Texas Digital Library
UT Southwestern Medical Center Institutional Repository (University of Texas)Not a member yet
10274 research outputs found
Sort by
What makes the use of biospecimens (and other health data) ethical?: let the public speak
Get PDFTuesday, February 8, 2022; noon to 1 p.m. (Central Time); via Zoom. "What Makes the Use of Biospecimens (and Other Health Data) Ethical? Let the Public Speak." Raymond G. De Vries, Ph.D., Professor Emeritus, Center for Bioethics and Social Sciences in Medicine, University of Michigan Medical School.The creation of sustainable and ethical policies in health care and the life sciences requires soliciting and incorporating the attitudes and opinions of the "public," a difficult task that is even more challenging in a political polarized society and when the policies in question are explicitly normative. Using research on public attitudes about the use of their biospecimens and health data, we will look at various methods used to solicit those attitudes and consider the strengths and limitations of those approaches. We will reflect on the value of empirical data for resolving normative questions (in other words, the age-old is/ought problem) and think together about better ways to incorporate the opinions of the demos in health policy.UT Southwestern--Program in Ethic
BDNF-Producing B Cells Mediate Plasticity in the Recovering Brain After Stroke
No full textNeuronal networks require significant neurotrophic support for functional plasticity after stroke, but the delivery of neurotrophins has failed thus far in clinical trials. Therefore, identifying endogenous mechanisms that could enhance neurotrophic support in the recovering brain after stroke is essential. B cells, a lymphocyte known to infiltrate the post-stroke brain, possess the ability to produce neurotrophins, including brain-derived neurotrophic factor (BDNF). Depleting B cells after stroke results in motor and cognitive deficits that are mediated by specific brain regions (e.g., hippocampus) outside the initial infarct. We propose that B cells migrate to specific brain regions after stroke and respond to local signals that enhance their neurotrophic capacities to promote neuroplasticity. To investigate whether B cells are a potential source of endogenous BDNF support after stroke, we must identify 1.) the spatial distribution of B cells within the post-stroke brain, 2.) the type of neurotrophic support B cells provide to ischemic-injured neurons and 3.) the impact that the post-stroke microenvironment exerts on the neurotrophic capacity of B cells. Using whole brain microscopy, we discovered that B cells migrate to specific remote brain regions areas outside of the initial infarct that regulate motor and cognitive function after stroke. To understand how B cells support ischemic-injured neurons, we used ex vivo electrophysiology and in vitro models of ischemic injury to assess functional and structural neuroplasticity in the presence or absence of B cells. We discovered that B cells support synaptic transmission in the dentate gyrus region of the hippocampus after stroke and through the production of BDNF, B cells protect against the ischemic-induced loss of neurons and neuronal dendrites. After stroke, neuronal BDNF production is dependent on glutamate-induced activity of the N-methyl-D-aspartate receptor (NMDAR) downstream of the GluN2A subunit. Given that B cells also express NMDARs, we investigated whether glutamate can similarly upregulate BDNF in B cells downstream of their NMDARs. Using microscopy, flow cytometry and qPCR, we discovered that stroke and glutamate differentially regulate B cell gene and surface expression of GluN2A. Additionally, both mouse and human B cells elicit a functional response to glutamate and can induce autocrine BDNF signaling. Collectively, the data presented in this thesis are the first to demonstrate a glutamate-induced neurotrophic role for B cells in the ischemic brain. Understanding the mechanisms by which neuroinflammation supports neuroplasticity after stroke enables the development of immune-based therapeutics that harness endogenous neurotrophic support from B cells to ameliorate pathology
Childhood Wonder
No full textThis poem examines a childhood memory, using the wonder and compassion of the eyes of the child tainted with adulthood
Reflections on a Single Institution Cochlear Implant Experience
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.OBJECTIVE: To utilize cochlear implant (CI) outcomes to further explore health disparities, hearing preservation (HP) surgery, and standardization of pre- and post-operative CI assessment, with the goal of predicting and improving CI outcomes, including quality of life.
STUDY DESIGN: Retrospective chart review of adult patients who underwent CI evaluation and surgery at a single institution between 2009 and 2018.
MAIN OUTCOME MEASURES: Improvement in open sentence testing postoperatively, according to patient marital status, race, and gender, as well as HP status.
RESULTS: Post-operative performance: Of the 402 total patients who underwent CI during the study period, 372 were followed and programmed at the institution. A total of 87% of these patients achieved "good performance" with their CI, based upon an improvement in post-operative open sentence testing ≥10%. Patient demographics, including gender, age, marital status, and race did not significantly affect whether a patient achieved higher post-operative performance levels. Unmarried patients saw poorer outcomes, but this did not reach significance (37.5% vs 24.3%, p = 0.2123).
HEARING PRESERVATION: HP surgery evolved during the study period, with modern "soft surgery" technique defined by perioperative steroids, round window cochleostomy, and atraumatic CI insertion. A slight majority of HP surgical patients maintained low frequency hearing postoperatively (54.2%). However, documentation of preserved hearing was limited, with only 53.7% of patients with recorded unaided audiograms. Analyzing speech perception outcomes, HP candidates, and patients who underwent "soft surgery," did not demonstrate significantly larger improvements with their post-operative open sentence testing when compared to patients who underwent standard CI, and were concurrently not HP candidates, during the study period (overall improvement: 41% vs 53% respectively, p = 0.10). Additionally, non-white hearing preservation candidates were less likely to retain low frequency hearing post-operatively, but this did not reach significance in the study population (22.2% vs 8.5%, p=0.0992). However, HP surgery, and overall CI surgery outcomes assessment was limited by lack of standardized documentation.
CONCLUSIONS: Unmarried patients and non-white patients continue to warrant special attention post-operatively to ensure equability in CI. HP surgery has evolved over the past decade. All, patients, should also have their quality of life evaluated, with standard assessment through open sentence testing failing to demonstrate the added benefit of HP, and likely the overall benefit of any CI. There continues to be a need for standardization in CI evaluation, documentation, and follow-up to allow for larger outcomes based research.
IRB: STU 032018-085
PROFESSIONAL PRACTICE GAP AND EDUCATIONAL NEED: The field of CI is in need of large outcome based studies to better predict which patient factors, including demographics and HP status, may predict CI success.
DESIRED RESULT: Systematic review of a decade of cochlear implantation outcomes in order to identify areas in which improvement will result in increased ability to assess outcomes, and augmented cochlear implant success leading to improved CI patient quality of life
The pathogenetic revolution in immune mediated inflammatory diseases
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
Seeking Companionship
No full textI love cats, and imagined just for fun what might a cat's personal ad look like? Or, could be it a human seeking a companion
Examining the Feasibility of a Resilience Mental Health Application in Adolescents
Get PDFBACKGROUND: Resilience is defined as the ability to rely on internal characteristics and external strengths to adapt in the face of adverse events. While universal resilience-enhancing programs are effective for adolescents, there is still a need for interventions that are easily accessible and specific to the individual. Phone applications are easy to use, tailored to the individual, and have shown positive effects for mental health outcomes. This study will determine if a resilience application is feasible and acceptable for adolescents, evaluating whether or not short-term use leads to changes in resilience.
METHODS: For Study 1, Phase 1, individual interviews and focus groups were conducted with adolescents, parents, teachers, and clinicians to discuss possible incentives for using a mental health application, the benefits of using an application, and what concerns would arise from using an application. For Study 1, Phase 2, individual interviews and focus groups were conducted with adolescents, parents, teachers, and clinicians to gather feedback about the resilience application prototype. For Study 2, 40 adolescents used the application for 30 days to gather more information about feasibility, acceptability, and if there were significant positive changes with resilience and other secondary mental health outcomes.
RESULTS: Multiple themes were identified through Study 1 individual interviews and focus groups, including application content, features, engagement, benefits, concerns, and improvement. Study 1, Phase 2 adolescents and adults reported the prototype was feasible and acceptable through the Computer System Usability Questionnaire (M = 6.30, SD = 1.03) and Mobile Application Rating Scale (M = 4.08, SD = 0.61). For Study 2, there were no significant differences for resilience and mental health outcomes after using the application for 30 days. Users appeared to prefer the depression module and survey sections, which provided mental health feedback.
CONCLUSION: Qualitative and quantitative data provide evidence that youth are interested in a resilience mental health application and found the current prototype to be feasible. Although there were no significant mental health changes for Study 2 users, clinical implications and future directions are discussed for mental health application research
Between a Block, Fifty Hot Wheels and a Hard Place
Get PDFThis work received a Third Place Award in the "Creative Non-Fiction" category from all literary works submitted in the 2022 On My Own Time show.Reflections on raising 5 sons
Neuropsychological Functioning in Aging National Football League Retirees
Get PDFConcussive and sub-concussive head impacts sustained over a National Football League (NFL) career have been proposed to increase risk for later cognitive impairment. However, research is generally limited on the neuropsychological functioning among NFL retirees, and no studies to date have investigated the cognitive performance of NFL retirees over time. Study One was a critical review of research on neuropsychological functioning among NFL retirees. Findings were mixed, but studies suggested some NFL retirees have lower verbal memory, confrontation naming, and executive functioning abilities compared to control groups. Investigations of dose-response relationships between cognition and head-injury exposure also generated mixed findings which may be related to small samples, sampling bias, small effect sizes, and the measurement of different head-injury exposure variables. Study Two was a prospective cohort design investigating neuropsychological functioning and head-injury exposure in NFL retirees aged 50 and up. Retirees underwent baseline (N = 53) and follow-up (N = 29) comprehensive neuropsychological evaluations. Cognitively normal retirees (n = 26) were age, education, and IQ-matched to healthy controls (n = 26). Retirees diagnosed with MCI or dementia (n = 27) were matched as closely as possible to a clinical sample of patients with MCI and dementia by age, education, and diagnosis (n = 22). Independent samples t-tests and repeated measures ANCOVAs were used to evaluate neuropsychological scores between groups. Pearson correlations, partial correlations, and quadratic regressions were used to examine relationships between head-injury exposure and neuropsychological scores. Head-injury exposure variables included concussions, number of concussions with loss of consciousness, years playing professionally, games played, games started, and age beginning tackle football. Overall, NFL retirees did not significantly differ on the majority of measures at baseline or on any measures over time compared to their respective control groups. Furthermore, the vast majority of neuropsychological scores were not significantly related to head-injury exposure, regardless of cognitive diagnosis. In totality, findings suggest that NFL retirees do not have lower cognitive functioning compare to non-athlete controls later in life, and that head-injury exposure obtained over an NFL career is not related to cognitive functioning later-in-life
Neural Mechanisms and Behaviors in Models of Conditional Nprl2 Loss
Get PDFThe file named "DENTEL-PRIMARY-2022-1.pdf" is the primary dissertation file. Two (2) supplemental video files are also available and may be viewed individually.The amino acid sensitive arm of mTORC1 regulation signals through the GATOR1 complex. Loss of function of GATOR1 contributes to several neurodevelopmental disorders and medically refractive epilepsy. Mutations to one of the essential subunits of GATOR1, NPRL2, are sufficient to cause focal epilepsy and schizophrenia; yet, little is known about its role in the nervous system. Here we demonstrate the loss of Nprl2 in excitatory cells in the neocortex and hippocampus is sufficient to cause mTOR-related pathology, decreased survival and spontaneous seizures. By inhibiting mTOR activity with rapamycin we were able to rescue brain size, seizures and survival. We also show that loss of Nprl2 results in a down-regulation of synaptic proteins, and several metabolic disruptions. Furthermore, we demonstrated that the significantly increased glycine was a primary mechanism which increased synaptic excitability. This suggests that targeting the glycine binding site on the NMDA receptor may be a targeted therapy for future study.
We also demonstrated, in three different cell-specific conditional knockout models, distinct behavioral profiles which points to the importance of Nprl2 in various neurodevelopmental disorders. These findings demonstrate the multifaceted effects of Nprl2 loss in excitatory cells- which demonstrate seizures and early mortality; excitatory and inhibitory neurons- which had seizures, hyperactivity, social and learning deficits; inhibitory cells- which demonstrated severe hyperactivity, social and learning deficits; and Purkinje cell-specific loss- which had seizure susceptibility, reversal learning deficits and delayed-onset social deficits and altered PPI. These findings highlight the significant role NPRL2 has in the nervous system and future studies in these models will aid in understanding and potentially developing targeted therapies to address the molecular and cellular mechanisms underlying NDDs and seizures in NPRL2 loss