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Studies of the Molecular Features of Brd4-Nut and P300 That Contribute to Condensate Formation and Transcriptional Regulation
Get PDFAberrant formation of biomolecular condensates has been proposed to play a role in several cancers. The oncogenic fusion protein Brd4-Nut drives aberrant gene expression and forms condensates in Nut Carcinoma (NC). It has not been clear how these condensates form and whether they modulate gene expression. Here, I dissected the molecular features of Brd4-Nut and a histone acetyltransferase (HAT), p300, and analyzed their contribution to condensate formation and transcriptional changes. I determined that a minimal fragment of Nut (MIN) in fusion with Brd4 is necessary and sufficient for binding to p300, and for condensate formation. A Brd4-p300 fusion protein also forms condensates and drives a transcriptional profile similar to Brd4-Nut(MIN). The intrinsically disordered regions, transcription factor - binding domains, and HAT activity of p300 all collectively contribute to condensate formation. Conversely, only HAT activity appears to be necessary to mimic the transcriptional profile of cells expressing Brd4-Nut. My results suggest that interaction of Brd4-Nut with p300 is important for aberrant condensate formation, and that multiple, yet distinct, regions of p300 contribute to condensate formation and transcriptional regulation
Predisposition of COVID-19 patients to secondary infections: set in stone or subject to change?
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
The Effect of Antibiotic Prophylaxis on Infection Rates in Mohs Micrographic Surgery: A Single-institution Retrospective Study
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: Data and recommendations regarding antibiotic prophylaxis in dermatologic surgery vary in terms of effectiveness in preventing surgical site infection, prosthetic joint infection, infective endocarditis, and specifics regarding administration.
OBJECTIVE: The objective of this study is to describe the effect of antibiotic prophylaxis (AP) in Mohs micrographic surgery (MMS) on infective endocarditis, prosthetic joint infection, and surgical site infection.
METHODS: A single-institution retrospective cohort study of antibiotic use (pre-/intra-operative, post-operative or none) among 2,364 patient encounters treated with MMS was performed. Information regarding patient demographics, surgical site infection, prophylactic antibiotic administration (e.g. none, pre-/intraoperative loading dose, postoperative), type of repair, tumor type, surgery site, duration of patient stay, and other relevant covariates were collected. Inclusion criteria also included those who had at last one follow-up appointment or phone call with any provider after surgery. Bivariate logistic regression evaluated for associations between patient and operative characteristics, antibiotic use, and infectious complications.
RESULTS: 85.8% of patients received no AP, 10.0% received post-operative AP, and 4.1% received pre-/intra-operative AP. The overall surgical site infection (SSI) rate was 1.3%. SSI did not differ between patients who received pre-/intra-operative prophylaxis, post-operative prophylaxis or no antibiotics. One patient receiving pre-/intra-operative prophylaxis developed SSI. Repairs involving porcine xenografts and interpolation/pedicle flaps were associated with increased SSI. In addition, there were no patients who post-operatively experienced an infected joint or infective endocarditis.
CONCLUSION: There was no difference in rates of SSI when comparing MMS patients who received pre-/intra-operative, post-operative or no AP. There were no cases of infective endocarditis or infected prosthetic joints
Incidence and Predictors of a Difficult Airway in Lean vs. Obese Surgical Patients: A Large Prospective Cohort Study
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: With the high incidence of obesity rates, the determination of whether obese individuals are more difficult to intubate is of the utmost importance. This study aimed to determine the incidence of difficult intubation in obese vs lean patients in the general surgery population at a large tertiary, teaching hospital and assess obesity as a risk factor for difficult intubation. In addition, this study examined additional patient characteristics and anthropometric factors as independent predictors of difficult intubation. I hypothesize that obesity will not be a significant risk factor for difficult intubation. Instead factors such as age, higher Mallampati score, and male sex will be better predictors of difficult intubation.
METHODS: This prospective cohort observational study enrolled 4,003 patients undergoing general endotracheal anesthesia. Emergent cases, patients with a known or suspected difficult airway, and patients not expected to initially undergo direct laryngoscopy were excluded. Patients were stratified into two cohorts based on body mass index (BMI): a non-obese group (BMI <30 kg m-2) and an obese group (BMI ≥30 kg m-2). Intubation difficulty was determined using the Intubation Difficulty Scale (IDS).
RESULTS: The incidence of severely difficult intubation (IDS ≥ 5) was 5.9% in the obese cohort compared to 4.6% in the non-obese cohort which was not significant (p= 0.061). Controlling for other factors, obese patients were more likely to be difficult to intubate (odds ratio (OR), 1.438; 95% confidence interval (95% CI), [1.064, 1.943], p=0.001). In the analysis of additional patient characteristics and anthropometric values, age > 45 years (OR, 1.586; 95% CI, [1.064, 1.943], p<0.001), male sex (OR, 2.034; 95% CI, [1.532, 2.702], p<0.001), Mallampati score of 3-4 (OR, 2.441; 95% CI, [1.820, 3.273], p<0.001), neck circumference (OR, 1.096 per cm increase; 95% CI, [1.066, 1.128], p<0.001), thyromental distance (OR, 0.757 per cm increase; 95% CI, [0.691,0.830], p<0.001) and sternomental distance (OR, 0.923 per cm increase; 95% CI, [0.770, 0.874], p<0.001) were also significant. However, inter-incisor distance and waist circumference were not.
CONCLUSIONS: Obese patients are more likely to be difficult to intubate. However, male sex, age > 45 years, and a high Mallampati score are stronger predictors of difficult intubation compared to BMI. Therefore, while BMI still provides relevant information, BMI alone should not be used as a sole predictor of difficult intubation
Surprise
Get PDFThe author submitted this entry in the 10-Word Story category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.This piece was inspired by a few instances in my life. The most recent is waking up after a normal day and not able to take a step due to an ankle sprain. The most inspiring is after having elder friends that I spoke with them and hung out and finding out the next day that they passed in their sleep. These 10 simple words sums up that realization. From an injury or just life itself and the realization that someone else's has ended outside of anyone's knowledge
Assessing Approach Motivation in Depressed Individuals with a History of Concussion
Get PDFPages viii-xiii are misnumbered as pages v-x, and pages 41-58 are misnumbered as pages 1-18.Depression is the leading cause of disability worldwide. Anhedonia, a core symptom of depression, has been described as a lack of pleasure or interest, though it is a much more complex process than simply lack of pleasure. Anhedonia is made up of anticipation, motivation, enjoyment, and learning related to rewards. When an individual's motivation is impaired, reward perception is blunted as the drive to work for it is reduced. This "approach motivation" is generally subserved by the ventral striatum and orbitofrontal cortex, two areas which can be affected in a variety of neurologic conditions, including traumatic brain injury, as these subcortical structures can be affected by pathophysiological sequalae of trauma. To explore this concept, we examined data from a large ongoing study of adult depression (Dallas 2K). A total of 110 participants with depression with (n=40) and without a history (n=70) of self-reported concussion were tested on a measure of approach motivation, the Energy Expenditure for Rewards Task (EEfRT). We also analyzed depression symptom severity and the relationship between anhedonia severity to approach motivation on the EEfRT. Results revealed no significant differences between depressed adults with and without a history of concussion on approach motivation. Exploratory analyses revealed differences between high and low depression severity groups, such that high depression severity participants were less likely to select low probability/high reward tasks, but this was irrespective of concussion history. Though the main study results were nonsignificant, exploratory analyses present an opportunity for future direction of studies related to approach motivation and cognition in co-morbid depression and concussion
Me, Myself, and AI
Get PDFThe author submitted this entry in the AI Literature category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.The growing reliance on AI for diagnosis, prescription, and even patient interaction intrigues me. This piece is a reflection on the role I expect artificial intelligence to play in the future of medicine, and how I would like to adapt to it
A Blind Perspective
Get PDFThe author submitted this entry in the 10-Word Story category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.Reflections on perspective
Death's Intimate Familiarity
No full textThe author submitted this entry in the Creative Non-Fiction category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.This work received a First Place Award in the "Creative Non-Fiction" category from all literary works submitted in the 2023 On My Own Time show.I am a 20-year veteran of the Emergency room including about 5 years in a Pediatric ER. Also, I am an Army veteran (army recon, not medical). I have seen more death than any one person should but through it all I have made an intentional decision to see the world in a positive lens. There is so much sorrow but if you look, so much beauty and wonderment
61st Annual Medical Student Research Forum
Get PDFThe 61st Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 31, 2023, 3-6 p.m., D1.600)This 148-page booklet is the proceedings of the 61st Annual Medical Student Research Forum and includes a list of oral presentations, a table of contents to the abstracts, and the abstracts divided into three categories: Basic Research and Disease Models; Clinical Research; and Quality Improvement, Global Health, Medical Education, Community Health, and Research Design.Southwestern Medical Foundatio