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The author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2025 On My Own Time™ (OMOT) Art Show.So much of medicine is about human connection -- the laying of hands on the sick; the connection between my humanity as a clinician and the human of the patient in front of me. Sometimes, the same signals that reflect life (a pulse) can portend death (a very fast pulse reflecting a cardiac problem -- in this case, 200 beats a minute being far too fast). It's in these moments -- where I am feeling for the patient's pulse while I can feel my own heart racing because of my concern for her -- where the human connection manifests. Palpably
listening
The author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2025 On My Own Time™ (OMOT) Art Show.written after the death of my mother last yea
T-cell based therapies in multiple myeloma
Detailed 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
Impact of a Web-Based Psychosocial Intervention on Perceived Ability to Address Cancer-Related Concerns in Adolescents and Young Adults with Cancer
STATEMENT OF THE PROBLEM: Adolescents and young adults (AYA) with cancer experience unique psychosocial needs that often go unmet due to a lack of age-specific healthcare practices and interventions. Subsequently, AYAs report high levels of psychosocial needs that contribute to high levels of distress. Despite a clear need for specific types of psychosocial support, there is a dearth of empirically validated, AYA-specific, psychosocial interventions available. Research shows low rates of AYA engagement in psychosocial support services, as well as deficits in the information, motivation, and behavioral skills needed for AYAs to address their cancer-related concerns. Behavioral skills refer to a person’s 1) objective (i.e., actual) ability and 2) perceived ability (PA) to perform specific health behaviors, such as adhere to treatment, manage symptoms, or engage in follow-up care. Interventions targeting these deficits in information, motivation, and behavioral skills must incorporate AYA care preferences to effectively engage AYAs and identify and address unmet needs. The current project proposes PA as one mechanism of action of psychosocial intervention and presents the AYA Care Plan as an intervention to target information, motivation, and behavioral skill deficits in AYAs with cancer.
METHODS: The current project includes a narrative review of AYA experiences and proposes a conceptual application of the Information-Motivation-Behavioral Skills model of health behavior to the AYA Care Plan—a web-based psychosocial intervention for AYAs with cancer. Additionally, the project presents findings from a mixed methods study examining the AYA Care Plan’s impact on PA, as well as facilitators of and barriers to PA. Participants (n = 22) were recruited during routine oncology appointments at two outpatient cancer centers and completed an online distress and needs assessment screening at the time of their appointments. Within two weeks of screening, AYAs participated in qualitative interviews exploring facilitators of and barriers to PA. Participants also completed a pre-intervention measure of PA, received and explored their AYA Care Plan, and completed a post-intervention measure of PA during qualitative interviews.
RESULTS: No statistically significant changes in total PA score from pre- to post-intervention were found; however, qualitative results demonstrated that a majority of participants perceived an increase in their PA from pre- to post-intervention. AYAs identified knowledge, beliefs and attitudes, and support, or a lack thereof, as facilitators of and barriers to PA.
CONCLUSIONS: Findings suggest that AYAs with perceived unmet information needs, insufficient support, and/or beliefs and attitudes inhibiting their PA to address their concerns may benefit most from the AYA Care Plan. For these AYAs, the care plan may contribute to PA by providing information about cancer-related concerns and strategies to address concerns, as well as prompting shifts in beliefs and attitudes and intention to address concerns. Results reiterate the significant roles that knowledge, beliefs and attitudes, and support play in either facilitating or hindering AYAs’ PA to address their concerns. Findings warrant further investigation into the AYA Care Plan’s impact on PA in additional patient populations and clinical settings, as well through other modes of delivery
Pharmacological Intervention Reduces Hippocampal Hyperactivity in a Mouse Model of Psychosis
Psychosis is a predominant symptom domain in the conventional diagnosis of schizophrenia as well as in other psychiatric disorders. Current pharmacological treatment options abound in side effects, leading to poor patient adherence. Therefore, we are in need of novel mechanistic treatment targets. Prior research has identified the molecular and behavioral characteristics of a model in animals putatively parallel to hippocampal hyperactivity in human schizophrenia brain. A reverse-translational mouse model of psychosis has been developed based on subchronic chemogenetic inhibition of dentate gyrus (DG) during adolescence and it could become a candidate for testing antipsychotic drug activity. The subchronic DG inhibition causes a lasting downstream hippocampal hyperactivity, along with behavioral consequences. This doctoral dissertation examines the influence of antipsychotic and experimental compounds on hippocampal subfield activity as well as their influence on correcting aberrant behaviors with face validity to psychosis. The current scientific consensus in respect to psychosis and hippocampus is briefly introduced in Chapters 1 and 2. In Chapter 3, I have delineated pharmacology used in these studies. The drugs used were haloperidol - a classic antipsychotic, and levetiracetam - anticonvulsant with proven pro-cognitive effect, but experimental in the field of psychosis.
In Chapter 4, I have examined the effects of subchronic Compound 21 administration one week after DG inhibition by quantifying principal cell activity in hippocampal subfields. The CA3 and CA1 were hyperactive compared to control mice. The effects of acute drug administration were assessed: all drugs tested showed robust decrease of baseline CA3 and CA1 hyperactivity (haloperidol 0.3mg/kg ip, levetiracetam 5mg/kg ip).
Subsequently, in Chapter 5 I have performed Social Recognition Memory test with and without haloperidol (1.75mg/kg/day oral) or levetiracetam (100mg/kg/day oral), as well as cued and contextual fear conditioning with haloperidol (1.75mg/kg/day oral). Haloperidol, but not levetiracetam, rescued the deficit in Social Recognition Memory. However, haloperidol did not alter the increased freezing in fear conditioning paradigm.
Finally, in Chapter 6, I describe how the results of this dissertation pave the way to further research of the diverse mechanisms of decreasing hippocampal hyperactivity that could lead to amelioration of psychosis-like symptoms and constitute a translational potential
A Novel Squid Glaucoma microShunt for Controlled Release of Aqueous Humor
BACKGROUND: Glaucoma is a progressive, multifactorial optic neurodegenerative disease and is the second leading cause of blindness, affecting 80 million patients globally. Elevated intraocular pressure (IOP) is the main modifiable risk factor. When medications and laser therapies fail, glaucoma drainage devices (GDDs) are implanted. Current GDDs have major drawbacks: 1) large sizes requiring extensive surgical dissection, 2) uncontrolled aqueous humor (AH) release risking vision loss, and 3) prolonged inflammation and fibrosis leading to a complication rate over 50% at 5 years. To address this clinical need, we developed a novel GDD, the Squid Glaucoma microShunt (SGS) which has been designed to release AH in a slow and controlled fashion.
OBJECTIVE: The aims are to 1) review the chemical and physical properties of biocompatible polymers, 2) understand the properties of ultrananocrystalline diamond (UNCD) coating and its fabrication methods, 3) identify the top three optimal polymers for fabrication, 4) survey glaucoma specialists on the design of the SGS to stimulate further ideas for development, and 5) fabricate 3D-printed prototypes.
METHODS: The characteristics of various polymers and UNCD were investigated through literature review and consultations with materials science experts. Top polymer candidates were assessed based on the following criteria: durability over time, flexibility/toughness, thermal capacity, ease of fabrication, biocompatibility, cost, physical form, U.S. Food and Drug Administration (FDA) approval, and prior use for ophthalmic applications. Glaucoma specialists were emailed a brief description of the SGS along with a 4-question survey: likelihood of using the SGS in their practice, advantages/disadvantages, and challenges experienced with current GDDs. 3D-printed prototypes of the SGS and twin microforceps were fabricated in collaboration with microfluidic device manufacturers.
RESULTS: The three polymers that were selected for future laboratory testing include polytetrafluoroethylene (PTFE), polystyrene (PS), and polydimethylsiloxane (PDMS). Five responses from glaucoma specialists were received, and they provided an average 4.4/5 rating for the likelihood of using the SGS in their practice. 3D printed SGS prototypes with precise dimensions were fabricated using projection micro stereolithography along with metal microforceps prototypes. An alternative biofluid-based UNCD coating procedure that can be conducted at room temperature was developed in collaboration with Orlando Auciello, PhD
Targeting BMP, activin, and TGF beta signaling in pulmonary hypertension: lessons from human genetics, disease models and clinical trials
Detailed 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
Structural heart disease interventions in safety net populations
Detailed 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
Equitable communication: building trust and overcoming differences
Detailed 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
Investigation of Divergent Metabolic Programs in the Tumor-Immune Microenvironment
The current immune metabolism field has been using the term lactate and lactic acid interchangeably, with the notion that lactate and lactic acid are waste products of highly glycolytic cancer cells that negatively affects TIL function and viability to promote tumorigenesis. However, it is yet unclear whether lactate or its protonated counterpart lactic acid is responsible for the dampening of immune cell functions within the TIME. The in vitro cell culture studies aimed to delineate the impact of lactate and lactic acid in the context of cancer growth. Data showed that lactate alone significantly impairs cancer cell metabolism independent of the acidic pH environment. Additionally, therapeutic lactate treatment significantly increased the glycolytic activity and effector functions of CD8+ T-cells, contrary to the current understanding that lactate dampens immune cell functions. The comparison study between lactate and lactic acid further demonstrated that CD8+ T-cells undergo cell death that is dependent on pH levels, with approximately 50% of T-cell death occurring at pH level below 6.0, whereas cancer cells were able to metabolically adapt to the acidic environment and sustain growth. These findings provide a new perspective that challenges the current notion that lactate is considered a "pro-tumor" metabolite. In vivo metabolomics study of tumor cells and tumor-infiltrating CD8+ T-cells revealed that lactate initiates a divergent metabolic reprogramming in the two cell types. Systemic lactate treatment suppressed tumor glycolytic activities while boosting CD8+ T-cell glycolytic rate and effector function. Such divergent changes in two cell types provide a basis for developing potent antitumor responses in the complex heterogeneous tumor microenvironment. The impact of lactate on glycolytic flux modulation on both tumor cells and CD8+ T-cells, therefore, exposes a previously undefined difference in metabolic programs between the two cell types that can be exploited in the immune-suppressive tumor microenvironment