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UNTHSC Scholar is an open access repository of the intellectual output and publicly available materials of the university. UNTHSC Scholar provides stable access to data, highlights community partnerships and engagement, and enables discovery of these works by the international scientific community. It preserves the history, growth and innovation of the University of North Texas Health Science Center as an institution.

 

Recent Submissions

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Design and Synthesis of D(3)R Bitopic Ligands with Flexible Secondary Binding Fragments: Radioligand Binding and Computational Chemistry Studies
(MDPI, 2024-01-11) Tian, Gui-Long; Hsieh, Chia-Ju; Taylor, Michelle; Lee, Ji Youn; Luedtke, Robert R.; Mach, Robert H.
A series of bitopic ligands based on Fallypride with a flexible secondary binding fragment (SBF) were prepared with the goal of preparing a D(3)R-selective compound. The effect of the flexible linker ((R,S)-trans-2a-d), SBFs ((R,S)-trans-2h-j), and the chirality of orthosteric binding fragments (OBFs) ((S,R)-trans-d, (S,R)-trans-i, (S,S)-trans-d, (S,S)-trans-i, (R,R)-trans-d, and (R,R)-trans-i) were evaluated in in vitro binding assays. Computational chemistry studies revealed that the interaction of the fragment binding to the SBF increased the distance between the pyrrolidine nitrogen and ASP110(3.32) of the D(3)R, thereby reducing the D(3)R affinity to a suboptimal level.
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Dopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function-Not a New Concept, but Neglected Reality
(MDPI, 2024-01-23) Salvatore, Michael F.
The mechanistic influences of dopamine (DA) signaling and impact on motor function are nearly always interpreted from changes in nigrostriatal neuron terminals in striatum. This is a standard practice in studies of human Parkinson's disease (PD) and aging and related animal models of PD and aging-related parkinsonism. However, despite dozens of studies indicating an ambiguous relationship between changes in striatal DA signaling and motor phenotype, this perseverating focus on striatum continues. Although DA release in substantia nigra (SN) was first reported almost 50 years ago, assessment of nigral DA signaling changes in relation to motor function is rarely considered. Whereas DA signaling has been well-characterized in striatum at all five steps of neurotransmission (biosynthesis and turnover, storage, release, reuptake, and post-synaptic binding) in the nigrostriatal pathway, the depth of such interrogations in the SN, outside of cell counts, is sparse. However, there is sufficient evidence that these steps in DA neurotransmission in the SN are operational and regulated autonomously from striatum and are present in human PD and aging and related animal models. To complete our understanding of how nigrostriatal DA signaling affects motor function, it is past time to include interrogation of nigral DA signaling. This brief review highlights evidence that changes in nigral DA signaling at each step in DA neurotransmission are autonomous from those in striatum and changes in the SN alone can influence locomotor function. Accordingly, for full characterization of how nigrostriatal DA signaling affects locomotor activity, interrogation of DA signaling in SN is essential.
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The impact of 17beta-estradiol on the estrogen-deficient female brain: from mechanisms to therapy with hot flushes as target symptoms
(Frontiers Media S.A., 2024-01-23) Prokai-Tatrai, Katalin; Prokai, Laszlo
Sex steroids are essential for whole body development and functions. Among these steroids, 17beta-estradiol (E2) has been known as the principal female" hormone. However, E2's actions are not restricted to reproduction, as it plays a myriad of important roles throughout the body including the brain. In fact, this hormone also has profound effects on the female brain throughout the life span. The brain receives this gonadal hormone from the circulation, and local formation of E2 from testosterone via aromatase has been shown. Therefore, the brain appears to be not only a target but also a producer of this steroid. The beneficial broad actions of the hormone in the brain are the end result of well-orchestrated delayed genomic and rapid non-genomic responses. A drastic and steady decline in circulating E2 in a female occurs naturally over an extended period of time starting with the perimenopausal transition, as ovarian functions are gradually declining until the complete cessation of the menstrual cycle. The waning of endogenous E2 in the blood leads to an estrogen-deficient brain. This adversely impacts neural and behavioral functions and may lead to a constellation of maladies such as vasomotor symptoms with varying severity among women and, also, over time within an individual. Vasomotor symptoms triggered apparently by estrogen deficiency are related to abnormal changes in the hypothalamus particularly involving its preoptic and anterior areas. However, conventional hormone therapies to "re-estrogenize" the brain carry risks due to multiple confounding factors including unwanted hormonal exposure of the periphery. In this review, we focus on hot flushes as the archetypic manifestation of estrogen deprivation in the brain. Beyond our current mechanistic understanding of the symptoms, we highlight the arduous process and various obstacles of developing effective and safe therapies for hot flushes using E2. We discuss our preclinical efforts to constrain E2's beneficial actions to the brain by the DHED prodrug our laboratory developed to treat maladies associated with the hypoestrogenic brain."
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Profession-based manual therapy nomenclature: exploring history, limitations, and opportunities
(Informa UK Limited, trading as Taylor & Francis Group, 2023-12-17) Degenhardt, Brian; van Dun, Patrick L.S.; Jacobson, Eric; Fritz, Sandy; Mettler, Paul; Kettner, Norman; Franklin, G.; Hensel, Kendi; Lesondak, David; Consorti, Giacomo; Frank, Leah; Reed, William R.; MacDonald, Cameron; Kremen, Vaclav; Martin, Crystal; Landels, Bernie; Standley, Paul
OBJECTIVE: The International Consortium on Manual Therapies (ICMT) is a grassroots interprofessional association open to any formally trained practitioner of manual therapy (MT) and basic scientists promoting research related to the practice of MT. Currently, MT research is impeded by professions' lack of communication with other MT professions, biases, and vernacular. Current ICMT goals are to minimize these barriers, compare MT techniques, and establish an interprofessional MT glossary. METHODS: Practitioners from all professions with training in manual therapies were encouraged by e-mail and website to participate (www.ICMTConferene.org). Video conferences were conducted at least bimonthly for 2.5 years by profession-specific and interprofessional focus groups (FGs). Members summarized scopes of practice, technique descriptions, associated mechanisms of action (MOA), and glossary terms. Each profession presented their work to the interprofessional FG to promote dialogue, understanding and consensus. Outcomes were reported and refined at numerous public events. RESULTS: Focus groups with representatives from 5 MT professions, chiropractic, massage therapy, osteopathic, physical therapy and structural integration identified 17 targeting osseous structures and 49 targeting nonosseous structures. Thirty-two techniques appeared distinct to a specific profession, and 13 were used by more than 1. Comparing descriptions identified additional commonalities. All professions agreed on 4 MOA categories for MT. A glossary of 280 terms and definitions was consolidated, representing key concepts in MT. Twenty-one terms were used by all MT professions and basic scientists. Five terms were used by MT professions exclusive of basic scientists. CONCLUSION: Outcomes suggested a third to a half of techniques used in MT are similar across professions. Additional research is needed to better define the extent of similarity and how to consistently identify those approaches. Ongoing expansion and refinement of the glossary is necessary to promote descriptive clarity and facilitate communication between practitioners and basic scientists.
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Single-Center Analysis of the Off-Hour Effect in Cardiogenic Shock Outcomes
(2022-12) Harrison, Caroline R.; Berg, Rance E.; Ortega, Sterling
The off-hours effect is a phenomenon where patients admitted during nights and weekends have poorer outcomes than those admitted during weekdays. This observation is often more pronounced in emergent conditions such as cardiogenic shock. Few studies have investigated the presence of an off-hour effect in patients with cardiogenic shock. In my thesis project, I explored the existence of an off-hour effect in 155 cardiogenic shock cases at a major urban hospital by evaluating patient outcomes. Patients admitted during off-hours had higher complication rates (OR=2.66, 95% CI, 1.29 to 5.49; p=0.01). I also found that patients admitted during on-hours waited longer to receive mechanical circulatory support devices after being admitted; however, this did not appear to negatively effect on-hour patient outcomes. While it appears that admission time does influence patient outcomes, the underlying cause for this effect is not yet understood.