University of North Texas
UNTHSC Scholar (University. of North Texas Health Science Center)Not a member yet
6724 research outputs found
Sort by
The Prodrug DHED Delivers 17beta-Estradiol into the Retina for Protection of Retinal Ganglion Cells and Preservation of Visual Function in an Animal Model of Glaucoma
Get PDFWe report a three-pronged phenotypic evaluation of the bioprecursor prodrug 10beta,17beta-dihydroxyestra-1,4-dien-3-one (DHED) that selectively produces 17beta-estradiol (E2) in the retina after topical administration and halts glaucomatous neurodegeneration in a male rat model of the disease. Ocular hypertension (OHT) was induced by hyperosmotic saline injection into an episcleral vein of the eye. Animals received daily DHED eye drops for 12 weeks. Deterioration of visual acuity and contrast sensitivity by OHT in these animals were markedly prevented by the DHED-derived E2 with concomitant preservation of retinal ganglion cells and their axons. In addition, we utilized targeted retina proteomics and a previously established panel of proteins as preclinical biomarkers in the context of OHT-induced neurodegeneration as a characteristic process of the disease. The prodrug treatment provided retina-targeted remediation against the glaucomatous dysregulations of these surrogate endpoints without increasing circulating E2 levels. Collectively, the demonstrated significant neuroprotective effect by the DHED-derived E2 in the selected animal model of glaucoma supports the translational potential of our presented ocular neuroprotective approach owing to its inherent therapeutic safety and efficacy.This work was supported by the National Eye Institute (National Institutes of Health (NIH), Bethesda, MD, USA, grant number EY027005 (K.P.-T.) and by the Robert A. Welch Foundation (endowment BK-0031 to L.P.). A.K. was also supported by the Neurobiology of Aging and Alzheimer's Disease Training Grant (NIH T32 AG020494 to N.S.)
Navigating an Acute presentation of HIV/AIDS on a Young Adult
No full textBACKGROUND: The initial stage of human immunodeficiency virus (HIV) infection can resemble mononucleosis, showcasing various nonspecific symptoms. Due to its elusive nature, clinicians may overlook the diagnosis without a heightened level of suspicion. Common clinical symptoms: fever, sore throat, skin rash, lymphadenopathy, myalgia/arthralgia, diarrhea, weight loss, night sweats, headaches. Opportunistic infections occur with CD4 counts < 200 cells/microL. We will be discussing Cryptococcus.
CASE INFORMATION:
HPI: A 27 y.o. Male with no past medical history comes to the emergency department with a chief complaint of headache and abdominal pain. Pt states that the pain and headache began about 3 weeks ago and has been worsening.
The headache is diffuse but worse in the back of the head. Pt admits to feeling worse at night, having night sweats, subjective fevers, N/V, weight loss and decreased appetite. Pt denies photosensitivity, chest pain, dyspnea, and body aches.
Social: Pt denies IVDU, endorses heavy drinking, THC use, currently engaged in MSM.
PE: Ill-appearing, occipital tenderness to palpation, no nuchal rigidity, diffuse maculopapular rash across the forehead.
Labs: WBC 3.7-5.1; AST 38; ALT 65; UA neg; UDS THC and Opioids; HCVAB +; HIV screening +; HIV RNA PCR = 108k copies; CD4 = 33.
CSF: Cryptococcal anti-gen+ (1:2560) titer; Clear, Colorless; WBC 239/cc (ref 0-5); Lymphocytes 97% (ref 20-50%); RBC 3653/cc (ref 0-5); Glucose: 42 (ref 40-70); Protein: 42.9 (15-45); OP: 57 cm H20 (very high)
Imaging: CT Chest showing a single LUL Cavitary lung lesion
Assessment: Cryptococcal Meningitis Opportunistic Infection 2/2 HIV/AIDS
Treatment: Amphotecirin B (3 to 4 mg/kg IV per day); Flucytosine (100mg/kg q6h). Regimen recommended for minimum of 2 wks – may extend to 4-6 wks
RESULTS: After nine days of hospitalization, the patient disclosed a history of engaging in HIV high-risk behaviors and activities. This revelation prompted medical attention towards HIV testing and further evaluation. However, challenges arose during attempts to perform bedside lumbar puncture, leading to the decision to obtain the procedure through Interventional Radiology (IR). Following the diagnostic procedures, including HIV testing and assessment of CD4 counts, opportunistic bacterial tests were ordered to address potential complications. Subsequently, appropriate treatment was administered based on the test results, ensuring comprehensive care for the patient's condition.
CONCLUSIONS: Physicians should have a low threshold for suspicion for HIV. Give priority to early detection and proactive management to enhance patient outcomes. The absence of a history of risky behavior or activities should not deter a physician from pursuing an HIV diagnosis. An effective way to gather HIV-related risk factors is by obtaining the patient's history in a one-on-one setting. The lack of HIV testing resulted in complications and prolonged hospitalization, ultimately leading to the patient's death secondary to seizures and respiratory failure
Breaking Barries, Building Bridges: Advancing Interprofessional Collaboration through Pediatric Critical Simulation
No full textResearch Appreciation Day Award Winner - Texas College of Osteopathic Medicine, University of North Texas Health Science Center, 2024 Interprofessionalism AwardFacilitating exposure of interprofessional collaboration in healthcare is a critical approach to fostering a seamless transition from academics to professional practice. In response, we present a collaborative effort between the student leaders of the Student Society of Health-System Pharmacists and the Texas College of Osteopathic Medicine (TCOM) Simulation Initiative for Medical Simulation (SIMS). Past research conducted at this university has identified the benefits of conducting interprofessional critical care simulation events between groups of student physicians and student pharmacists. During this third iteration of interprofessional simulation events, teams of student pharmacists and physicians worked together utilizing the Pediatric Advanced Life Support (PALS) algorithms to manage simulated medical emergencies of pediatric patients. The simulated cases included ventricular tachycardia and a critical condition status post-drowning case.
The two main objectives of the collaboration included our primary objective of improving communication and teamwork skills through collaborative management of simulated pediatric medical emergencies. Our other key objective was enhancing the clinical decision-making abilities of student pharmacists and physicians. Specifically, how students can utilize the strengths of the other profession to help overcome the unique challenges presented during a simulated pediatric critical care scenario.
We assessed our objectives by having our participants complete a pre-and post-simulation survey with unique questions for the student pharmacists and physicians. Each question was tied back to a primary concept and contained a 5-point Likert Scale statement. The responses were analyzed using a two-sided, unpaired T-test to determine the significance between our pre and post-survey results.
A total of 48 students participated in the simulation event; 34 student physicians and 14 student pharmacists. These students were broken up into teams of 2-3 student pharmacists working collaboratively in teams with 5 student physicians. Each team utilized the PALS algorithms to manage the simulated cases. All ten student physicians and all four student pharmacist questions had an increase in average response when comparing our pre- and post-simulation surveys. However, due to a decrease in post-survey responses and our small sample size, six out of ten student physician questions and none of our student pharmacists questions had a statistically significant difference (p<0.05). Future studies incorporating a larger sample size and additional interprofessional professions may improve the statistical limitations. This study showed a significant improvement in student physicians’ understanding of pharmacists’ roles in critical scenarios. Specifically, this improved a better understanding of protocol timings involved in managing critically ill pediatric patients. The primary concepts that showed an improvement in this study included interprofessional communication, confidence in the ability to manage a critical care scenario, and the importance of an interprofessional approach to patient care.
This study expanded upon past research which demonstrated the benefits of interprofessional educational simulations, by focusing on a special population; pediatrics. Increasing interprofessional collaboration in future simulated events, especially in special populations will undoubtedly broaden student knowledge and foster a seamless transition to professional practice
EXPLORING A COMBINATION USING CHEMOTHERAPY AND TOLFENAMIC ACID TO INDUCE ANTI-PROLIFERATIVE RESPONSE IN MEDULLOBLASTOMA CELL LINES
No full textBackground: Medulloblastoma (MB) is the most common malignant brain tumor in children, with a peak incidence between the ages of 5-9 years old. Originating in the cerebellum, it often metastasizes throughout the CNS via the CSF, making it very difficult to treat. Current treatment options are limited, and includes surgical resection followed by radiation and chemotherapeutic agents. However, these agents are associated with numerous toxicities and long-term neurocognitive deficits in survivors. Our laboratory is interested in identifying drug resistance cell markers and combination therapies that target them to help increase efficacy of the chemotherapeutic agents. We have previously demonstrated that combination therapy of chemotherapeutic agents with Tolfenamic acid (TA), decreased the number of viable cancer cells when compared to the chemotherapeutic agents alone. TA is a non-steroidal anti-inflammatory drug, and its anti-cancer activity can be attributed to its ability to downregulate Specificity Protein 1 (Sp1), a transcription factor responsible for the upregulation of the anti-apoptotic protein, Survivin. Numerous cancerous tumors have been known to express high levels of Sp1 and SurvivIn, however these markers have not been well established in MB. Purpose: The aim of the project is to elucidate the association of Survivin expression in MB cells with the likelihood of patient survival and to test combination treatments of chemotherapeutic agents with the potential Survivin inhibitor, TA. The goal is to reduce the effective dosage of the chemotherapeutic agent Cisplatin, thereby reducing their side effect profiles. Methods: A R2 genomics visualization platform was accessed to obtain data regarding patient survival rates and Survivin expression in MB cells. A Kaplan-Meier curve was then generated to analyze the relationship. MB cell lines, DAOY, and D283 cells were obtained through the ATCC and cultured following standard cell culture conditions. Cells were then treated with vehicle (DMSO) or optimized doses of a chemotherapeutic agents (Vincristine or Cisplatin) with TA. Cell viability was measured at 24h and 48h post-treatment using Cell-TiterGlo kit (Promega) following manufacturer’s instructions. Results: The Kaplan-Meier curve showed that the overexpression of Survivin resulted in a poor prognosis and low survival rates among MB patients. Compared to results of MB cell inhibition with individual agents (Vincristine and Cisplatin) from our previous studies, the combination of TA and Vincristine or TA and Cisplatin showed decreased MB cell growth and downregulation of Survivin. Differential effects of Vincristine and Cisplatin were noted against DAOY and D283 cell lines. Conclusion: These preliminary observations suggest that Survivin expression may be associated with poor prognosis in MB patients and that inhibiting Survivin with TA is inducing the anti-proliferative effects of chemotherapeutic agents in MB cells. Further research involving other chemotherapies is required to understand TA’s role in Survivin inhibition. Understanding the specific effect of Cisplatin can help to design the therapies based on the molecular sub-group of MB.Partially funded by a grant from the Cancer Prevention and Research Institute of Texa
Discussion on Treating Pyelonephritis and Borderline Sepsis on Medical Mission Trips
No full textDiscussion on Treating Pyelonephritis and Borderline Sepsis on Medical Mission Trips
Bianca Garcia OMS-II, Jordan Thompson OMS-III, Lesca Hadley, MD
The Texas College of Osteopathic Medicine, UNT Health Science Center, Fort Worth, TX; Antigua, Guatemala Medical Mission
Introduction:
The case report discusses the diagnosis and management of pyelonephritis while on a DOCARE medical mission trip in Guatemala. Pyelonephritis is a common and very treatable diagnosis in the United States due to easy access to resources and physicians. This case is unique because it discusses the specific challenges providers faced not only managing but diagnosing the disease due to limited resources and lack of follow up care. The goal of this case report is to demonstrate the unique obstacles providers faced while working on a medical mission trip.
Case Summary
The patient was a 27 yo female who presented to the clinic with nonspecific complaints of pelvic pain and 3 days of dysuria, polyuria and thick/yellow discharge. Upon arrival at the clinic, the patient had a BP of 115/70, pulse 91 and a temperature of 100.7. Urinalysis demonstrated moderate leukocytes and negative pregnancy test. Physical exam demonstrated negative CVA tenderness. The differential for the patient remained UTI vs pyelonephritis. The patient’s temperature and pulse met 2/4 SIRS criteria which was concerning for a more serious infection such as pyelonephritis. However, the lack of CVA pointed more towards UTI. Making a treatment planned posed challenges because without a leukocyte count or blood cultures there was no way to confirm pyelonephritis. Providers knew that it was unlikely for the patient to receive follow-up care if the infection were to progress. Due to this, it was elected to choose a more aggressive treatment for pyelonephritis with 500mg ciprofloxacin BID for 14 days and instructions to find a hospital if symptoms worsen.
Conclusions
In the village of the DOCARE clinic, only 10% of the village has access to health care. The closest public clinic is 1.5 hours away and hospital is 2 hours away. Based on literature review, the standard of care for pyelonephritis would include of larger workup with blood cultures to guide antibiotic choice and close monitoring and follow-up of the patient. This standard of care was not available in Guatemala. Understanding of the resources available to the patient was a key factor in choosing a more aggressive treatment for the patient
Dyslipidemia in Hispanic Prediabetics with Mild Cognitive Impairment
No full textPurpose: Prediabetes or impaired glucose tolerance affects an estimated 96 million adults in the United States and may be a modifiable risk factor for cognitive impairment. Several studies have shown that prediabetics experience poorer longitudinal cognitive outcomes compared to non-diabetics; however, the exact mechanism is still a matter of debate. Furthermore, prediabetic patients often experience metabolic syndrome-related comorbidities like dyslipidemia that may be related to in the development and progression of cognitive impairment in prediabetic patient populations. The aim of this study was to examine the relationship between lipid levels between ethnic groups in prediabetic, mildly cognitively impaired, Hispanics, Non-Hispanic Whites, and African Americans. Methods: Data from 144 mildly cognitively impaired prediabetic participants (Hispanics, Non-Hispanic Whites, and African Americans) was collected and analyzed from the Health and Aging Brain Study: Health Disparities (HABS-HD), a community-based epidemiological study of aging. Participants of the study undergo cognitive and functional testing, as well as brain imaging (MRI and PET). Basic demographic information is also collected, and blood samples are used to determine HbA1c, fasting blood glucose, and lipid profiles. One-way ANOVAs examined differences in total cholesterol, triglyceride, and LDL measurements based on ethnicity. Results: Results showed significant differences in total cholesterol levels between the Hispanic (M = 193.98, SD = 38.17), non-Hispanic white (M = 169.54, SD = 37.26), and African American (M = 170.41, SD = 35.52) populations (F = 7.20, p <0.001), triglyceride levels between the Hispanic (M = 154.25, SD = 80.47), non-Hispanic white (M = 124.62, SD = 50.81), and African American (M = 95.17, SD – 57.77) populations (F = 10.96, p<0.000), and LDL levels between the Hispanic (M = 111.86, SD = 31.88), non-Hispanic white (M = 95.62, SD = 29.91), and African American (M = 94.77, SD = 27.38) populations (F = 5.37, p<0.006). Conclusion: Prediabetic Hispanic participants in the study with MCI were shown to have higher lipid profiles (triglycerides, LDL, and total cholesterol) as compared to non-Hispanic white and African American participants. Future studies should further examine the relationship between prediabetes and dyslipidemia, including clinical outcomes regarding the treatment of elevated lipids.National Institute on Agin
Impact of sex and hypoxia on brain region-specific expression of androgen receptor AR45 and G protein Gαq in young adult rats
No full textPurpose: Sex differences in oxidative stress-associated cognitive decline are influenced by sex hormone levels. However, little is known regarding the expression of hormone receptors in brain regions associated with cognitive function. Notably, oxidative stress-associated neuronal cell death is exacerbated through testosterone signaling via membrane-associated androgen receptor AR45 and G protein Gαq. The objective of this study was to elucidate the expression of AR45 and Gαq in brain regions associated with cognitive function. Additionally, we investigated whether chronic intermittent hypoxia (CIH), an oxidative stressor with sex-specific effects, would modulate AR45 and Gαq expression.
Methods: Adult male and female Sprague-Dawley rats were exposed to CIH or normoxia for 14 days. We quantified AR45 and Gαq protein expression in various cognition-associated brain regions [dorsal hippocampal CA1, CA3, DG, and entorhinal cortex (ETC)] via western blotting. For comparisons, AR45 and Gαq protein expression were also assessed in brain regions outside the hippocampal-ETC circuit [thalamus (TH) and striatum (STR)].
Results: The highest AR45 levels were expressed in the CA1 while the lowest expression was observed in the STR. The highest Gαq levels were expressed in the DG and ETC while the lowest expression was observed in the TH. We observed no effect of sex on AR45 or Gαq expression regardless of brain region assessed. Similarly, there was no effect of CIH on AR45 expression in any of the brain regions examined. However, CIH exposure increased Gαq expression only in the CA3 regardless of sex.
Conclusions: Our findings reveal enrichment of AR45 and Gαq protein expression within the hippocampal-ETC circuit, which is vulnerable to oxidative stress and neurodegeneration during cognitive decline. Moreover, our data suggest the CA3 is the most vulnerable region to CIH-mediated oxidative stress. Overall, these findings were observed in both sexes, indicating that there are no observed sex differences in AR45 and Gαq expression or their modulation by CIH.This study was supported by NIH R01 NS0091359 and UNTHSC Seed grant funding to RLC, AHA 22POST-903250 to JLB, AHA 22PRE-900431 to JJG, and NIH T32 AG020494 to SM
Increasing Cancer Genetic Referrals via Best Practice Alerts (BPA)
No full textBackground: Germline genetic testing (GT) is recommended for all patients (pts) with pancreatic cancer (PC). However, genetic referral (GR) rates for PC are low even at academic centers; there is a paucity of literature at safety-net hospitals (SNH) which often treat higher percentages of cancers at advanced stages. Providers focus on the challenging treatment of PC and may not prioritize GT referrals. Technology can be adapted to aid in this process. Best practice alerts (BPA) built in Electronic Medical Records (EMR) can prompt providers to place GR order. We initiated BPA at John Peter Smith (JPS) hospital, a SNH in Texas, and evaluated if the BPA improved referral patterns. Methods: A retrospective review was conducted using JPS tumor registry data. We studied pts diagnosed with pancreatic adenocarcinoma (AC) or neuroendocrine tumors (NET) from 1/1/2018 to 4/30/2023 at JPS. BPA go-live date was 10/19/2022. Data Analytics team queried EMR regarding GR, if pts completed their genetics encounter (GE), and GT. Statistical analysis using a two-tailed T test was performed. Results: 162 PC pts were identified: 155 (96%) AC and 7 (4%) NET, and the median age was 59 years. A majority of patients were diagnosed in house (114/162, 70%), while the rest were referred to JPS after diagnosis elsewhere. A total of 57 pts were excluded due to being placed on hospice, death within 3 months of diagnosis, or refusing oncology services at JPS. 105 pts were included for analyses: 96 were diagnosed with PC before the BPA go-live date (pre-BPA) and 9 after the BPA go-live date (post-BPA). 36 (38%) pts were referred pre-BPA. 23 pre-BPA pts completed GE, median of 15 days from referral. 7 out of 9 (78%) pts received GR post-BPA. Post-BPA pts were all referred due to BPA triggers being fired. 2 post-BPA pts completed GE with a median time of 27.5 days from GR. Since launching the BPA, a statistically significant increase in GR has been observed (p=0.0187). 2 pre-BPA pts who completed GT were found to have a pathogenic variant. Conclusions: BPA has shown a significant improvement in GR for PC. At the recent 2024 quarterly JPS Cancer Committee meeting, we found an update of considerable improvement in genetic referrals, with 83% of new pancreatic cancers receiving genetic referrals in 2023 compared to only 35% in 2022.Our study population is limited by rarity of PC, and the BPA alert is set to only fire for pts receiving oncology care at JPS. We noted a large number of pre-BPA pts that have yet to be referred and remain at risk. We plan to have a process to notify these pts’ providers to refer them to genetic testing. For future studies, we will analyze pts with other cancer diagnoses to continue to improve upon the GR process. Authors: Priyanka Reddy, Jacqueline Mersch, Melissa Howell, Jolonda Bullock, Brian Reys, Parker Read, Nitin Rajpurohit, Bassam Ghabach, Kalyani Narr
High expression of N-acetyl transferase 9 in cholangiocarcinoma and its possible role in tumor progression
No full textResearch Appreciation Day Award Winner - School of Biomedical Sciences, 2024 Department of Microbiology, Immunology & Genetics (Cell Biology, Immunology & Microbiology) Award - 2nd PlaceCholangiocarcinoma, CCA, is an aggressive type of liver cancer due to the scarce number of biomarkers and its resistance to anticancer drugs, leading to difficulty in its early detection. Its 5-year survival rate ranges from 2% to 24%, depending on severity and metastasis. Currently, surgery is the most effective treatment option, but only under certain criteria, such as the cancer being caught early and having not metastasized. CCA incidence is the highest in Asian countries because of the presence of a carcinogenic liver fluke. N-acetyl transferase, NAT, is an enzyme with many functions, including regulating protein stability, membrane targeting, gene silencing, and drug resistance. Different subsets of NATs are also known to be biomarkers for different types of cancer, such as colorectal, prostate, and breast cancers. According to The Cancer Genome Atlas database, NAT9, a subset of the NAT family, is overexpressed in patients with CCA; however, no studies have demonstrated its role in CCA, indicating the need for more research. In this study, we aim to assess the expression of NAT9 in CCA using cell lines and patient tissue samples through RT-qPCR, western blotting, and immunohistochemistry. This data will help us shed light on NAT9’s role in the tumorigenesis of CCA and could be a promising biomarker and therapeutic target for CCA
Identifying Training Needs for Informal Caregivers to Support Activity and Mobility for Community-Dwelling Individuals with Cognitive and Physical Impairments
No full textBackground: With the aging population and the rise in disabilities, there is a growing need for caregiving. In the United States, an overwhelming 83% of older adults receive support from family members, friends, or unpaid caregivers, with almost half of these caregivers aiding individuals with Alzheimer's or other types of dementia. As cognitive decline progresses to the middle and late stages, caregivers play an increasingly critical role in tasks such as feeding, bathing, transferring, and providing mobility assistance. However, informal caregivers usually lack the formal training that professional caregivers in care facilities undergo to carry out these tasks effectively. This study aims to hold focus groups to identify the needs of informal caregivers of persons with dementia in order to develop and deliver support training. Methods: Researchers conducted a focus group using members from a dementia caregiver support group. The specialists in dementia care and mobility worked together collaboratively to develop the topic guide. The guide aimed to explore participants' experiences with the physical and mental challenges of caregiving for persons with dementia. It also aimed to uncover the aspects of their care that held the greatest challenge and to identify areas for potential improvement in their care or condition. Results: A total of six participants were engaged in two focus groups. Through analyzing transcripts from these groups, several main themes have emerged: understanding how relationship influences the role of a caregiver, challenges regarding specific conditions and needs, mobility challenges, reliable strategies and resources, and the caregiver burden. Participants expressed the need for different options to include online and in-person training- with a potential need for individualized attention. Conclusions: The results of this study offer insights into research priorities in dementia care. These findings have played a crucial role in shaping the content of developing workshops and courses that aim to address the mobility and activity needs of the patient while considering their informal caregiver’s burden