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Improving Intra-Operative Parathyroid Hormone Result Times at the University Hospitals
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.Intra-operative parathyroid hormone (ioPTH) levels are the current gold standard for assessing completeness of resection in parathyroidectomy surgery. Due to the time-sensitive nature of these results, delays in processing ioPTH samples lead to non-value-added time (NVAT) in the operating room, which generates unnecessary financial burdens and potential safety hazards for both patients and the hospital system.
Baseline analysis of data from 191 parathyroidectomy cases performed by the UT Southwestern Endocrine Surgery Group at Clements University Hospital (CUH) and the Outpatient Surgery Center (OSC) between September 2020 and April 2021 identified a statistically significant delay in the sample-to-lab interval time in cases at the OSC (mean of 27 minutes) compared to cases at CUH (mean of 8 minutes). The need for a lab courier at the OSC is likely a major contributor to this NVAT, as the OSC does not have an in-house lab. Though altering the lab infrastructure to make in-house ioPTH processing at the OSC would be the most effective way to equalize the delay, it was also infeasible within the time constraints of this project given the depth of high-level decision-making this would necessitate.
I chose to focus instead on optimizing parathyroidectomy case preparation. I worked with CUH OR nursing clinical leads to modify the Epic template text of surgeon preference cards, which OR nursing staff use to prepare for cases. Analysis of pre- and post-change data from 43 parathyroidectomy cases performed in February and March of 2022 at CUH revealed post-change special cause variation in both the sample-to-lab and lab-to-result interval times. Moving forward, many other interventions are available to continue to improve team communication and knowledge sharing and protocolize contingency plans; further work also remains to be done to address logistical constraints at the OSC on an institutional level
Incorporating Real-Time Audiovisual and Haptic Feedback in a Novel Thoracostomy Tube Training Model
Get PDFThe 62nd Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 30, 2024, 3-6 p.m., D1.700 Lecture Hall)INTRODUCTION: Simulation-based training can enhance clinical performance, but chest tube insertion is challenging to simulate due to the precision needed for controlled pleural entry. This study evaluates the efficacy of a novel training model with real-time pressure monitoring and audiovisual feedback for force and time to pleural entry in a model.
METHODS: The model consisted of a Kelly clamp with force sensors installed at the index finger (sensor 1) and both finger loops (sensors 2 and 3) and a manikin with a replaceable chest wall pad. Data obtained from experts indicated standard force value for pleural entry (Newtons, "N") and acceptable time to completion (3000-5000 milliseconds, "ms"). Thirteen participants ranging from PGY-1 to PGY-6 were introduced to the procedure and model. Force and time were measured from dermal entry to pleural space puncture. A significant drop in pressure suggested puncturing through the chest wall.
RESULTS: Force was measured in the linear, plateau, and drop phases of the procedure. Linear phase (~3,000ms) was from start to point of maximum force (5 Newtons within 150ms indicating procedure completion (pleural entry). All participants successfully completed the task. Pleural entry force ranged from 17N to 30N, and time to pleural entry ranged from 7,500-15,000ms. Of note, left-handed participants relied more on sensors 1 and 3 while right-handed participants relied more on sensors 1 and 2. Thus, only force measurements from sensor 1 were utilized to standardize our assessment.
CONCLUSIONS: This novel chest tube trainer with continuous force monitoring can be applied to training for a variety of scenarios, including vascular access, trocar placement and other common procedures. Next steps involve evaluating its impact on trainee accuracy and efficiency.Southwestern Medical Foundatio
Myogenic Effectors and Disease
No full textSkeletal muscle is essential for life. Inside muscle fibers, filaments of actin and myosin slide on each other to generate the mechanical forces that drive muscle contraction, movement, and breathing. Mutations in muscle-related genes can cause severe diseases in humans. Here we characterize the role of three understudied muscle-specific genes and their potential contribution to human disease. We show that constitutive and juvenile loss of the nuclear envelope protein Net39 in mice recapitulates different manifestations of Emery-Dreifuss muscular dystrophy. Deletion of Net39 caused disruption of nuclear envelope integrity and associated genomic, transcriptional, and metabolic changes that compromised muscle function. Mechanistically, Net39 regulates nuclear organization by associating with LEM proteins, and gene expression by controlling the transcription factor Mef2c. In contrast, global deletion of the Kelch protein Klhl41 in mice causes severe nemaline myopathy, including neonatal lethality and aggregation of contractile proteins in muscle, particularly Nebulin. Molecularly, Klhl41 acts as a chaperone for Nebulin, and N-terminal poly-ubiquitination of Klhl41 acts as a signal to regulate its activity. Finally, we identify a novel pathogenic mutation in the cell fusogen Myomixer. We show that patients with Carey-Fineman-Ziter syndrome lose a region of Myomixer required to destabilize opposing cell membranes during myoblast fusion. Overall, our findings here highlight the contribution of understudied genes to muscle biology and the molecular etiology of muscle disorders
Proteasome-Mediated Degradation of PNPLA3
No full textPages 33-49 are misnumbered as pages 34-50, pages 50-75 are misnumbered as pages 52-77, and pages 76-133 are misnumbered as pages 75-132.A missense mutation in PNPLA3 (148M) is the strongest genetic risk factor for fatty liver disease (FLD). PNPLA3 (148M) evades ubiquitylation and proteasomal degradation, and accumulates on hepatic lipid droplets (LDs). E3 Ubiquitin Ligases provides specificity to ubiquitin-mediated proteasomal degradation of proteins in cells. The goal of this project was to identify the E3 Ubiquitin Ligase(s) involved in PNPLA3 degradation. Identification of this ligase will provide a molecular handle on PNPLA3 degradation, and enable us to determine how PNPLA3 (148M) evades degradation by the ubiquitin-proteasome system. We used an RNAi screen in cultured human hepatoma cells and identified Bifunctional Apoptosis Regulator (BFAR) as a candidate E3 Ubiquitin Ligase in the proteasomal degradation of PNPLA3. Further validation of BFAR in liver-derived and non-liver derived cultured cells confirmed its role in promoting the degradation of PNPLA3. We further show that PNPLA3 undergoes polyubiquitination in the presence of BFAR in-vitro and also in cultured cells, establishing it as a direct substrate for BFAR. However, experiments showing PNPLA3 accumulation in BFAR-deficient cells treated with a proteasomal inhibitor also raises the possibility that more than one E3 Ubiquitin Ligase contributes to the degradation of PNPLA3. PNPLA3 (148M) also undergoes proteasomal degradation in the presence of BFAR, which is also consistent with multiple E3 Ubiquitin ligase(s). PNPLA3 is a lipid droplet resident protein, while BFAR localizes in the endoplasmic reticulum (ER). We show that PNPLA3 ubiquitylation is uncoupled from its subcellular localization in LDs. Finally, we observe a modest accumulation of PNPLA3 in hepatic LDs in mice with hepatic depletion of BFAR, which can be due to insufficient reduction in hepatic BFAR proteins or amino acid sequence variation between the species. Future studies with genetically modified murine models will be critical in providing a better mechanistic understanding
The Role of TNRC6 in RNA Interference
Get PDFSmall RNAs can influence translation, splicing, transcriptional activation, and transcriptional repression, through the RNA interference (RNAi) pathway. TNRC6, also known as GW182, and Argonaute (AGO) are the core proteins of RNAi. TNRC6 is a scaffolding protein that associates with AGO and bridges its interactions with other proteins to control gene expression in many different processes. There are three paralogs in mammalian cells, TNRC6A, TNRC6B, and TNRC6C. These paralogs share approximately 40% amino acid sequence identity. Whether the paralogs have unique or redundant functions is unclear.
Much is known about the mechanisms of cytoplasmic RNAi but the world of nuclear RNAi remains murky. We understand that RNAi factors are present and active in the nucleus, but endogenous nuclear RNAi functions are unknown.
I have used a suite of gene knockout cell lines for the TNRC6 paralogs to learn more about TNRC6 paralogs and their roles in RNAi. I examined if TNRC6 paralogs were required in several functions of small duplex RNA-mediated control of gene expression, including translational silencing by miRNAs, translational silencing by siRNAs, and transcriptional activation. On a global scale, I used high-throughput RNA sequencing, mass spectrometry, and enhanced crosslinking immunoprecipitation (eCLIP) to gather definitive answers about the TNRC6 paralogs, their roles in the cell, and their relation to AGO knockout cell lines.
I found that that despite less than 40% sequence identity, the TNRC6 paralogs are functionally redundant and can replace one another for core RNAi functions. Each subsequent TNRC6 paralog knockout caused more gene changes and few genes overlapped between the single TNRC6 paralog knockouts. Changes in levels of gene expression in TNRC6 knockout cell lines are well-correlated with those observed in AGO knockout cell lines, emphasizing the important regulatory function of the partnership between AGO and TNRC6 in endogenous RNAi. Further, I found TNRC6 plays a role in splicing changes initiated by small RNA binding to intronic regions.
Taken together these data further define the roles of the TNRC6 paralogs as part of the RNA interference machinery. TNRC6 is a close protein partner of AGO and serves as a cooperativity coordinator for RNAi
Leadership Styles: Enhancing Motivation and Building Team Collaboration and Engagement
Get PDFLeadership styles vary widely, but three particular approaches stand out in the context of libraries. This lightning talk will explore these three distinct leadership styles and their impact on enhancing workplace motivation. Additionally, I will address strategies for fostering team collaboration and engagement, and how these skills can significantly improve morale in the workplace
Improving Health Disparities to Underserved Populations in Texas Through Teaching Diversity Awareness and Consumer Health Resources to Nursing Students
Get PDFOBJECTIVE: The University partnered with two local community shelters and two organizations in the Texas Rio Grande Valley (RGV) to deliver consumer health resources to individuals. To reduce health disparities/promote healthy behavior, students were taught how to use and promote MedlinePlus and DailyMed while delivering care to individuals in underserved areas of Texas. GOALS: Create awareness of consumer health information by reaching minority individuals. Endorse NLM as a reliable source of health information. Train students to engage in activities that increase representation of NLM teaching and outreach. METHODS: Students were trained to use MedlinePlus and DailyMed databases and then provide resource training to community members in shelters locally and during the University's mission trip to RGV. The number of participating community members and students were kept. CONCLUSION: Funding was provided by the NNLM, Region 3, Health Information Outreach Award. Utilizing Qualtrics surveys, program effectiveness was evaluated on content delivered to students and community members in the local and RGV area. The educational outreach positively impacts Black, African American, and Hispanic individuals served in the local community and in RGV. Outcomes measure the user's trustworthiness and usefulness of the databases following the demonstrations. 281 students and 188 individuals received information about the databases including additional health information
I Need It Now!
Get PDFI need it now! Sound familiar? As the Library has transitioned from a print to digital environment, we've also been told, "the fewer clicks, the better!" From print handouts to a one-stop Library website with online chat, portals/guides dedicated to discipline-specific resources/subject resources/databases, education calendar, electronic Library newsletter and social media to point and click with QR codes! Join our lightening talk as we share how access, use of the Library and its resources and staffing evolved pre-, during and post-COVID-19
The Power of Your Vote: The Impact of Your State Legislation on Library Operations
Get PDFLibraries nationwide are encountering various challenges amidst ongoing confusion and disruption caused by changes in state legislation and administrative codes. This roundtable will bring together librarians from different states to share insights on the proposed laws from their legislative sessions, including which ones passed or failed, their impact on the rights of library users and staff, and strategies for addressing these issues
From DEI to JEDI: The DEI Committees of MLA's Chapters
Get PDFBACKGROUND: The concept of organizations widely giving attention to their diversity, equity, and inclusion (DEI) efforts began several years ago. The Medical Librarian Association (MLA) launched its DEI Task Force in 2017 and in 2020 that task force became a full MLA committee. MLA Chapters have also begun establishing their own formal DEI efforts. There are currently eight MLA chapters that have DEI committees or task forces. This poster illustrates the history of their formation and current status. DESCRIPTION: MLA's South Central Chapter (SCC) decided to establish a DEI task force in 2022. The charge was to investigate whether a standing committee on diversity, equity, and inclusion issues should be formed and make recommendations to the Executive Board. One of the first tasks was to determine how the other MLA chapters decided to create their committees to gauge if SCC could learn from their efforts. The task force also developed and disseminated a membership survey about interest in chapter DEI activities and explored different definitions for DEI concepts. The results of the SCC DEI task force work led to them recommending that the SCC establish a new committee devoted to DEI. CONCLUSION: MLA chapters have followed MLA's lead in committing to DEI efforts, which includes establishing chapter DEI committees and task forces. The SCC chapter is one of the most recent ones to establish its JEDI (Justice, Equity, Diversity, and Inclusion) committee