Texas Digital Library
UT Southwestern Medical Center Institutional Repository (University of Texas)Not a member yet
10274 research outputs found
Sort by
It's a C Thing
Get PDFThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show
Identification of Scavenger Receptor B1 as the Airway Microfold Receptor for Mycobacterium tuberculosis
Get PDFMycobacterium tuberculosis (Mtb) can enter the body through multiple routes, including via specialized transcytotic cells called microfold cells (M cell). However, the mechanistic basis for M cell entry remains undefined. Here, I show that M cell transcytosis depdends on the Mtb Type VII secretion machine and its major virulence factor EsxA. I identify scavenger receptor B1 (SR-B1) as an EsxA receptor on airway M cells. SR-B1 is required for Mtb binding to and translocation across M cells in mouse and human tissue. Together, my data demonstrate a previously undescribed role for Mtb EsxA in mucosal invasion and identify SR-B1 as the airway M cell receptor for Mtb
Grief
Get PDFThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.I wrote this on the one-year anniversary of my father's angel wings. My father liked to write poetry and I told myself I would continue to write in his honor. As I reflected on his life and processed all of my emotions on his anniversary, this poem came to my heart and mind. Many of my friends and family and the world is still grieving from so many changes and losses. It takes time to heal. It isn't an easy journey. Writing is therapeutic for me so I hope this can help heal others who also experience grief and that difficult journey. However, I hope as in the poem we all find peace with this journey and this unavoidable part of life. I want to leave with the reader that there is still hope and the feeling of hope
Weightbearing and Activity Restriction Treatments and Quality of Life in Patients with Perthes Disease
No full textBACKGROUND: Weightbearing and activity restrictions are commonly prescribed during the active stages of Perthes disease. These restrictions, ranging from cast or brace treatment with nonweightbearing to full weightbearing with activity restrictions, may have a substantial influence on the physical, mental, and social health of a child. However, their impact on the patient's quality of life is not well-described.
OBJECTIVES: After controlling for confounding variables, are restrictions on weightbearing and activity associated with physical health measures (as expressed by the Patient-Reported Outcome Measurement Information System [PROMIS] mobility, PROMIS pain interference, and PROMIS fatigue), mental health measures (PROMIS depressive symptoms and PROMIS anxiety), and social health measures (PROMIS peer relationships)?
METHODS: Between 2013 and 2020, 211 patients with Perthes disease at a single institution were assigned six PROMIS measures to assess physical, mental, and social health. Patients who met the following eligibility criteria were analyzed: age 8 to 14 years old, completion of six PROMIS measures, English-speaking, and active stage of Perthes disease (Waldenstrom Stage I, II, or III). Weightbearing and activity restrictions were clinically recommended to patients in the initial through early reossification stages of Perthes disease when patients had increasing pain, loss of hip motion, loss of hip containment, progression of femoral head deformity, increased hip synovitis, and femoral head involvement on magnetic resonance imaging (MRI), or as a postoperative regimen. Patients were categorized into four intervention groups based on weightbearing and activity regimen. We excluded 111 patients who did not meet the inclusion criteria. The following six pediatric self-report PROMIS measures were assessed: mobility, pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Analysis of variance (ANOVA) was used to compare differences between the mean PROMIS T-scores of these weightbearing/activity regimens. Results were assessed with a significance of p < 0.05 and adjusted for Waldenstrom stage, gender, age of diagnosis, and history of major surgery using multivariate regression analysis.
RESULTS: After controlling for confounding variables, the mild- (β regression coefficient -15 [95% CI -19 to -10]; p < 0.001), moderate- (β -19 [95% CI -24 to -14]; p < 0.001), and severe- (β -25 [95% CI -30 to -19]; p < 0.001) restriction groups were associated with worse mobility T-scores compared with the no-restriction group, but no association was detected for the pain interference or fatigue measures. Weightbearing and activity restrictions were not associated with mental health measures (depressive symptoms and anxiety). Weightbearing and activity restrictions were not associated with social health measures (peer relationships). Earlier Waldenstrom stage was associated with worse pain interference (β 10 [95% CI 2 to 17]; p = 0.01) and peer relationships scores (β -8 [95% CI -15 to -1]; p = 0.03); female gender was linked with worse depressive symptoms (β 7 [95% CI 2 to 12]; p = 0.005) and peer relationships scores (β -6 [95% CI -12 to 0]; p = 0.04); and earlier age at diagnosis was associated with worse peer relationships scores (β 1 [95% CI 0 to 2]; p = 0.03). History of major surgery had no connection to any of the six PROMIS measures.
CONCLUSION: We found that weightbearing and activity restriction treatments are associated with poorer patient-reported mobility in the active stages of Perthes disease after controlling for confounding variables, but not pain interference, fatigue, depressive symptoms, anxiety, or peer relationships. Understanding how these treatments are associated with Perthes disease patients' quality of life can aid in decision-making for providers, help set expectations for patients and their parents, and provide opportunities for better education and preparation. Because of the chronic nature of Perthes disease, future studies may focus on longitudinal trends in patient-reported outcomes to better understand the overall impact of this disease and its treatment
The Smile
Get PDFThe author submitted this entry in the Fictional Short Story category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.The story, taking inspiration from a local folktale, was created as an exercise in developing a setting and tone for a larger work intended as a period piece horror novel
Why I Will Be Replaced by A.I.
Get PDFThe author submitted this entry in the Open Verse Poetry category (Professional division) for the 2023 On My Own Time (OMOT) Art Show.Like many creatives, I'm concerned about being replaced by artificial intelligence and not a fan of how programs are being trained. At the same time, as a person who occasionally doesn't feel at home in their body, I think it'd be great to just upload my brain into cyberspace and be a sort of A.I. program (although I guess I technically wouldn't be artificial)
Improving Cone-Beam Computed Tomography Based Adaptive Radiation Therapy with Deep Learning
Get PDFDuring radiation therapy, patient anatomical changes may compromise treatment quality if the treatment plan, prepared prior to therapy, remains unchanged throughout the course. Adaptive radiation therapy (ART) has been developed to address this issue by adapting the treatment plan based on up-to-date patient anatomy. The widespread availability of cone-beam computed tomography (CBCT) and its capability for the 3D imaging of patient anatomy has made CBCT-based ART an emerging and increasingly popular technology in the field of radiation oncology. However, numerous challenges persist in the current workflow. One challenge involves generating synthetic CT (sCT) images that retain CBCT anatomy while maintaining CT image quality. Clinically used sCT is typically obtained through deformable image registration (DIR) between pre-planning CT (pCT) and CBCT; however, this method often inadequately preserves CBCT anatomy due to DIR errors. Another challenge stems from the truncation issue in CBCT images, resulting from size limitations of imaging panels, which consequently leads to inaccuracies in CBCT-based dose calculations. Additionally, auto-segmentation of CBCT is impeded by low image quality and a lack of training labels. Although addressing this issue is difficult, enhancing auto-segmentation is essential, as manual segmentation is highly time-consuming. This dissertation aims to improve CBCT-based ART by leveraging deep learning (DL) technologies. First, an unsupervised DL model is proposed to directly convert CBCT images into sCT images with reduced artifacts and more accurate Hounsfield Unit values, as found in CT scans. Second, the model's generalizability is investigated and discussed, along with potential solutions to address the generalizability problem. Third, two DL models are designed to extract and combine information from pCT and CBCT, in order to inpaint axial and longitudinal truncations in CBCT images. Through these three studies, the predicted truncation-free sCT images hold the potential to enhance ART workflows, enabling more accurate dose calculations compared to DIR-generated sCT. The dissertation then shifts its focus to CBCT auto-segmentation. Initially, an unsupervised DL-based DIR model is proposed to predict the deformation vector field between pCT and CBCT, enabling pCT structure propagation as the segmentation on CBCT. To further improve segmentation accuracy, a DL-based direct segmentation model assisted by DIR is proposed, which outperforms state-of-the-art DIR-based segmentation results. The contributions of this thesis are expected to enhance the accuracy and efficiency of sCT generation and CBCT auto-segmentation in the CBCT-based ART workflow
Non-Invasive Eradication of Biofilm on Metal Implants Using Alternating Magnetic Fields (AMF) and Antibiotics
Get PDFHundreds of thousands of human implant procedures require surgical revision each year due to infection. Infections are difficult to treat with conventional antibiotics due to the formation of biofilm on the implant surface. Our group is developing a non-invasive method to eliminate biofilm on metal implants using alternating magnetic fields (AMF), utilizing the physical principle of electromagnetic induction. The aims of this dissertation are to establish exposure parameters for biofilm elimination in the presence and absence of antibiotics, the development of treatment strategies, and investigation the mechanism of AMF towards biofilm. First, the elimination of biofilm on metal implant using intermittent alternating magnetic field (iAMF) and antibiotics was studied, showing iAMF and antibiotics are synergistic in their biofilm reducing capability. For Pseudomonas aeruginosa biofilm, bacterial burden was reduced > 3 log with iAMF and ciprofloxacin after 24 h compared with either treatment alone. This additional treatment effect was also found on Staphylococcus aureus. iAMF and antibiotic efficacy was seen across various iAMF settings, including different iAMF target temperatures, dose durations, and dosing intervals. Initial mechanistic studies revealed membrane disruption as one factor important for AMF enhanced antibacterial activity in the biofilm. Then, the impact factors generated by AMF, heat and electric current, to metal implants were studied separately. A mathematic model was built to describe the response of biofilm to heat based on Arrhenius equation in order to study the responses of various strains to heat. Also, the synergistic effect of heat and antibiotics was observed towards biofilm elimination at various treatment temperatures. Finally, the effect of alternating electric current was studied using a burst AMF (bAMF) strategy, in which negligible heating was produced. For Pseudomonas aeruginosa biofilm, bAMF was able to eliminate biofilm in combination with antibiotics for surface current densities ranging from 99 to 297 A/cm2. This effect was also observed with bAMF and linezolid or rifampin in Staphylococcus aureus but with higher surface current densities required to achieve the same level of biofilm reduction. The results of this study support the use of AMF to reduce biofilm on infected metal implants. The effect can be achieved through both thermal and electrical pathways, or a combination of both. When combined with antibiotics, the effect is amplified and can regularly achieve biofilm eradication. In the future, the results of this thesis can be used to define operating parameters for the non-invasive treatment of infected metal implants
Updates in diabetes technology
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
Developing Humanized PNPLA3 Mice
Get PDFThis poster was presented at the 2023 AMGEN & SURF Scholar Annual Research Symposium as part of the 10-week Summer Undergraduate Research Fellowship Program at UT Southwestern in Dallas, Texas. The research was conducted with the Hobbs-Cohen Lab in the Department of Molecular Genetics.Fatty liver disease (FLD) is the leading cause of liver disease in the world. The disorder begins with an accumulation of triglycerides (TG) in cytoplasmic lipid droplets (LDs). The strongest genetic risk factor for FLD is a missense variant (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3). PNPLA3 is an insulin-regulated gene that is expressed at high levels in liver and adipose tissues. In fasted mice, levels of PNPLA3 mRNA are low and increase after feeding. It has been previously shown that PNPLA3 is a direct target gene of sterol regulatory element (SRE) binding protein 1c (SREBP-1c), and the binding site of the transcription factor was mapped to intron 1. The I148M substitution is located in a region that is well-conserved between mice and humans, so knock-in mice with this variant also develop FLD. Another variant (S453I) in PNPLA3 is associated with reduced hepatic TG levels in humans, but this variant resides in a non-conserved region of the protein. To determine how the S453I variant reduces hepatic TG levels, CRISPR-Cas9 was used to generate mice expressing human PNPLA3. Genotyping indicated that the insertion was successful, and human PNPLA3 protein expression was verified by immunoblotting analysis. Comparing relative mRNA expression levels in fasted versus refed mice demonstrated that human PNPLA3 retained its responsivity to insulin. Future studies can now be conducted using humanized PNPLA3 mice with the S453I variant to identify potential therapeutic targets