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The South Asian cardiometabolic curse: awareness and action
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
Development of a Holistic Specialty Interest Assessment Tool: A Pilot Project for a Resource Allocation Paradigm
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: Current specialty matching tools quantify students' enjoyment completing highly specific tasks. However, the importance of accounting for multifaceted influences on specialty choice grows.
OBJECTIVE: Our purpose was to better understand how personality and personal values affect ultimate specialty choice.
METHODS: We performed a literature search to identify important drivers of specialty choice. Next, we created and administered an original specialty interest assessment tool in response to literature search. We used the Ten-Item Personality Inventory (TIPI) to measure personality and we performed multivariate logistic regressions to assess for the significance of personality and personal values in determining specialty choice among current physicians and graduating medical students.
RESULTS: Two-hundred and eight non-graduating medical students, 66 graduating medical students and 819 physicians completed administered surveys. Agreeableness and conscientious were significant in choosing Primary Care (PC) and Life Style Friendly (LF) specialties. Importance of salary was a significant predictor of choice of both PC and LF specialties.
CONCLUSIONS: Personality and personal values were found to be significant predictors of ultimate specialty choice
Cell-Type Specific Requirement for Pyruvate Dehydrogenase in Hematopoiesis and Leukemia Development
Get PDFPages i-xii are misnumbered as pages ii-xiii, and page 142 is misnumbered as page 121.When I joined the lab, it was already established that pyruvate dehydrogenase complex (PDC) was required for double positive (DP) T cells, and for the initiation of T- cell acute lymphoblastic leukemia (T-ALL). However, it was not known if lymphoid-specific deletion of PDHA1 using lymphoid-specific Cre line (CD2Cre, CD4Cre) would provide us with a similar phenotype as pan-hematopoietic deletion of PDHA1 using Mx1Cre, and we did not know the metabolic consequences of PDHA1 deletion in the thymus versus bone marrow. Our metabolomics analysis led us to investigate the contribution of glucose in the thymus versus bone marrow, leading us to develop low cell number isotope-tracing method in hematopoietic stem and progenitor cells (HSPCs) after U-13C glucose tracing. The conclusion that PDC is required in DP and T-ALL cells was previously established via flow and transplantation analysis.
However, it was not known 1) the metabolic consequences of PDHA1 deletion after hematopoietic deletion, and 2) whether the thymus or bone marrow primarily uses glucose as an energy source using in vivo tracing method. U-13C glucose tracing followed by metabolomics analysis in the bone marrow also provided evidence that HSCs do not preferentially utilize glucose, at least evidenced from the metabolites we were able to examine, but this question needs to be further investigated with more extensive low-cell number metabolomics experiments that can detect more metabolites. My work in collaboration with S. Mahesula also arrived at a conceptually novel discovery that the role of PDC in the thymus is to prevent upstream metabolites from accumulating, rather than to generate acetyl-CoA to fuel the TCA cycle. Moreover, I showed that PDC is needed to maintain NAD+/NADH homeostasis in the thymus.
Here, I present that PDC was not required to generate acetyl-CoA or maintain levels of TCA cycle metabolites but was required to prevent pyruvate accumulation and to maintain glutathione levels and redox homeostasis. Moreover, I present results highlighting the efforts to rescue metabolic defects seen in the PDHA1-deficient mice. My work shows the importance of employing in vivo approaches to characterize the metabolic requirement of DP thymocytes and T-ALL cells, and through this work we could draw a conclusive result that some metabolic characteristics of cancer cells may be inherited from the metabolism of the normal cell type of origin
The Role of Hypertension and Type II Diabetes in Glaucoma Severity
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: Hypertension (HTN) and Type II Diabetes (DM) are risk factors associated with the development of primary open angle glaucoma (POAG), but the effects of these diseases on POAG severity are not well known.
OBJECTIVE: To evaluate for differences in glaucoma severity for patients with (1) HTN alone, (2) DM alone, (3) both HTN and DM, and (4) neither HTN nor DM.
METHODS: In this IRB approved retrospective chart review study, we selected a total of 767 patients with POAG or ocular hypertension (OHT) seen at UT Southwestern Aston eye clinic in Dallas, Texas. The inclusion criteria were patients who were > 18 years old, had open angles, and no evidence of secondary glaucoma or retinal/optic nerve pathologies. Variables collected included: visual acuity, intraocular pressure, central corneal thickness, visual fields, blood pressure, HgbA1c, demographic factors (age, race, gender), and optic coherence tomography angiography (OCTA) data such as mean macular vessel density (VD), peripapillary VD, peripapillary retinal nerve fiber layer (RNFL), and total ganglion cell complex (GCC).
RESULTS/CONCLUSION: Out of a total of 1104 participants reviewed, we selected 767. Among the included patients, there were 149 (19.5%) subjects without POAG, 122 (15.9%) with OHT, 95 (12.4%) with mild POAG, 137 (17.9%) with moderate POAG, and 262 (34.2%) with severe POAG. Regarding the four comorbid disease groups of interest, there were 212 (27.6%) control patients with neither HTN nor DM, 318 (41.5%) with HTN alone, 47 (6.1%) with DM alone, and 190 (24.8%) with both HTN and DM. All comorbidity groups had more female than male, and the average age of the groups ranged from 66-72 years old. We did not find a significant difference in the distribution of glaucoma severity between those with HTN/DM and those without. OCTA analysis corroborated our findings
Addressing urgent privacy challenges in healthcare through the lens of contextual integrity
Get PDF[Note: The slide presentation is not available from this event.] Tuesday, February 14, 2023; noon to 1 p.m. (Central Time); via Zoom. "Addressing Urgent Privacy Challenges in Healthcare Through the Lens of Contextual Integrity". Helen Nissenbaum, Ph.D., Professor of Information Science and Director of Digital Life Initiative, Cornell Tech, New York City, New York.[Note: The slide presentation is not available from this event.] In healthcare, as in other social spheres, digital technology has posed dire challenges to entrenched approaches to privacy. Yet, as a fundamental cornerstone of ethical healthcare, privacy cannot be allowed to erode. The theory of contextual integrity (CI), which defines privacy as appropriate flow of personal information answers the need for a meaningful concept of privacy that, simultaneously explains its value to individuals and to societies. CI requires that we bend away from one-dimensional ideas, which for decades have gripped the privacy domain, namely, control over information about ourselves, stoppage of flow, or fetishization of specific, "sensitive" attributes (e.g., identity, health). This lecture will review key ideas behind CI, contrast it with alternative accounts, and apply these ideas to the domain of intensive health care and health research domains, distinctive not only for their societal importance but for their ages-long attentiveness to privacy.UT Southwestern--Program in Ethic
Copper-catalyzed selective allylic alkylation of allylic systems using Grignard reagents
Get PDFThe construction of carbon-carbon bonds has always been at the forefront of synthetic organic chemistry for generating products of greater utilities. Owing to their extraordinary applications in the synthesis of a wide range of therapeutic small molecules and natural products, the design and the development of new and practical synthetic methodologies will always be desirable. Our studies on the development of new catalytic methods to synthesize polycyclic aromatic compounds via a benzannulated reaction and the formation of valuable allylic products from selective allylic alkylation reactions are described.
First, the development of N-Heterocyclic carbene catalyzed benzannulation will be discussed based on a venerable reaction called the Hauser-Kraus annulation, developed in 1978 by F. M. Hauser and G. A. Kraus. This reaction has enormous utilization in the synthesis of complex natural products with dihydroxynaphthalene and anthraquinone core structures. However, this method suffers from several drawbacks in a complex molecular setting. We design and develop the first catalytic platform of this traditional reaction based on NHC-mediated umpolung chemistry. The method provides a milder protocol for the synthesis of polycyclic aromatic compounds and also eliminates the drawbacks of the traditional Hauser-Kraus annulation.
Secondly, the development of a series of general but highly selective methods for the synthesis of functionalized olefin products from simple unsaturated systems will be described. Unsaturated hydrocarbons are usually low-cost and highly abundant chemical species, making them attractive target substrates for their transformation into synthetically valuable products. However, they pose various challenges during their conversion into a selective product as they possess electronically and sterically similar carbon-hydrogen bonds and often require a highly selective reaction to differentiate between them. The catalytic methods described herein exploit the power of transition-metal catalysis to control the selective formation of allylic alkylation products through a new carbon-carbon bond formation using Grignard reagents. More specifically, two new copper-catalyzed methods will be discussed: (i) a regioselective method for the alkylation of unbiased internal allylic carbonates (ii) a branch selective method for the alkylation of terminal alkenes
The Winter of My Soul
Get PDFThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.Describes the emptiness of love lost and the desire to find it again
A Novel Role for HAPLN1 in Skeletal Development
Get PDFAdolescent idiopathic scoliosis (AIS) is a potentially progressive spinal curvature that occurs during rapid growth and has a multi-factorial genetic etiology. Prior genetic studies in humans and animal models support differences in cartilage development in the pathogenesis of AIS. Here, we performed genome sequencing in families with inherited AIS and identified a co-segregating rare variant in the HAPLN1 gene. HAPLN1 encodes Hyaluronan and Proteoglycan Link Protein 1, also known as Cartilage Link Protein, that is reported to stabilize the extracellular matrix (ECM) by binding hyaluronic acid (HA) and proteoglycans in multiple tissues. One variant, p.C304S, was predicted to disrupt a critical disulfide bridge of the HAPLN1 C-terminal loop domain. In transient over-expression experiments, we detected wild type mouse Hapln1 protein in the cell lysate, media, and ECM, while Hapln1 p.C306S (C304S in human) was detected in cell lysate and media, but not in the ECM. A truncated Hapln1 p.C306fs*5 (ET) lacking the C-terminal loop domain was detected only in the cell lysate. By mutagenesis experiments we found that replacing cysteines in Hapln1 primary disulfide bridges disrupted secretion and retention in the ECM, whereas replacing cysteines in secondary loops disrupted ECM retention only. Thus, all disulfide loops are required for ECM retention. Mice were engineered to harbor the orthologous mutations. While Hapln1ET/ET mice died shortly after birth, exhibiting a chondrodysplastic phenotype with shortened limbs and dome-shaped head, Hapln1C306S/C306S mice were viable, born at expected Mendelian ratios, and showed no significant skeletal malformations up to one year of age. Surprisingly, we were unable to detect Hapln1 protein in tissues of Hapln1C306S/C306S mice although they were phenotypically normal. Furthermore, we found that Hapln1 negatively regulates apoptosis in growth plate hypertrophic zones. Collectively, our data suggest an essential function for Hapln1 that is potentially independent of its role in the ECM
Validation of a Scale Measuring Perceived Burdensomeness and Thwarted Belongingness in Adolescents
No full textDeath by suicide is of growing concern for youth ages 14 to 24. In 2019, it was the second leading cause of death for this age group (CDC, 2019). To better understand why suicide rates have been on the rise over the last decade, various theoretical models were created. One of those theories, The Interpersonal Psychological Theory of Suicide (IPTS), was created by Thomas Joiner and has received significant empirical support across the world (Chu et al., 2017; Joiner, 2005). This theory includes two constructs, perceived burdensomeness and thwarted belongingness, to facilitate the understanding of the origin of suicidal ideation. Perceived burdensomeness is a construct reflecting the perception one's mere existence is a burden on others, and one's life is worthless. Thwarted belongingness describes the perception that one lacks reciprocally loving or caring relationships. These two constructs are hypothesized to be the final pathways by which suicidal ideation occurs. The most widely used assessment tool to measure perceived burdensomeness and thwarted belongingness is the Interpersonal Needs Questionnaire (INQ), which was initially designed for adults. This study addresses the measurement of these constructs by creating and validating a new scale specifically for the adolescent population using concrete scenarios and developmentally appropriate language. The scenario-based items were designed to reflect various contexts during which adolescents likely experience perceived burdensomeness and thwarted belongingness via qualitative interviews and review of the literature. A factor analysis of the new scale resulted in two subscales reflecting perceived burdensomeness, including worthlessness, and thwarted belongingness. The scale also demonstrated strong reliability and validity when compared to the INQ. It also was moderately correlated with concurrent measures of depression and suicidal ideation, and weakly correlated with fearlessness about death reflecting adequate convergent and discriminant validity. In both the new scale, and the INQ, perceived burdensomeness and thwarted belongingness were highly correlated. This suggests these cognitive-affective states might arise together, particularly in real-life situations and in clinical samples. In examination of the IPTS model, the interaction of perceived burdensomeness and thwarted belongingness, when measured both by the new scale and the INQ, did not contribute any significant variance to concurrent suicidal ideation when controlling for depressive symptoms. In this sample, depression was the only significant contributor in the model. This contradicts the IPTS and suggests an important area of consideration in future investigations of the model. The scale addressed gaps in the literature regarding measurement of perceived burdensomeness and thwarted belongingness across varying relational contexts (i.e., family versus friends) in a developmentally appropriate way. Exploratory analyses using the scale also provided evidence supporting a difference in the extent to which perceived burdensomeness and thwarted belongingness are elicited across domains and roles for clinically depressed adolescents. This has the opportunity to provide clinically relevant information when trying to target these cognitive-affective states in treatment. Future research can use this scale to continue testing the relationship between the IPTS variables across contexts and suicidal ideation in both clinical and community samples
Sex differences in severity of metabolic complications in patients with congenital generalized lipodystrophy
No full textThe attached file includes supplementary tables. This submission meets the Extended Data Sets and Supplemental Materials requirements that are included in author guidelines for the Journal of Clinical Endocrinology & Metabolism (Print ISSN 0021-972X, Online ISSN 1945-7197).CONTEXT: Previous data support a higher prevalence of metabolic complications in females affected with familial partial lipodystrophy than in males. However, whether there are any sex differences in the prevalence and severity of metabolic complications among patients with congenital generalized lipodystrophy (CGL) remains unclear.
OBJECTIVES: To compare prevalence of metabolic complications and metabolic parameters between males and females with CGL.
DESIGN: A retrospective, cross-sectional comparison.
SETTINGS: Patients from two tertiary referral centers from Northeastern Brazil - Universidade Federal do Rio Grande do Norte, Natal, and Universidade Federal do Ceará, Fortaleza.
PATIENTS: A total of 44 females (age 2-51 years) and 28 males (age 5-46 years) with CGL. Twenty-six (7 M, 19 F) had genotypically confirmed CGL type 1, 43 (20 M, 23 F) had CGL type 2, and 3 patients were not genotyped.
MAIN OUTCOME MEASURES: Prevalence of diabetes mellitus and hypertriglyceridemia, and metabolic variables.
RESULTS: Females with CGL, as compared to males, had significantly increased prevalence of diabetes (82% vs. 54%; p<0.01) and hypertriglyceridemia (91% vs. 71%; p=0.05); and had higher median fasting serum triglycerides levels (383 vs. 221 mg/dL; p=0.01), but not statistically significantly higher median hemoglobin A1c (7.9% vs. 6.5%; p=0.37) and fasting serum glucose levels (138 vs. 89 mg/dL; p=0.06).
CONCLUSIONS: Compared to males, females with CGL have increased prevalence of metabolic complications, such as diabetes and hypertriglyceridemia, suggesting need for close monitoring of metabolic parameters, and early and aggressive intervention among them