The National Associations of the Deaf astimates there are 308,648 deaf and hard of hearing D/HH students in the US, 79.2% of D/HH students attend mainstream school. D/HH students tend to stuggle academically and socially in high school which leads to low self-esteem. This project uses a Critical Youth Participatory Action Research (YPAR) ethic, framework, and methodology to put power of research and advocary into the hands of the D/HH youth at a PNW high school. YPAR is an epistemological framework in response to the historical dehumanization of marginalized communities. It democratizes ad decoonizes research by privileging the knowledge production of vulnerable communities and foregrounding justive and change. In practice, YPAR develops research skills of typically non-academic co-researchers who drive the research question, design, and analysis. The aim of this project is to guid the students and build their skills to name the challenges they face as minoritized D/HH students, to collect and analyze relevant data, and to use the data to drive policy. the signifiicance of this project is the methodology thatdemands youth voices to be centered in policy making and cultural change. The expected results are findings that speak to the challenges of D/HH students at a PNW high school. The hope is for the D/HH students to present their finingds to policy and decision makers. There is limited research on D/HH students using YPAR methodology and this research will add the perspectives of D/HH students of the discourse.

Cannabis is the most commonly used drug of abuse used by approximately 2.5% of the world's population. Tetrahydrocannabinol (THC) is the major psychoactive component of cannabis. Cannabidiol (CBD) on the other hand is a pharmacologically active component of cannabis that is not psychoactive. THC is metabolized via cytochrome P450 enzyme-mediated oxidation to 11-hydroxy-THC (11-OH-THC) and subsequently to 11-carboxy-THC (11-COOH-THC). 11-COOH-THC then undergoes glucuronidation to form an acyl glucuronide (AG), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol glucuronide (11-COOH-THC-Glucuronide). CBD is also metabolized via an analogous pathway to THC, where CBD is oxidized to 7-hydroxy cannabidiol (7-OH-CBD) and then subsequently to 7-COOH-CBD and ultimately glucuronidated to form the AG 7-COOH-CBD-Glucuronide. The THC and CBD AGs are important because they circulate at high concentrations in biological samples. Thus, identifying the enzymes responsible for the formation of cannabinoid AGs is important for understanding inter-individual variability and disease effects of cannabinoid exposures and pharmacological effects. Glucuronidation is governed by UDP-glucuronosyltransferases (UGTs). The goal of this study is to identify and characterize the UGTs that form THC and CBD AGs, to define in what organs these glucuronides are formed, and to determine whether disease states may alter 11-COOH-THC and 7-COOH-CBD glucuronidation. To accomplish this I incubated human liver microsomes (HLMs) and recombinant UGTs with 11-COOH-THC (5 µM) or 7-COOH-CBD (5 µM). The incubations were done at pH 7.4, 37℃ for 5 (THC-COOH) or 45 (7-COOH-CBD) minutes. Formation of the THC and CBD AGs was detected in HLMs and with UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT2B7. UGT2B4 and UGT2B17 were specific to THC AG formation and UGT1A10 was specific to CBD AG formation. Kinetic assessments such as intrinsic clearance measurements and inhibition assays will further the understanding of the importance of the specific UGT isoforms responsible for cannabinoid acyl glucuronide formation in vivo.

Cellular retinoic acid binding proteins (CRABP) are soluble proteins that play an important role in binding to retinoids, primarily all-trans-retinoic acid (atRA). RA isomers and their metabolites play a vital role in embryonic development and the central nervous system. CRABP binding regulates retinoid signaling. Retinoid binding affinity to CRABP is described by the equilibrium dissociation constant K_d. CRABP1 interacts with atRA metabolizing enzymes, where relative concentrations of atRA and CRABP1 determine the rate of atRA metabolism. Therefore, measurements of the accurate K_d for endogenous retinoids to CRABP1 are an important aspect of understanding retinoid signaling during development. My goal was to determine the binding affinities of various endogenous retinoids to CRABP1, using a modern fluorescence spectrometric assay and lower CRABP1 concentrations compared to historical methods. The Norris equation was fit to the data to determine the K_d from the decrease of peak tryptophan fluorescence as retinoid bound to CRABP1. The calculated K_d was <1 nM for atRA, 3-10 nM for 4-oxo-atRA, 50-100 nM for 9-cis RA, and near 1 uM for 4-oxo-13-cis and 13-cis RA. When the K_d is much lower than CRABP1 concentration, binding of the retinoid to CRABP1 results in depletion of the retinoid in solution and hence an overestimation of the K_d value. As this work uses lower CRABP1 concentrations than previous studies, the predicted K_d estimates for retinoids that tightly bind to CRABP1 would be lower and more accurate. This is supported by the data. While the K_d of atRA is similar to its endogenous concentration in human plasma, the K_d of the other retinoids tested are much higher than their concentrations, suggesting that small fractions of these retinoids are bound to CRABP1 in vivo. Knowing these K_d values may give insight into how altered CRABP1 concentrations impact development through their modulation of RA concentration.

Adipose tissue, also known as body fat, is vital in storing energy. It is composed of adipocytes and present in different depots. In this study we focused on omental (OM) adipose tissue, which is found between organs near the stomach, and subcutaneous (SC) adipose tissue, which is found under the skin. Functional differences have been observed among adipose depots. SC adipose tissue is responsible for insulation while OM adipose tissue has endocrine functions. OM adipocytes have been observed to be smaller and more variable in size compared to SC adipocytes in individuals with obesity. I hypothesized that the size of both OM and SC adipocytes is associated with increasing BMI. I tested this hypothesis using SC and OM adipose tissue biopsies collected during elective surgeries from metabolically healthy participants (20 females, 11 males) with a range of ages (25-65 years) and BMIs (21-56). Afterwards, the tissues were fixed and stained with H&E. I drew 2-5 squares per slide and counted the number of adipocytes within each square. The size difference between OM and SC adipocytes was tested using a Wilcoxon signed-rank test and a significant difference (p=0.004) was observed. A correlation between BMI and the size of OM (p = 0.008) or SC (p = 0.009) adipocytes was detected with weighted linear regressions. Sex was not observed to be a significant covariate. These findings expand on prior data by including lean individuals, and patients with obesity who are otherwise metabolically healthy. The results show there is a clear difference in the size of adipocytes. The adipocyte size in both depots correlated with BMI. This data shows that progressive obesity and adipose tissue enlargement is due to the enlargement of the adipocytes rather than an increase in the number of adipocytes in both OM and SC depots.