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No full textThe author submitted this entry in the 10-Word Story category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.Reflections on modernity
A Novel Squid Glaucoma microShunt for Controlled Release of Aqueous Humor
Get PDFThe 61st Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 31, 2023, 3-6 p.m., D1.600)BACKGROUND: Glaucoma is the second leading cause of blindness, affecting 80 million patients globally and 3 million in the US. Elevated intraocular pressure (IOP), caused by blockage of aqueous humor (AH) outflow from the anterior chamber, is an important risk factor. After medical treatments fail to control IOP, a glaucoma drainage device (GDD) is implanted. Current GDDs have major drawbacks: (1) large sizes requiring extensive surgical dissection, (2) uncontrolled AH release risking vision loss, and (3) prolonged inflammation/fibrosis leading to 50% failure rate at 5 years. To address this clinical need, we designed a new GDD, the Squid Glaucoma microShunt (SGS).
HYPOTHESIS: We hypothesize the SGS with a unique design based on the human aqueous-episcleral vein model will reduce IOP slowly and reliably, being an effective surgical glaucoma treatment.
METHODS: A 3D model of the SGS was rendered using computer-aided-design software SolidWorks. SGS is 90% smaller, designed to release AH in a slow, sprinkle-like fashion. To reduce inflammation, SGS will be coated with patented low-cost ultrananocrystalline diamond (UNCD) film exhibiting superb biocompatibility. A pair of patented micro forceps were designed for easy insertion, promoting 50% reduction in surgery time. An in-silico ANSYS fluidic simulation was designed to study fluid flow and pressure drop. To test the efficacy, UNCD was coated on an Ahmed® Shunt and inserted in a rabbit eye with the control eye having an uncoated shunt.
RESULTS: The ANSYS simulation showed that the SGS reduced IOP by 50% from 17 to 9 mmHg. At one year, the rabbit eye with UNCD coated Ahmed® shunt was quiet with low IOP, while the uncoated shunt failed within days due to intense inflammation/scarring. SGS and micro forceps prototypes were fabricated using Stratasys® 3D-printers. Our SGS would make early surgical intervention an option for glaucoma patients with presumably better outcomes, preventing blindness.Southwestern Medical Foundatio
Medicine in this day and age: addressing ageism in healthcare
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
Biomechanical Validation of Additively Manufactured Polymeric Femora
Get PDFThis poster was presented at the 25th UT Southwestern Department of Surgery Annual Research Forum in Dallas, Texas, on May 31, 2023.INTRODUCTION: Fourth generation composite bone models (Sawbones®) are biomechanically validated for testing loading conditions on normal human bone. However, for patients with altered anatomy, such as primary or metastatic bone neoplasms, accurate biomechanical models are unavailable. Rapid prototyping technologies, including additive manufacturing, can offer a solution if properly harnessed. The aim of this study was to develop and validate a 3-dimensional (3D) printed model of a normal human femur using polylactic acid (PLA) that can be adapted to variant anatomy.
METHODS: A literature review was conducted to identify the material properties of human femur bone. Standard dog-bone shaped tensile and compressive testing specimens were created with consistent printing parameters to evaluate the anisotropic mechanical properties of 3D printed PLA. After reviewing the differences in material properties, it was determined that incorporating geometric variation in the models was necessary to accurately replicate the biomechanical behavior of bone. A digital model of a normal human femur was obtained from Sawbones and prepared for 3D printing with wall thicknesses ranging from 0.4mm to 2.4mm and an infill density of 20%. A total of 12 models were printed, and standard three-point bending tests were performed, with measurements recorded to evaluate the mechanical response. The data obtained from the mechanical testing was analyzed to determine the starting point for future print parameter modification.
RESULTS: According to the literature review, values for material properties of the anatomic human femur are commonly reported as: flexural modulus of 11-20 gigapascals (GPa), flexural strength of 140-220 megapascals (MPa), ultimate tensile strength of 130 MPa, and ultimate compressive strength of 205 MPa. Testing of the dog-bone specimens yielded the following material properties: elastic modulus of 2.10 ± 0.03 GPa, ultimate tensile strength of 52.65 ± 1.90 MPa, and ultimate compressive strength of 57.70 ± 3.23 MPa. Testing of the 12 printed models produced a flexural modulus ranging from 7.46 to 18.35 GPa and a flexural strength of 342.4 to 832.7 MPa.
CONCLUSIONS: Our working hypothesis was that an optimized PLA-printed femoral diaphysis could model the biomechanical properties seen in actual human bone. The flexural modulus of the printed models replicated values reported in the literature for anatomic human femora, and the flexural strength above that seen in bone can be modulated down with geometric adjustments. These results serve as proof of principle that a 3D printed femur is a viable option for biomechanical studies. However, given the difference in material properties between human bone and PLA, geometric modifications such as changes to simulated cortical thickness and infill density are necessary to achieve model validity. Moving forward, further fine-tuning of the print parameters will lead to an optimized biomechanical response. The models will then be validated against Sawbones models. The full scope of this project includes adapting the geometry to patients with altered anatomy. Additional research will further expose the potential of 3D printing technology in both clinical and educational settings, such as preoperative planning, intraoperative reference, and the facilitation of resident and student education in orthopedics
Characterizing Interpersonal Perception in Adolescent Eating Disorders
Get PDFEating disorders (EDs) are associated with significant morbidity and mortality, and recovery is a challenging and often protracted process. Improved understanding of EDs, including identification and refinement of treatment and recovery targets, is necessary to improve intervention and treatment outcomes. Cognitive and interpersonal models of EDs propose interpersonal function as a risk and maintenance factor, and the adult ED literature documents challenges in self-concept and interpersonal function during illness that improve with recovery. Adolescence is a significant period for social development as well as ED onset and early intervention. Despite this, little research has prospectively examined interpersonal perception as a potential target in adolescents. This observational study examined baseline differences in self-referential thinking in adolescents with EDs (n = 29) compared to healthy control adolescents (n = 31) using the Internal, Personal, and Situational Attributions Questionnaire self-report and a Social Identity behavioral task. Self-attribution bias was also examined prospectively as it related to both time and clinical symptoms in 25 ED and 30 HC. When controlling for depression severity, the ED group had a more negative self-attribution bias than the HC group (p = .006). Additionally, the ED group exhibited less positive self (p < .001), social (p = .015), and socially reflected appraisals (p = .011) but no group differences for friend and friend reflected appraisals during the Social Identity task. After including depression as a covariate, however, the model was no longer significant, suggesting group differences in social appraisals may be mediated by depression. Additionally, there was no significant effect of clinical symptoms on self-attribution bias, although more severe clinical symptoms were significantly associated with lower valence indices for self, social, and socially reflected appraisals. Although significant group differences remained for self-attribution bias at follow up, there was no effect for time or group × time, nor was there a relationship between self-attribution bias change and clinical symptom change. Findings support valence in self-perception as a potential target in adolescent EDs. Future research should replicate results in larger samples and include longer follow-up duration to clarify the relationship between self-attribution bias and clinical status in adolescents
The Functional Roles for SWI/SNF Chromatin Remodeling Complexes in Physiology and Disease
Get PDFSequencing studies have implicated multiple subunits of SWI/SNF complexes in human neurodevelopmental and psychiatric disorders, as well as in cancers. Particularly haploinsufficiency of ARID1B, a SWI/SNF chromatin-remodeling subunit, has been implicated in short stature, autism spectrum disorder, intellectual disability, and corpus callosum agenesis. In addition, ARID1B is the most common cause of Coffin-Siris Syndrome, a developmental delay syndrome characterized by some of the above abnormalities. However, its role in pathologies is not well characterized due to absence of in vivo models. Therefore, in the first part of this thesis, we generated Arid1b heterozygous mice, which showed social behavior impairment, altered vocalization, anxiety-like behavior, neuroanatomical abnormalities, and growth impairment. In the brain, Arid1b haploinsufficiency resulted in changes in the expression of SWI/SNF-regulated genes implicated in neuropsychiatric disorders. A focus on reversible mechanisms identified insulin-like growth factor deficiency with inadequate compensation by Growth Hormone Releasing Hormone and Growth Hormone, underappreciated findings in ARID1B patients. Therapeutically, GH supplementation was able to correct growth retardation and muscle weakness. This model functionally validates the involvement of ARID1B in human disorders and allows mechanistic dissection of neurodevelopmental diseases linked to chromatin-remodeling.
ARID1A is a paralogous subunit that is commonly mutated in cancers and plays critical roles in liver regeneration. Chromatin remodeling mechanisms could be generally important for regeneration in other tissues. Since dynamic regulation of β-cell proliferation in pancreatic islets is poorly understood and better understanding could lead to therapeutic approaches for replenishing β-cell mass in type 1 and type 2 diabetes, in the second part of this thesis we focused on the role of ARID1A in β-cells. Arid1a is physiologically suppressed when β-cells proliferate during pregnancy or after pancreas resection. Whole-body Arid1a knockout mice were protected against streptozotocin induced diabetes. Cell-type and temporally specific genetic dissection showed that β-cell specific Arid1a deletion could potentiate β-cell regeneration in multiple contexts. Transcriptomic and epigenomic profiling of mutant islets revealed increased Neuregulin-ERBB-NR4A signaling. Functionally, chemical inhibition of ERBB or NR4A was able to block increased regeneration associated with Arid1a loss. Together, this work defined the role of ARID1A in β-cells and provided new insights into the molecular regulators of β-cell regeneration. Overall, we uncovered important roles of ARID1A and ARID1B-containing SWI/SNF complexes in physiological and disease states
Soothe
Get PDFThe author submitted this entry in the Fictional Short Story category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.Nature can heal many things that ails a human, mostly the emotional disruption that life can cause. I wanted to show how nature can heals but with a little bit of a supernatural element to it. Maybe, it will show more people that they need nature to heal them
Palliative Care for Refugees and Asylees: A Systematic Review and Single-Institution Analysis of Healthcare Utilization
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.BACKGROUND: Palliative care addresses physical, psychosocial, and spiritual dimensions of suffering. Palliative care may have significant impact for populations such as refugees and asylees, who flee conflict and persecution and may have a high burden of chronic and life-limiting illness.
OBJECTIVES: The goal of this systematic review was to synthesize existing observational studies on palliative care for refugees and asylees. Additionally, the goal of the accompanying single-institution review was to analyze healthcare access and utilization in a safety net refugee outreach clinic.
METHODS: A systematic review was undertaken using PRISMA guidelines. Six full-length articles were selected for review. National Consensus Project palliative care domains were utilized for thematic analysis. A retrospective chart review was undertaken for refugee patients establishing care between 2014-2016. Data was extracted on demographics, insurance status, and outpatient clinic and emergency department (ED) visits.
RESULTS: Articles selected for systematic review covered heterogeneous research methodology and refugee populations, with all investigators originating from high-income nations. Identified Challenges and Practices to palliative care encompassed all NCP domains, and Recommendations for palliative care for refugees and asylees encompassed all but the Ethical and Legal aspects of care. In our single-institution review, we found that most refugee patients were able to maintain healthcare insurance and attended follow-up primary care visits, with few relying on the ED for primary care.
CONCLUSIONS: Greater attention and funding should be allocated to lower-income nations for addressing refugee palliative care needs. Increased focus should be given to studying ethical, legal, and systemic barriers to care. Outpatient care in safety net hospitals may be an important means of addressing refugee and asylee palliative care in well-resourced settings
Genomic medicine in internal medicine practice
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
Gene Regulatory Networks in Striated Muscle Pathologies
Get PDFThe striated musculature, comprised of skeletal muscle and cardiac muscle tissues, is essential for vertebrate life. Skeletal muscles are composed of bundles of long and parallel multinucleated myofibers that constitute approximately 40% of the human body mass. The cardiac muscle is much smaller and consists of a branched network of short, mononucleated or binucleated cardiomyocytes that are connected by intercalated discs. Both these tissues partake in force generation through contractile units called sarcomeres to support movement, respiration (skeletal muscle), and to pump oxygenated blood throughout the body (cardiac muscle). Gene regulatory networks, the interactions between lineage or stage-determining transcription factors and the mRNAs they govern, tightly control cell function and striated tissue development and homeostasis. A disruption or change in these complex networks underlies most skeletal and cardiac muscle-related diseases. In this dissertation, we used transcriptomic and epigenomic approaches at single cell or bulk tissue resolution to provide a molecular framework for the function of TWIST2 in rhabdomyosarcoma pathogenesis as well as the mechanisms of heart remodeling and repair following myocardial infarction. In this process, we elucidated critical nodes in complex pathways that can be manipulated to derail the pathological process of FN-RMS or stimulate regeneration and repair in postnatal hearts