University of North Texas
UNTHSC Scholar (University. of North Texas Health Science Center)Not a member yet
6724 research outputs found
Sort by
Evaluating the STEADI initiative in African Americans, Mexican Americans, and Non-Hispanic Caucasians with different cognition levels for fall prevention
No full textPoster Highlight: Texas College of Osteopathic Medicine - Research, RAD 2025 Award Winning Posters & Oral PresentationsObjective: The CDC has created the STEADI initiative, a collection of functional tests to evaluate fall risks within the elderly population. However, there is limited data in accessing its efficacy across different racial groups. With minorities disproportionally suffering from dementia, this research aims to apply the STEADI initiative across underrepresented minority groups. Background: Dementia is a growing health crisis that affects the elderly, with projections of nearly 80 million people affected worldwide by 2030. Individuals with dementia are at a higher risk for falls, a fatal health concern for the elderly. Methods: The Institute of Translational Research was built with a primary goal of reducing racial disparities in healthcare. Using their Health and Aging Brain Structure Health Disparities (HABS-HD) database, three functional tests were used in this study—timed-up-and-go (TUG) test, repeated chair stand test, and the 4-stage balance test (4SBT). Using a two-sample t-test, this research analyzed the functional test performance of African Americans, Mexican Americans, and Non-Hispanic Caucasians with preserved cognition (PC), mild cognitive impairment (MCI), and dementia. Results: Non-Hispanic Caucasians with PC performed better on all functional tests than Mexican Americans with PC with a p value of ≤ 0.001—TUG score of 8.96 and 9.69 and a Repeated Chair Stand test of 9.67 and 10.92 respectively. Non-Hispanic Caucasians with PC had a higher 4SBT score of 11.25 compared to Mexican Americans with PC 10.82. Mexican Americans with dementia performed better on all functional tests than Non-Hispanic Caucasians with dementia. Conclusion: Non-Hispanic Caucasians and African Americans with dementia being screened via STEADI can most benefit from evidence-based fall prevention (EBFP) programs. Mexican Americans with preserved cognition can especially benefit from the STEADI initiative as a screening tool for developing cognitive disorders in the future
Incorporation of community resources across clinics impact in pediatric populations facing Adverse Childhood Experiences (ACEs).
No full textPurpose: To identify the social determinants of health (SDH) and Adverse Childhood Experience (ACE) factors in data collected from the Pediatric Mobile Clinic (PMC) patient population at UNT Health Science Center (UNTHSC) and assess the impact of the intervention on health outcomes. The PMC is a mobile healthcare unit that provides free primary care, vaccines, and physicals to children ages (0-18) in socioeconomically disadvantaged communities, regardless of insurance status. Research indicates that addressing ACEs in vulnerable populations can significantly reduce negative health outcomes. Therefore, in a pragmatic clinical trial, we will evaluate the effectiveness of Trust Based Relational Interventions (TBRI) in mitigating the effects of ACEs on mental health, symptomatology, and chronic disease management using qualitative and quantitative methods. Methods: The data will be obtained by retroactive chart review of the Whole Child Assessment (WCA) and Safe Environment for Every Kid (SEEK) surveys to determine the SDH and ACEs data in PMC patients. Data will include narrative (qualitative) and standardized scale scores (quantitative) measuring physical health, stress, and ACE-related symptoms. Based on the identified needs, we will implement target community interventions to assess the impact on child and family health outcomes. Additionally, we will analyze this data to determine the effects of the COVID-19 pandemic on the prevalence and identify trends in SDHs pre, during, and post-COVID lockdown. Conclusions: The data suggests a prevalence of food insecurity, poison control information, and food not lasting long as the top three ACEs experienced in the PMC population. Further analysis will evaluate the effectiveness of TBRI interventions in improving health outcomes
Phenethylaminylation: Preliminary In Vitro Evidence for the Covalent Transamidation of Psychedelic Phenethylamines to Glial Proteins using 3,5-Dimethoxy-4-(2-Propynyloxy)-Phenethylamine as a Model Compound
No full textPurpose: Psychedelics are well known for their ability to produce profoundly altered states of consciousness. But, more importantly, the effects of psychedelics can influence neurobehavioral changes that last well after these acute subjective effects end. This phenomenon is currently being leveraged in the development of psychedelic-assisted psychotherapies for the treatment of multiple neuropsychiatric disorders. The cellular and molecular mechanisms by which single doses of psychedelics are able to mediate long-term cognitive changes are an active area of research. We propose a hypothesis that psychedelics may contribute to long term changes in cellular state by covalently modifying proteins through the transglutaminase 2-mediated transamidation of their amine termini to glutamine carboxamide residues on target proteins. Methods: We synthesized 3,5-dimethoxy-4-(2-propynyloxy)-phenethylamine, a propargylated analogue of mescaline – the classic serotonergic psychedelic phenethylamine found in cacti species. In a primary human astrocyte cell culture model, we tracked proteins modified by our model phenethylamine by biotinylating the compound’s terminal alkyne moiety through a copper(I)-catalyzed azide-alkyne cycloaddition reaction (“click-chemistry”). Results: We generated preliminary proteomic data indicating that a diverse array of glial proteins may be substrates for transglutaminase 2-mediated covalent monoaminylation by psychedelic phenethylamines (“phenethylaminylation”) including metabolic enzymes, cytoskeletal elements, signaling molecules and more. Conclusions: A diverse array of proteins may be potential targets of covalent modification by certain psychedelic compounds, which may represent a novel mechanism by which these drugs exert long-term effects on a molecular level
Differential Expression Profiles of miRNA and piRNA in Alzheimer's Disease as a Diagnostic Tool
No full textIntroduction: Alzheimer’s Disease (AD) is the leading form of dementia and continues to be a top cause of death despite recent advancements in the field. Treatment for the disease remains largely tied to abating symptoms rather than pathology. Even the handful of recently approved treatments claiming to slow the pathology show limited success. Whether this is because the pathological targets are wrong, or the timing of treatment comes too late is up for debate. In either case, small extracellular vesicles (sEVs) may represent a useful tool. These sEVs are capable of regulating cellular function through their RNA cargo, and their expression profiles may hold the key to revealing new therapeutic targets, or to detect the disease before symptoms develop and the pathology has spread too far to reverse. Methodology: We extracted sEVs from AD and non-AD human brains (n=6), extracted RNA for sequencing, and analyzed the micro RNA (miRNA) and piwi-interacting RNA (piRNA) profiles between the groups, using Qiagen’s RNA-Seq analysis portal for miRNA and DESeq2 from the Bioconductor R package for piRNA. Gene targets for miRNA’s of interest were pulled from the miRDB and existing literature, while piRNA targets were predicted using blast and KEGG analysis. Results: We found significant differences in the cargo profiles of both miRNA and piRNA between AD and non-AD brains, with 38 miRNAs and 11 piRNAs being differentially expressed. Top miRNA targets included miR-206, miR-486-5p, miR-4516, and miR-219. Top piRNA targets included piR-6565525, piR-2947194, piR-7181973, and piR-7326987. These targets all have implications in the literature or predicted targets that are relevant to current theories of AD pathology. The miRNA targets were further validated by qPCR to confirm the direction and scale of differential expression seen in the RNA sequencing data. Conclusions: The relevance of the top miRNA and piRNA targets to AD related pathways suggests that these sEV cargo profiles could be useful in determining a diagnosis. Further study will be needed to determine at what point these profiles begin to diverge before they can be considered useful in early detection. Should this divergence occur before symptoms, then the targets may provide insight into which systems are the first to become disrupted and help focus research efforts onto the most critical component
Small molecule inhibitor analogs have differing effects on TNBC than GW525701 parent compound in vitro
No full textOral Presentations: College of Biomedical and Translational Science, RAD 2025 Award Winning Posters & Oral PresentationsPurpose: Triple-negative breast cancer (TNBC) is known for its characteristic lack of three targetable cell receptors: estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors. Therefore, TNBC is much more challenging to treat, often resulting in poorer patient outcomes. Many cancers, including TNBC, have been associated with kinase dysregulation. However, no kinase inhibitor compounds are currently FDA-approved for use against TNBC specifically, indicating the need to develop these compounds and identify the development and future kinase targets. Our lab previously screened a kinase inhibitor compound library to identify kinases of interest in TNBC. GW525701, a small molecule kinase inhibitor compound, has shown promising results by altering TNBC cell morphology, gene expression, and functional migration in vitro. This research has the potential to significantly impact the future of TNBC treatment. GW525701 is highly specific for nine kinases: PDXK, STK10, SLK, STK26, MAP4K4, TNIK, MINK1, DDR1, and EPHB6. Methods: To better understand how this compound inhibits cellular functions, we developed analogs of GW525701 by altering its chemical structure. We then treated a patient-derived xenograft (PDX)-derived TNBC cell line, TU-BcX-4IC, at a log dose range of concentrations for 72 hours. After treating for 72 hours, we stained the cells with 3% crystal violet in methanol and monitored morphologic and cell density changes compared to vehicle-treated controls and GW525701-treated cells. Results: Some analogs could not alter the TNBC phenotype compared to GW525701. In contrast, others, like the PAR-477 and PAR-504, had similar effects on TNBC cells in vitro compared to the parent compound. Conclusions: This phenomenon gives insight into the chemical structures that would be beneficial to include (and exclude) in future therapeutic compounds and, as well as confirms which kinases targeted by GW525701 and related analogs will be relevant for future applications
Comparing Low Grade Glioma Chemotherapy Regimens: Effect of Higher Dose and Lower Frequency Carboplatin Administration on Survival Outcomes and Morbidities in Patients with Pediatric Low-Grade Gliomas
No full textLow-grade gliomas (LGGs) are common central nervous system pediatric tumors that have a high chance of reoccurrence. Neurofibromatosis type 1 (NF1) is known to increase risk of developing a LGG. When complete surgical removal is not feasible, the Children’s Oncology Group (COG) has been recommending a regimen comprised of vincristine and weekly carboplatin at a dose of 175 mg/m2, giving a total carboplatin dose of 7000 mg/m2 as first line treatment. Cook Children’s Medical Center (CCMC) utilizes a different protocol, derived from a Texas Children’s Hospital (TCH) specific protocol that spaces out carboplatin dosing to once every six weeks at a dose of 560 mg/m2 giving a total carboplatin dose of 10080 mg/m2. We aimed to determine the effect that a higher dose and lower frequency carboplatin regimen has on treatment outcomes in patients with LGGs. A secondary aim was to further distinguish if treatment outcomes between the two regimens would vary in patients with neurofibromatosis type 1. CCMC patients from 2019 to June 2024 between the ages of 0 to 18 years at the time of their LGG diagnosis were identified. Patients who received carboplatin/vincristine as their first line of treatment were abstracted utilizing a patient database and the electronic medical record (EMR). Of the 50 patients identified, 26 received the COG regimen (15 had NF1 and 12 did not) and 24 patients who received the institutional protocol (10 with NF1 and 14 without). Chi-square and Mann-Whitney U tests were performed. The event free survival (EFS) of the non-NF1 qweek regimen was 82% (n=9) and that of the q6 week regimen was 36% (n=5). For the NF1 cohort, the EFS of the qweek regimen was 27% (n=4) and for the q6wk regimen was 20% (n=2). There was a significant difference in EFS in non-NF1 patients – the COG regimen group was 8.1 times more likely to relapse than the institutional regimen group. There were no other significant associations seen. This would imply that the CCMC regimen is noninferior and perhaps a better option, especially in non-NF1 patients since fewer chemotherapy visits can reduce logistical, emotional, and financial burdens on patients and their families. However to further support this claim, a larger data pool is needed. This study was limited by a lower than expected number of data available for analysis, which likely explains why only one association was found to be statistically significant. Unfortunately, we are not aware of any other institutions that utilize a q6 week carboplatin regimen (some do use a q4 week regimen) besides TCH. We have reached out to TCH but they are unable to share their data with us at this time. Due to the small data size, it is unclear if these findings are generalizable and so, at this time, we cannot support a change to the COG recommended regimen
Avascular Necrosis and Pseudotumor Cerebri in a Child with Prader-Willi Syndrome on Growth Hormone Therapy
No full textBackground: Recombinant human growth hormone (GH) therapy is a standard of care treatment for children with PWS, as it improves linear growth, tone, and lean muscle mass and may improve central sleep apnea[1, 2]. GH therapy is relatively safe with few known serious complications, which include but are not limited to avascular necrosis (AVN) and pseudotumor cerebri (PTC)[1, 3-5]. To our knowledge, there are no reports of AVN and PTC in a child with PWS on GH therapy. Methods: Herein, we report a case of both AVN and PTC in a child with PWS on GH to raise awareness of possible complications of GH in children with PWS. This study was deemed exempt from human subjects research by the local IRB. The child’s parent provided signed consent for this case study. Case Description: A boy with PWS was started on GH 0.4 mg subcutaneously (SQ) daily (0.85 mg/m²/day) at age 17m (months). At 4y6m (4 years 6 months), his IGF-1 level was elevated at 229 ng/ml (range 27-134 ng/ml), so his dose was decreased to 0.1 mg SQ daily (0.1mg/m²/day). At 4y11m, the child’s mother reported that he had been experiencing frequent trips and falls throughout the prior year. Hip x-ray showed non-acute AVN of left proximal femoral head. Given non-acute status of the AVN and known positive effects on reducing fat mass, GH therapy was cautiously continued at 0.1 mg SQ daily (0.09 mg/m²/day). GH dose was increased to 0.2 mg SQ daily (0.19 mg/m²/day) once imaging confirmed healing phase of AVN at age 5y1m. AVN resolved at age 6y3m. Incidentally, asymptomatic papilledema was found during routine fundoscopic exam by ophthalmologist at age 6y1m; GH was immediately discontinued, and Acetazolamide was initiated. Papilledema resolved in 2 months, and the patient temporarily restarted low-dose GH; however, family ultimately opted to stop GH completely at age 6y10m due to his AVN and PTC history. A year after GH discontinuation at age 7y11m, IGF-1 remained normal at 206 ng/mL (Z=1); height was stable from a year prior at the 78%ile, and BMI was high at 32.79 kg/m² (Z=3.85), but lower than BMI a year prior at GH discontinuation (33.56 kg/m², Z=4.56). Conclusion: AVN and PTC are rare but recognized adverse effects of GH therapy; however, we report for the first time, to our knowledge, AVN and PTC in a child with PWS on GH therapy. Obesity is an independent risk factor for AVN and PTC. As children with PWS commonly suffer from morbid obesity, sleep apnea, poor wound healing, and high pain tolerance[6], they are not only at baseline underlying risk for these complications, but are also at risk for delayed recognition of AVN and PTC. While GH remains standard of care treatment in PWS, risk for AVN and PTC should be considered and clinically monitored
A Hidden Cause of Confusion: Altered Mental Status from B12 Deficiency
No full textBackground: Vitamin B12 is an important vitamin required for normal synthesis of blood cells. Those deficient in B12 can vary in clinical presentation but could present with fatigue, paresthesias, weakness, and gait abnormalities. Case Information: A 63-year-old female presented to the ED with altered mental status without significant past medical history. Patient’s urinalysis was suggestive of an UTI, and she was discharged on keflex. Initially, her AMS was presumed to be secondary to her UTI. The patient returned to the ED 2 days later presenting with continued AMS. Due to her encephalopathy and agitation, it was difficult to obtain further history. Patient complained of hearing a buzzing sound that was not present. Collateral from the husband provided further context into her changes of mental status and denied history of previous psychiatric conditions.. Patient made comments about doing drugs, had paranoia that the church was “out to get [her]”, shaved her head, and threw away her cephalexin. Repeat CBC showed macrocytic anemia (MCV 104.9 FL, Hb 10.7 g/dL) with an unremarkable CMP and chest X-ray. In the ED, the patient received lorazepam, ceftriaxone, and benadryl. On day 2, the patient’s B12 level returned as undetectable (B12 <159 pg/mL) and was without improvement in mental status. Patient has not yet urinated at this point, but subsequent straight catheterization urine drug screen and urinalysis were unremarkable. Patient was started on a 7 day course of 1000mcg IM B12 injections and telepsych consult recommended risperidone 0.5 mg BID. On day 3, the patient was A&Ox4 and coherent in her thoughts and judgement. The patient displayed significant improvement, but still endorsed signs of hallucinations. MRI of the brain with and without contrast showed cerebral atrophy but were unable to find acute findings. On day 4, the patient’s mental status remained stable, but the patient left that evening AMA before discharge orders were put in. Conclusions: The case depicts a unique presentation of altered mental status secondary to B12 deficiency of a rather unknown etiology. The patient’s encephalopathy was confounded with a potential UTI, however the single day of cephalexin and one dose of ceftriaxone would be an inadequate treatment course. Furthermore, improvement from a single dose of risperidone would be unlikely, but cannot be ruled out. On an important note, the patient improved rather rapidly following administration of B12 injections
Grx1/Grx2 Deficiency Links Oxidative Stress and Inflammation to Accelerated Senescence in Mouse Lens Epithelial Cells
No full textPoster Highlight: College of Biomedical and Translational Science, RAD 2025 Award Winning Posters & Oral PresentationsPurpose: This study investigates how Grx1/Grx2 deficiency drives oxidative-stress-induced premature senescence in mouse lens epithelial cells (LECs). By analyzing key senescence markers, cell cycle regulators, and inflammatory mediators at early and late ages, this research aims to elucidate the molecular mechanisms connecting chronic oxidative stress and inflammation to accelerated mLEC senescence and dysfunction. Methods: Primary LECs were isolated from wild-type (WT) and Grx1/Grx2 double knockout (DKO) mice at 1 and 12 months of age. Senescence markers, including β-galactosidase (β-gal), p53, p21, p16, phospho-RB, and senescence-associated secretory phenotype (SASP) factors (IL-6, IL-1, TNF-α), were assessed using β-gal staining and Western blot analysis. Results: LECs from DKO mice displayed significant β-gal staining at both 1 and 12 months, contrasting with WT cells, where senescence markers were largely absent at 1 month but elevated at 12 months. Enhanced β-gal staining in DKO 12-month cells suggested early and accelerated senescence compared to WT. Elevated p53 levels and reduced phospho-RB in 12-month DKO cells (p<0.001; n=3) indicated a heightened senescent response. In WT cells, aging was characterized by decreased p53 levels and dominance of the full-length p53 isoform (p<0.001; n=3), whereas DKO cells showed a shift toward the p53 beta isoform (p<0.001; n=3), implicating the beta isoform in oxidative-stress-induced premature aging. Reduced phospho-RB in both 12-month WT and DKO cells suggested p16-mediated inhibition of RB phosphorylation, leading to permanent cell cycle arrest (p<0.05; n=3). Additionally, IL-6 expression was significantly higher in 12-month DKO cells than WT, pointing to chronic inflammation as a key driver of premature senescence (p<0.05; n=3). Conclusions: This study demonstrates that oxidative stress accelerates lens aging through early and sustained senescence in DKO LECs, characterized by increased β-gal activity, altered p53 isoform expression, and enhanced SASP activity. Elevated IL-6 and reduced phospho-RB levels further implicate chronic inflammation and cell cycle arrest in lens epithelial dysfunction. These findings highlight the critical role of glutaredoxins in mitigating oxidative stress and suggest potential therapeutic strategies targeting inflammation and senescence to delay age-related cataracts
Impairments in Semantic Fluency and Naming: A Cognitive Profile of Alzheimer’s Disease
No full textPurpose: Alzheimer's disease (AD) is characterized by distinct cognitive impairments that differentiate it from other neurodegenerative conditions. This study explores the hypothesis that a combination of poor performance on the Boston Naming Test (BNT) and semantic fluency tasks, alongside relatively preserved phonemic fluency, serves as a reliable cognitive profile for identifying AD. The degradation of semantic memory, a hallmark of AD, is assessed through the BNT and semantic fluency measures, while intact phonemic fluency reflects the relative preservation of executive functioning in the early to moderate stages of the disease. Participants, including individuals with clinically diagnosed AD and age-matched controls, were assessed using these neuropsychological measures. This study explores the hypothesis, indicating that AD patients exhibit significant deficits in the BNT and semantic fluency tasks, whereas phonemic fluency remains comparatively unaffected based on observed clinical patterns. The primary objective is to investigate whether this cognitive profile can reliably differentiate AD and other dementias, specifically vascular dementia from age-matched controls, with implications for early diagnosis and targeted interventions. Specifically, the study will investigate whether a cognitive profile consisting of poor performance on the Boston Naming Test (BNT) and semantic fluency tasks, combined with relatively preserved phonemic fluency, reliably identifies Alzheimer's disease (AD). Methods: Retrospective data from neuropsychological evaluations of 40 patients (25 with AD and 15 age-matched controls) would be collected from an outpatient clinic. Cognitive performance will be assessed using the BNT, semantic fluency, and phonemic fluency tasks. Group comparisons are to be conducted using independent samples t-tests, and effect sizes (Cohen's d) calculated to determine the magnitude of differences between groups. A discriminant function analysis will evaluate the diagnostic utility of the cognitive profile. Results: It is hypothesized that patients with AD will exhibit significantly lower BNT scores compared to controls. It is hypothesized that semantic fluency scores will be significantly reduced in the AD group versus controls. It is hypothesized that no significant differences will be found in phonemic fluency performance. It is hypothesized that a discriminant function analysis will correctly classify 85% of cases, with naming and semantic fluency measures showing strong predictive power. Conclusions: The proposed findings aim to support the hypothesis that a combination of poor performance on the BNT and semantic fluency tasks, coupled with relatively intact phonemic fluency, is indicative of AD. These results have implications for early diagnosis and differentiation of AD from other dementias in clinical settings. Future research should aim to validate these findings in larger and more diverse samples to enhance the generalizability of these diagnostic markers. Additionally, longitudinal studies could provide insight into how these cognitive profiles evolve over the course of the disease, further informing early diagnosis and intervention strategies