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No full textThe author submitted this entry in the 10-Word Story category (Amateur division) for the 2024 On My Own Time (OMOT) Art Show.A morbid thought from working with a caffeine-addicted pathologist
Factors That Influence Murine Norovirus Stability and Tropism
Get PDFIn this work I investigated factors that influence murine norovirus stability and tropism through two independent projects. Murine norovirus (MNV) is a model system used to study human noroviruses due to its robust replication in cell culture and mouse model. I first investigated the interactions between MNV and bacteria in vitro by determining what bacteria and bacterial components could impact viral thermostability. I found that that specific Gram-positive bacteria and conditioned medium from Gram-positive bacteria could stabilize MNV against heat inactivation. However, I found that Gram-negative bacteria and conditioned medium had no impact on viral stability. These stabilizing effects of bacteria may play a role in viral transmission due to the fact that the virus must remain stable in the environment to transmit to a new host. In my second project I used a forward genetic approach to select for MNV variants with increased host cell range. I found that by serially passaging murine norovirus in human HeLa cells I could select for mutant viruses that increased replication as compared with the parental strain in a non-natural host. The passaged viruses had many mutations spanning the viral genome, however I determined three specific mutations in the NS1/2 protein that allowed for the virus to grow better in human cells. I determined that the adapted viruses have increased replication because they overcame a post-entry replication block in HeLa cells, not because they have increased attachment. This was surprising given that HeLa cells do not have the MNV receptor. These studies show that MNV tropism is not only determined by receptor availability. Overall, these studies illuminate unique aspects of MNV biology that may be applicable to other viruses
A better way to leave: how physicians and universities benefit from a focus on parental leave transitions
Get PDFDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin
If You Build It, They May Not Come
Get PDFIn a desire to create something engaging for National Public Health Week in April, we developed a virtual escape room that would highlight public health information. A narrative was created first (an old hospital library) and which facts about Public Health to include were decided. A variety of free, online resources were utilized to develop puzzles and images that would aid in opening the four locks including a coded quote, a puzzle, a rebus, and a maze. PowerPoint was used to create composite images using free images from Pixaby and Creative Commons Images. Some images were created using other tools including AI. SpringShare LibWizard was the platform chosen to hold the escape room. Through it all, players were encouraged to solve the next puzzle before the hospital was demolished around them. The final version was trialed among library staff to work out errors and inconsistencies. Unfortunately, the escape room was not well received despite extensive marketing to both the School of Public Health and the medical center campus at large. Only 35 people attempted the challenge and fewer than 20 finished it. While there was disappointment that the escape room was not more well received, it was not deemed a failure. While time consuming to create and develop, we could see other applications for this particular tool within the library's learning resources including creating an escape room to provide one mode of library orientation
New treatments for anemia, ischemia, and cancer emerging from studies of von Hippel-Lindau Disease
Get PDFDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin
Optimizing Opioid Prescription for Outpatient Surgery
Get PDFINTRODUCTION: Opioid overprescribing by surgeons has contributed to the current opioid epidemic. This has occurred both from the transition of patients to chronic opioid use after initial use for acute pain only and from diversion of unused opioids from prescriptions intended for acute surgical pain. Factors leading to overprescribing by surgeons include historical misinformation about the addictive nature of opioids, societal and governmental expectations, and lack of standard prescribing guidelines. Multiple academic medical centers have developed opioid stewardship programs to study, optimize, and standardize opioid prescribing after surgery through consensus of all relevant stakeholders without changes to patient satisfaction or pain control.
OBJECTIVE: No similar guidelines existed at the University of Texas Southwestern Medical Center's Clements University Hospital for acute surgical pain prescription oversight. Our project centered around developing an opioid stewardship program at our own institution using existing resources to align opioid prescribing after common day surgery procedures with established guidelines published by other major institutions.
METHODS: We developed a multitiered approach for our opioid stewardship program. This included developing a database, providing educational opportunities to prescribers, and implementing process change in EPIC workflow. Our multidisciplinary team analyzed surgery billing information and EPIC pharmacy data for prescriber type, strength, and average number of pills/dosage of each opioid prescription. Procedures initially targeted included laparoscopic cholecystectomies, laparoscopic appendectomies, inguinal hernia repairs (both open and laparoscopic), and umbilical hernia repairs. To standardize measurements, prescriptions were converted to morphine milligram equivalent (MME), where one opioid tablet= Oxycodone 5mg= MME of 7.5 per tablet. Data was compared to current Outpatient Procedure Guidelines as set forth by the University of Michigan and Johns Hopkins University. A dashboard was created for physicians using collected data to enable review of prescribing habits. Small and large group education sessions on prescribing guidelines were implemented targeting attendings and residents. We identified areas of potential improvement in existing process and changed EPIC order-sets and quantity defaults for prescriptions after routine outpatient procedures.
RESULTS: A prescription database was created and formatted for easy analysis in Tableau. Preliminary analysis suggests residents write more than 80% of prescriptions following routine outpatient surgical procedures. Tylenol #3 and Tramadol are the most commonly prescribed. Large variation exists regarding the type and quantity of the opioid medication prescribed. There appears to be a clear downward trend each year in the average MME prescribed, particularly following initial interventions in the summer of 2018, however no robust statistical analysis has yet been performed. There also appears to be less variation in MME and type of medication prescribed beginning in 2017. Educational opportunities in the form of small group and Grand Rounds were offered to faculty, residents and students. EPIC order-sets were implemented within our system for the prescribing of opioids following outpatient procedures and defaults within EPIC were changed.
CONCLUSIONS: It is possible to set up a multidisciplinary multi-tiered opioid stewardship program using existing resources. Residents are the primary prescribers of opioids at our institution and targeting this group remains a high priority of the authors of this study. Smaller quantities of opioids are being prescribed after targeted surgical procedures over time post-intervention, and it appears that opioid quantities being prescribed are aligning more closely with published guidelines
Novel Functions of the Transcription Factor Aryl Hydrocarbon Receptor (AHR) and Its Tryptophan-Derived Ligands in Cancer Cells
Get PDFThis comprehensive study delves into the metabolic reprogramming of cancer cells, focusing on the proto-oncogene MYC and the aryl hydrocarbon receptor (AHR). The role of MYC in regulating tryptophan (Trp) metabolism was investigated in colon and liver cancer cells using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our findings reveal that MYC enhances the intracellular levels of Trp and its metabolites in the kynurenine pathway, specifically increasing the expression of Trp transporters SLC7A5, SLC1A5, and the enzyme AFMID. Elevated levels of these components were observed in immortalized colon cancer cells lines and patient tissues, with a significant increase in kynurenine. Blocking enzymes in this pathway led to the preferential death of cancer cells, suggesting a potential therapeutic strategy. Furthermore, our research highlights the role of AHR in cellular detoxification and proliferation, particularly in MYC-overexpressing cells. We found that AHR knockdown reduced the expression of genes crucial for metabolic pathways necessary for cell proliferation, such as LDHA, DHODH, and UMPS. Additionally, we identified SCIN, an actin-severing protein, as a key target of AHR in colon cancer cells, necessary for cell proliferation and activation of the WNT pathway through β-catenin. In liver cancer, we discovered that MYC-driven tumors have a critical dependence on Trp, with a diminished utilization of the Trp via the Kyn pathway. Depriving these tumors of Trp inhibits their growth, while supplementation with the Trp metabolite I3P restores growth, presenting a novel therapeutic target. Overall, our findings underscore the importance of MYC and AHR in regulating amino acid metabolism in cancer and open new avenues for targeted cancer therapies
Training Regime
Get PDFThe author submitted this entry in the Open Verse Poetry category (Professional division) for the 2024 On My Own Time (OMOT) Art Show.I wrote this poem after Sage Kotsenburg, first Olympic gold medalist in Snowboard Slopestyle, won a contest called Natural Selection. It was his return to competition after walking away shortly after his Olympic victory due to the pressure. He was a new man, and I've noticed other Olympic snowboarders experiencing a similar struggle with what's supposed to be your greatest achievement and a sense of dissatisfaction. I wanted to explore those emotions in my poem
Intestinal Epithelial Cell Intrinsic IL-1R Signaling in Host Defense and Inflammation
No full textPages viii-xix are misnumbered as pages vi-xvii.Intestinal epithelial cells (IECs) constitute a critical first line of defense against microbes by providing a physical barrier and producing antimicrobial peptides (AMPs) and cytokines. While IECs are known to respond to various microbial signals, the precise upstream cues regulating diverse IEC responses are not clear. Here we discover a dual role for IEC intrinsic interleukin-1 receptor (IL-1R) signaling in regulating both intestinal homeostasis and inflammation. Specifically, absence of IL-1R in epithelial cells abrogates a homeostatic antimicrobial program including production of AMPs. Mice deficient for IEC intrinsic IL-1R are unable to clear Citrobacter rodentium and have impaired AMP gene expression during infection. Mechanistically, IL-1R signaling enhances IL-22R induced STAT3 phosphorylation in IECs leading to elevated production of AMPs. A similar synergy between IL-1β and IL-22 was found in human IECs. We find that IL-1R signaling on IECs directly induces expression of chemokines as well as genes involved in the production of reactive oxygen species in IECs. Absence of IL-1R in IECs protected mice from chemically induced colitis, suggesting that IEC intrinsic IL-1R signaling contributes to worsened inflammation and pathology during acute inflammation. Our findings establish a protective role for IEC intrinsic IL-1R signaling in combating infections, and a detrimental role of IEC intrinsic IL-1R signaling during colitis induced by epithelial damage
Clinical Features and Outcomes of Black Patients with Melanoma: A Case Series Between 2006-2022
No full textThe 62nd Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 30, 2024, 3-6 p.m., D1.700 Lecture Hall)BACKGROUND: The incidence of melanoma in Black patients is rare, therefore most studies describing outcomes have been performed using population databases with limited patient-level information.
OBJECTIVE: To describe specific anatomic sites, clinical features, histologic subtypes, risk factors, and outcomes of Black patients with melanoma.
METHODS: Case series of Black patients with melanoma identified between January 2006 and October 2022 at University of Texas Southwestern Medical Center and Parkland Health in Dallas, TX. Participants included self-identified Black patients with a histopathologic diagnosis of melanoma. Data collection included demographics, clinical characteristics, personal and family medical history, immunosuppression history, comorbidities, histopathology reports, imaging reports, melanoma treatments and responses, time to progression, metastatic sites, and survival. Kaplan-Meier analysis captured melanoma-related survival by primary site.
RESULTS: Of the 48 patients identified, the median age at diagnosis of melanoma was 61.5 (range: 23-86) with the majority being female (30/48). Seventy-five percent (30/40) of primary cutaneous melanomas were located on acral skin despite only one-third (10/30) being histologically classified as acral lentiginous melanomas. Compared to those with acral disease, patients with non-acral cutaneous melanomas were more likely to be immunocompromised (40% vs. 7%) or have a personal history of cancer (60% vs. 17%) with all (3/3) superficial spreading melanoma patients having a history of both. No patients had more than 1 confirmed primary melanoma. In total, 13 (27%) Black patients with melanoma developed stage IV disease, of which 12 ultimately died due to disease progression. Those diagnosed with advanced acral melanoma, mucosal/ocular melanoma, or unknown primary had the poorest melanoma outcomes. No patients with non- acral cutaneous melanomas developed distant metastases or died of their disease.
CONCLUSION: Most cutaneous melanomas in Black patients occur on acral sites. Non-acral cutaneous melanomas had limited contribution to melanoma mortality in Black patients and were diagnosed primarily in immunocompromised patients or those with a history of other cancers. Improving melanoma mortality in Black patients will require focused therapeutic and early detection strategies for acral, mucosal/ocular, and melanoma of unknown primary.Southwestern Medical Foundatio