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Deep brain stimulation enhances control and restores valued personality characteristics
Get PDFTuesday, November 8, 2022; noon to 1 p.m. (Central Time); Room D1.502 or via Zoom. "Deep Brain Stimulation Enhances Control and Restores Valued Personality Characteristics". Cynthia S. Kubu, Ph.D., ABPP-CN, Professor of Neurology and Vice Dean for Faculty Case Western Reserve University School of Medicine, Cleveland Clinic.Questions related to what constitutes personality, and how those conceptualizations interface with notions of self, identity, and autonomy, have fascinated psychologists, philosophers, and ethicists for hundreds of years. Since 2008, several studies have asserted that deep brain stimulation (DBS) results in patients’ loss of control, particularly related to undesired personality changes. Inherent in this argument is the thesis that DBS negatively impacts patients’ identity, autonomy, and personality. Our lab has relied on empirical methods to examine questions related to control in patients who undergo DBS to treat motor symptoms. Our data refute the claims that DBS results in a loss of control. We rely on the American philosophical tradition of pragmatism to conduct our work, particularly the emphasis on different ways of knowing, including the perspectives of various disciplines as well as different stakeholders in understanding, studying, and ultimately implementing practices based on good data.UT Southwestern--Program in Ethic
Assessment of Circularized HPV16 E7 RNA, GLUT1, and PD-L1 in Anal Squamous Cell Carcinoma
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: Anal squamous cell carcinoma (ASCC) is a rare, deadly malignancy caused by high-risk human papillomaviruses in up to 90% of cases and continues to be treated by cytotoxic therapy established 40 years ago. There is a dearth of reliable biomarkers for ASCC. The prognostic implication of programmed death-ligand 1 (PD-L1) expression remains controversial while other biomarkers, like glucose-1-transporter (GLUT1) expression levels, have not been examined in the setting of ASCC. More recently, covalently closed circular RNAs has been (circRNA) expression has been shown to be widespread in cancers, and circRNAs have been proposed to be potential biomarkers. In previous studies, we discovered a novel circular E7 RNA expressed by HPV16 (circE7), which has not been assessed as a potential biomarker in any diseases.
OBJECTIVE: We hypothesize that human papillomavirus infection status, increased GLUT-1 expression, increased PD-L1 expression, and HPV E7 RNA expression will serve as biomarkers for higher mortality in patients with anal squamous cell carcinoma.
METHODS: A retrospective, translational case series was conducted on twenty-two subjects to analyze PD-L1, GLUT1, HPV-ISH, and HPV circE7 in relation to the clinical features and overall survival of patients with anal squamous cell carcinoma. To supplement understanding of the HPV circE7 biomarker, bioinformatic analyses of RNA-Seq data from the Cancer Genome Atlas was performed on 875 subjects with HPV-driven head and neck cancer and cervical cancer.
RESULTS: Improved overall survival could be predicted histologically by pure basaloid architecture (p=0.013), PD-L1 expression (p=0.08), HPV-ISH positivity (p<0.001), but not GLUT1 expression. Quantitative RT-PCR of archived tumors revealed that high levels of circE7 in ASCC were predictive of improved overall survival (p=0.023). Bioinformatic analyses suggested that the presence of high amounts of circE7 correlated to improved survival in 875 subjects (p=0.074).
CONCLUSION: Glut-1 overexpression was ubiquitous among all anal squamous cell carcinoma cases but was not predictive of survival. This study adds to the growing evidence of PD-L1 expression correlation to improved survival in ASCC. CircE7 levels correlate with improved survival in anal squamous cell carcinoma but larger, prospective studies are necessary to confirm the potential role of circE7 as a biomarker
Underutilization of Palliative Care in Metastatic Foregut Cancer Patients Is Associated with Socioeconomic Disparities
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: Metastatic foregut cancers are frequently associated with debilitating symptoms that significantly impact patient's quality of life. Palliative care aims to mitigate disease-, psychosocial- and treatment-related effects. Despite numerous reported benefits and current guidelines and recommendations, palliative care remains heavily underutilized in patients with metastatic cancers.
OBJECTIVE: Our aim was to determine the rate of palliative care utilization among patients with metastatic foregut neoplasms and determine the socioeconomic factors associated with receipt of palliative care.
METHODS: A retrospective review of the National Cancer Database (NCDB) was conducted to identify patients diagnosed with metastatic foregut cancers between 2004-2013. The NCDB captures over 70% of all incident cancer cases in the United States. We identified patients with stage IV gastric, pancreatic, biliary, gallbladder and esophageal adenocarcinoma. Receipt of PC as defined by the NCDB participant use file was correlated to demographic and clinicopathologic factors. PC treatment included surgery, radiation, systemic therapy, and pain management to alleviate symptoms. Logistic regression was performed to assess the impact of factors on the likelihood of receiving PC. Overall survival was estimated using the Kaplan-Meier method and compared using log-rank tests.
RESULTS: Palliative care utilization rates increased among all groups over time (12.3% 2004-2006 vs. 14.7% 2007-2010 vs. 16.4% 2011-2013 for all cancers). Female sex, Medicaid, median income < USD 46,000/year, higher education level, higher Charlson/Deyo Score, and pancreatic or biliary cancers were associated with increased likelihood of palliative care interventions. Additionally, patients treated at an academic center or integrated network cancer program were more likely to receive palliative care than patients treated in the community setting. When receipt of palliative care was stratified by race, Hispanics were significantly less likely to have undergone palliative interventions compared to non-Hispanic Whites (OR 0.70, 95% CI 0.66-0.73). Patients with Medicare or private insurance were less likely to receive palliative care than uninsured patients (OR 0.92, 95% CI 0.87-0.97 and 0.81, 95% CI 0.77-0.89, respectively)
CONCLUSION: Although PC use has increased over time, it remains significantly underutilized in MFC. Disparities exist in receipt of PC with regards to demographic and socioeconomic factors such as age, race, gender, insurance status, education, comorbidities and year of diagnosis. These identified factors can serve as targeted interventions aimed at increasing palliative care utilization. Additional research is necessary to better optimize PC use in metastatic cancers of the foregut and mitigate potential disparities
Insight into Microtubule Catastrophe and Growth
Get PDFPages ii-xi are misnumbered as pages i-x.Microtubules are hollow cylindrical polymers of αβ-tubulin that have essential roles segregating chromosomes during cell division, organizing the cytoplasm, establishing cellular polarity, and more. These fundamental activities depend critically on dynamic instability, the stochastic switching of microtubules between phases of growth and rapid shrinking. Dynamic instability is itself a consequence of αβ-tubulin GTPase activity and how it affects interactions between αβ-tubulin in the lattice and at the microtubule end. Although predictive molecular understanding of catastrophe remains elusive, the broad outlines of an understanding have been established. Unpolymerized, GTP-bound αβ-tubulin subunits readily associate at the growing tips of the MTs. Once they are incorporated into the lattice, αβ-tubulin GTPase activity is accelerated. The assembly dependence of GTPase activity results in a "stabilizing cap" of GTP-bound αβ-tubulin near the ends of the growing microtubules. Loss of this stabilizing cap triggers catastrophe, the switch from growth to rapid shrinking, because it exposes the more labile GDP-bound microtubule lattice. And, regaining this GTP cap results in microtubule rescue, the switch from shrinking to growing phase. In Chapter 1, I discuss literature background for microtubule dynamics. In Chapter 2, I present a study in which I explored the molecular mechanism behind microtubule catastrophe using computer simulations. By incorporating various candidates for "missing biochemistry" into the computational models, I discovered that lateral long-range interdimer interactions are crucial in correctly predicting catastrophe frequency as a function of the soluble tubulin concentration. In Chapter 3, I discuss a study that directly measures the αβ-tubulin association and dissociation at the microtubule end. We found that the kinetic on-rate of tubulin dimer to a growing microtubule end may be much smaller than previously thought. Next, in chapter 4, I present studies that explore various factors that affect microtubule shrinking and rescue. Finally, in chapter 5, I will summarize my work on these projects and discuss future directions and preliminary results looking to better understand microtubule dynamics
UT Southwestern Journal of Pediatrics 1 (1)
Get PDFVolume 1(1): June 3, 2022Dear Readers,
We present to you the inaugural issue of the University of Texas Southwestern Pediatric Residency Program's Journal of Pediatrics. It represents some of our contemporary efforts to learn with and from our colleagues, and our desire to share this with a broader audience. It's not a coincidence that we are launching this journal in the context of the COVID-19 pandemic. As seems true for many of our experiences related to the challenges of the pandemic, perhaps individual isolation and societal grief have made us even more committed to remaining connected with others. This journal has three main sections: peer-reviewed case reports from our residents, posters presented by our senior residents at our 10th annual residency scholarly projects conference, and humanities creations from our current cohort of resident colleagues. We aim to use this journal as one enduring means to share highlights of our pediatric residents' educational experiences - with our Residency Program, our Department and the larger pediatric community. It is a privilege and a joy to share with you some of the stories of those whom we seek to serve, the scholarship of our graduating residents, and the perspectives and artwork of our peers. We hope you find inspiration within.UT Southwestern Department of PediatricsEditorial Board - page 2
Letter From The Editors - page 6
Chief Resident Time Capsule - page 7
Academic Half Day - page 7
Advocacy - page 7
Board Preparation - page 7
Cardiology - page 7
Career Preparation - page 7
Education Liaisons/Inpatient Education - page 8
Electives - page 8
Emergency Medicine - page 8
House Cup - page 8
Intern Conference - page 8
M&M - page 8
Moonlighting - page 8
Nephrology - page 8
PICU - page 8
Recruitment - page 9
Research - page 9
Simulation - page 9
Sick Call (SC/BU) / Jeopardy - page 9
Surge - page 10
Wellness - page 10
Case reports - page 11
A Case of Persistent Rectal Bleeding in a 16 Month Old Female - page 12
Rare secondary malignancy mimicking osteomyelitis - page 15
Prolonged Fever in a Middle School Child - page 18
Infection or exposure?: A complex presentation of vaping induced lung injury in an adolescent female - page 21
Case Report: Complications of Thyroid Storm in a 16 year old Female - page 26
10th Annual Scholarly Symposia Posters - page 30
Platform Presentation: Elena Chen MD - Impact of Simulation Curriculum on Pediatric Resident Comfort with High Acuity Clinical Situations and Crisis Management Skills - page 31
Platform Presentation: Justin Williams MD - Clostridiodes difficile colonization in patients admitted to a gastroenterology inpatient service - page 33
Best Academic Presentation: Elliott Huang MD MPH - Clinical Characteristics of Pediatric Patients with Rhabdomyolysis: a 10 Year Retrospective Review - page 35
Best Academic Presentation: Zachary Stone MD - An Introduction to Healthcare Program for Local High School Students - page 37
Averi Wilson MD - Development, Implementation, and Evaluation of a Resident Telemedicine Curriculum - page 39
Bradley Graves MD - Tracheostomy Outcomes in a Cohort of Children in a Primary Care Medical Home For Children in Foster Care - page 41
Jonathan Fletcher MD PhD - Secondary Histiocytic Sarcoma in Pediatric Leukemia - page 43
Lydia Sandy MD - Leveraging the TriNetX database to explore the association between obesity and dyspnea in pediatric patients - page 45
Alyna Garza MD - Utility of Infographics for presenting AAP recommendations to pediatric resident - page 47
Amisha Patel MD - Team KiPOW (Kid Power) Texas - page 49
Cristina Saez MD - Culturally Sensitive Care for Latino Immigrant Populations: An Introductory Curriculum for Pediatric Residents - page 51
Ealing Mondragon MD - Comparing Efficacy of Self-Guided vs. Synchronous First-Time Seizure Education for Residents - page 53
Annette Ville, MD, Kelly Parsons, MD, Katie Dolak, MD - Medical Student to Pediatrician: A Focus on Telemedicine and Primary Care - page 55
Shivani Misra MD MPH - Development of a Trauma-Informed Parent Education Session - page 57
Rebecca Duron MD MSPH - Implementation of Screening for Adverse Childhood Experiences in Med-Peds Clinic - page 59
Chelsea Burroughs MD - Determining Parental Core Values Regarding Complex Decision Making in the Neonatal Intensive Care Unit - page 61
Hannah Justice MD - Barriers to mental health care utilization in a large pediatric residency program - page 63
Matthew Hibbs MD - Are You All "Write": A pediatrics-centric narrative medicine curriculum to reduce resident physician burnout - page 65
Michael Hook MD - Pediatric Multiple Magnet Ingestion: A Single Center Experience - page 67
Sonia Allouch MD - Improving HPV vaccination rates in CHMG and AYA clinic - page 69
Swetha Kotamraju MD - Improving Dietician Follow up of Enterally Fed Patients in an Outpatient Subspecialty Clinic - page 71
Donovan Berens MD - Improving Screening for Non-Alcoholic Fatty Liver Disease in a Primary Care Setting - page 73
Medical Humanities - page 76
Medical Spanish: Reflection Essay - page 77
Stories and lessons of Latin women growing up in America and how they shaped who they are - page 78
The Intern Account: A Post-Concussive Rollercoaster - page 79 / The Intern Account IIa: Ramadan and Medicine - page 82
Mi Mejor Amigo (My Best Friend) - page 85
UTSW Pediatric Residency "The Giving Tree" painting - donated by the classes of 2020-2023 to the pediatric patients we cared for during the COVID-19 pandemic - page 9
Characterization of Host and Microbiota Derived Signals that Regulate the Locus of Enterocyte Effacement of EHEC
Get PDFHumans are populated by an extensive community of microorganisms, primarily in organs such as the skin, mucosal membranes in the mouth, reproductive organs, and the gut. This complex community, termed the microbiota, is in part comprised of bacteria, many of which have intimate associations with their hosts to promote physiological homeostasis. These organisms, commonly termed commensal bacteria, have a rich and long history with their human hosts and accomplish important functions such as providing the host with nutrients, developing the immune system, and preventing colonization by pathogenic organisms in a process known as colonization resistance. These functions are especially apparent within the gastrointestinal (GI) tract, which contains the richest and most densely populated community of microbes in the body. Healthy gut function relies on the proper structure and balance of this microbial community. Disruption of the community, termed dysbiosis, has been associated with a plethora of diseases such as increased susceptibility to GI infections, neurological disorders, intestinal inflammation, and cancer progression. Dysbiosis is most commonly caused by pharmacological interventions with antibiotics or infection with a GI pathogen.
The microbiota is regarded as a barrier against intestinal pathogens, partly due to intense competition for a limited supply of nutrients and space. This suggests that GI pathogens have evolved mechanisms to overcome colonization resistance and outcompete the resident microbiota for resources within the GI tract. Microbiota and host-derived metabolites have a significant impact on the abilities of GI pathogens to successfully establish intestinal infection and the subsequent development of disease. However, the precise mechanism by which microbiota or host metabolites affect the pathogenesis of GI pathogens is not well understood. Many of these nutrients, whether host-, diet-, or microbiota-derived, serve as chemical cues for incoming pathogens. These signals are used by pathogens to gauge resource availability, microbiota composition, host physiology, and location within the intestines to properly deploy virulence strategies that allow for colonization. Microbiota-derived small molecules include toxins, antimicrobials, oligopeptides, hormones, and products of microbial metabolism of host-derived and dietary molecules. Pathogens can directly sense many of these host- and microbiota-derived small molecules, which in turn can regulate their virulence mechanisms. Taken together, developing therapeutics that target the signaling pathways that control virulence-associated functions in pathogens represent an attractive alternative or secondary strategy to tackle bacterial infections.
In a previous study, our group conducted a candidate-based screen of 372 independent mutants to look for novel regulators of the T3SS [1]. The candidates of this screen consisted primarily of transcription factors, two-component regulatory systems, anti-terminators and anti-toxins. This work generated a great number of hits that potentially regulate the T3SS of EHEC. Our work sought to characterize novel signaling pathways that directly affect the virulence of enterohemorrhagic Escherichia coli (EHEC) through characterization of some of the hits of said screen in particular the transcriptional regulators ExuR and FadR. Understanding of these signaling pathway could lead us to develop novel strategies to drive down the virulence of enteric pathogens and improve colonization resistance as an alternative approach to control bacterial infections.
Here, we found that EHEC senses and utilizes galacturonic-acid (GalA) as a nutrient during infection and moonlights as a signal to downregulate the expression of virulence associated genes. Furthermore, we demonstrated that a pectin-rich diet, which is a source of GalA, increased mice tolerance towards a Citrobacter rodentium infection, a surrogate mice model for EHEC infection. AE pathogens like EHEC and C. rodentium thrive in an inflamed environment. During the onset phase of inflammation, the host-derived polyunsaturated omega-6 long-chain fatty acid (LCFA), arachidonic acid (AA) becomes elevated to produce endogenous lipid signaling molecules like prostaglandins and leukotrienes that act as inducers of inflammation. EHEC can sense long-chain fatty acids through the FadR response regulator. We found that AA is processed by EHEC using canonical LCFA signaling pathways involving the FadL LCFA transporter, the FadD acyl-CoA synthase and the FadR transcriptional regulator.
In conclusion, we characterized the signaling pathways that mediate the sensing of galacturonic-acid and arachidonic-acid. We demonstrated that a diet high in pectin can effectively be used to control an infection by C. rodentium by effectively modulating the levels of GalA and affecting virulence in an ExuR dependent manner. We also showed that EHEC is capable of sensing a host produced long chain fatty acid like arachidonic acid to regulate its virulence. These studies highlight the complexity that underlies regulation of the locus of enterocyte effacement and perhaps will serve as a starting point for the development of new strategies to control enteric infections
Approach to interstitial lung 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
Simple Measures to Reduce Opioid Prescriptions Following Pediatric Spinal Fusion Surgery: A Multidisciplinary Quality Improvement Project
Get PDFThe 60th Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, February 1, 2022, 3-6 p.m., Microsoft Teams)BACKGROUND: The opioid epidemic is one of the biggest challenges facing modern healthcare. Among the adolescent and young adult populations opioid overdose is one of the leading causes of death.
LOCAL PROBLEM: Within pediatric orthopaedics, spinal fusion is a common procedure making up 7% of the surgical volume at our institution. Spinal fusion also has high postoperative opioid prescribing rates. Review of baseline data showed that there was wide variability in prescribing habits. The goal of this quality initiative was to reduce and standardize post-operative opioid prescribing following spinal fusion procedures.
METHODS: Data, including opiate-prescribing habits and a patient survey to assess patient and parent satisfaction with pain control, was collected retrospectively in the pre-intervention phase for 99 consecutive Adolescent and Juvenile Idiopathic Scoliosis patients undergoing spinal fusion surgery. This was followed with 2 PDSA cycles following implementation of a new protocol during which prospective surveys were administered to a total of 273 patients. Physician prescribing data was collected for 150 patients during the sustain phase.
INTERVENTIONS: A multi-pronged approached was utilized consisting of the following aspects: 1) Instruction to orthopaedic trainees to limit opioid prescriptions to 45 and 40 for PDSA cycles 1 and 2, respectively. 2) A pharmacy-led education program with an opioid tapering handout given to families and encouragement of usage of non-opioid pain control. 3) A call to the prescribing physician from pharmacy if the prescribed dosage was greater than the maximum allowed.
RESULTS: There was a significant reduction in opioid prescriptions from a preintervention mean of 48.5 doses to a PDSA 1 mean of 39.0, PDSA 2 mean of 37.5, and a sustain phase mean of 36.4 (p=0.000). This represented an estimated reduction of 22.8% over the course of the study. During this time, there was no significant change in patient and parent reported postoperative pain.
CONCLUSIONS: Through simple measures, our institution was able to significantly reduce total opioid prescriptions following spinal fusion surgeries while maintaining good pain control.Southwestern Medical Foundatio
Risk Factors for Surgical Site Infection in Distal Radius Fracture Surgery
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.Page ii is misnumbered as page iii.The student submitted 2 separate documents as part of his research project, and this is part 1 of 2. The second part has been uploaded to a separate record, which can be viewed at the Related URI listed in this record.PURPOSE: Surgical site infections (SSI) after distal radius surgery can introduce substantial morbidity and additional direct and indirect costs. The clearest risk factors for SSI are the use of externalized Kirschner wires (K-wires) or external fixation (ex-fix). The roles of other potential risk factors such as open injuries, diabetes mellitus, and tobacco use are less clear. The purpose of this study was to identify independent risk factors for SSI in distal radius surgery.
METHODS: A retrospective study of 541 operative distal radius fractures over a 5-year period was performed. Potential risk factors for infection included surgery duration, externalized K-wires or ex-fix, diabetes mellitus, uncontrolled diabetes defined as a HgBA1c >7 documented within a 90-day perioperative period, open fracture, tobacco use, osteoporosis, gender, and age. A screening bivariate logistic regression was performed, followed by a multiple logistic regression of the selected independent variables, with SSI as the dependent variable. A p-value of <0.05 was considered statistically significant.
RESULTS: Twenty fractures (3.7%) were complicated by post-operative SSI, and 521 (96.3%) were not. Uncontrolled diabetes with HgA1c >7 (OR = 7.83, p=0.002), the presence of an ex-fix or k-wires (OR =3.73, p=0.007), and tobacco use (OR=3.79, p=0.007) were significant independent predictors of SSI. Of note, while uncontrolled diabetes was an independent risk factor, the diagnosis of diabetes alone was not.
CONCLUSIONS: Previously identified risk factors for SSI after distal radius surgery including the presence of externalized K-wires or ex-fix were confirmed in this study. Additionally, this study demonstrates that tobacco use and uncontrolled diabetes (HgA1c >7) are both independent risks factors for SSI. Notably, the presence of diabetes alone was not an independent risk factor, highlighting the importance of glycemic control.
LEVEL OF EVIDENCE: Level II