) as an institution that can shape views regarding LBTBQ+ folks and their experiences. We conducted 6 semi-structured interviews with South Asian college students enrolled in a Christian university located in the Pacific Northwest region of the U.S. Our three-member research team transcribed the interviews, coded the transcriptions, and placed the codes in themes according to Braun and Clarke’s (2006) guidelines for Thematic Analysis. The four themes that we identified include support for LGBTQ+ people on campus, Christian messaging around LGBTQ+ identity, South Asian communities, and participant’s own attitudes. These major themes also included subthemes, some of which are campus advocacy and protests influenced participant’s beliefs, feelings of an internal struggle, attitudes of South Asian communities, and individual affirming attitudes. Broadly, we found that the participants viewed their own South Asian communities as generally silent or passive in LGBTQ+ dialogues, and that their Christian campus promoted both helpful and unhelpful conversations about the topic. We will present some implications for practice in higher education around fostering an inclusive space for LGTBQ+ individuals, especially as they pertain to intentional integration of culture-specific (e.g., South Asian) and religious (e.g., Christian) perspectives.