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CAIDE Dementia Score and Cognition Association in Dementia-Free Hispanics from the HABS-HD Cohort
No full textBackground: Hispanics have a higher prevalence of cardiovascular risk factors compared to its non-Hispanic White counterparts. Studies have consistently shown a positive association between cardiovascular risk factors and cognitive decline. The Cardiovascular Risk Factors, Aging, and Incidence of Dementia risk score (CAIDE) predicts the risk of dementia later in life. CAIDE has been utilized in primarily non-Hispanic Whites. The aim of this study is to examine the relationship between CAIDE scores and cognitive function in Hispanics from the Health and Aging Brain Study (HABS-HD). We hypothesize that a higher CAIDE score will be associated with poorer cognitive performance in this cohort. Methods: Data from 1116 dementia-free Hispanic participants were analyzed. CAIDE was used as a predictor of cognitive performance on multiple cognitive domains. Cognitive scores were converted to Z scores, except for the MMSE, with lower Z scores meaning worse performance. CAIDE scores were used as a continuous variable; and were also categorized into two groups: low risk (CAIDE score < 9), and high risk (CAIDE score > 9). Linear regression was used to estimate the association between CAIDE and cognitive performance while adjusting for APOE4 status. Results: Sixty-eight percent of the total sample were female, mean age 61 (9.26), and 11 (4.54) years of education. Twenty-four percent of the sample were APOE4 carriers. Participants in the high-dementia risk group were older, had less years of education, higher systolic blood pressure and BMI compared to the low-dementia risk group. Cognitive performance was significantly lower in the high-risk group participants except for SEVLT delayed and FAS. Linear regression showed that CAIDE risk scores significantly predicted MMSE, Trails A, Trails B, and DSS, after adjusting for APOE4 status. Results did not change when using CAIDE as a binary variable. Conclusion: Our analysis suggests that higher CAIDE risk scores are associated with poorer performance in multiple cognitive domains. Further research is needed to validate the utility the CAIDE dementia score to predict cognitive decline in this population. This can aid targeted interventions to reduce dementia risk
Biodistribution of Reconstituted High-Density Lipoprotein Nanoparticles for Targeted Delivery to the Retina
No full textPoster Highlight: College of Biomedical and Translational Science, RAD 2025 Award Winning Posters & Oral PresentationsPurpose: Conventional ocular therapies have limitations, including, poor bioavailability, inadequate tissue penetration, and lack of target specificity. Nanoparticle-based drug delivery systems offer a promising approach for overcoming these challenges of ocular drug delivery. Our study evaluated the biodistribution and potential targeting of reconstituted high-density lipoprotein nanoparticles (rHDL NPs) loaded with near-infrared dye IR780 to retinal ganglion cells (RGCs) and optic nerve head astrocytes (ONHAs) as a model to mimic neuroprotective drug delivery in glaucoma. Methods: A stable rHDL-payload complex was formulated using IR780, phosphatidylcholine, and apolipoprotein A-I (Apo A-I) using a novel preparation method. Fluorescent rHDL (rHDL-IR780) was assessed for cellular uptake in primary human ONHAs in vitro, while scavenger receptor class B1 (SR-B1) expression was confirmed by western blot analysis. Receptor-mediated uptake was examined by SR-B1 receptor blocking. Ex vivo biodistribution was evaluated by intravitreal injection of rHDL into post-mortem human donor eyes. Results: Spectroscopic analysis confirmed IR780 encapsulation in rHDL NPs. Using immunoblot analyses, the expression of SR-B1 was detected in human ONHAs as well as in human retinal lysates. Blocking SR-B1 receptors significantly reduced IR780 uptake by ONHAs, supporting an SR-B1–mediated delivery mechanism. In ex vivo experiments, four hours post-injection, IR780 localized in the retinal nerve fiber and ganglion cell layers. By 24 hours, IR780 penetrated deeper retinal layers, and was taken up by RGCs, as seen by prominent labeling of RGCs with the IR780 dye. Conclusion: Our findings demonstrate that rHDL NPs facilitate targeted delivery to retinal tissues through an Apo A-I/SR-B1 pathway, overcoming ocular barriers to reach RGCs. This study supports the potential of rHDL NPs as a platform for neuroprotective drug delivery to treat glaucoma, enhancing both pharmacokinetics and targeted cellular uptake into RGCs
A Biorelevant in vitro Release Testing Method for Long-Acting Intraocular Injections
No full textIntroduction: Currently, there is no standardized in vitro dissolution method for intraocular injections. Furthermore, obtaining human pharmacokinetic (PK) data for intraocular injections is not possible. Accordingly, clinically relevant preclinical testing is crucial for these formulations. Here we utilize rabbit PK data of an in situ-forming intraocular implant to develop a novel biorelevant in vitro release method by matching the hydrophobicity of the release media to the ocular tissue. In addition, we developed a vitreous humor substitute with the capability to modulate its hydrophobicity as measured by contact angle. Methods: New Zealand white rabbits were used to obtain PK data of a novel compound formulated for intraocular injection. The drug was dissolved in dimethyl sulfoxide with and without polylactic-co-glycolic acid to create immediate-release and extended-release formulations. The formulation was injected into the vitreous space. At set timepoints, the animals were sacrificed and vitreous humor and retina (the target tissue) isolated and analyzed via LCMS for drug concentration. A series of synthetic vitreous humor substitutes were made using different ratios of hyaluronic acid (HA) and polyvinyl alcohol (PVA) in phosphate-buffered solution. Homogenized retina and vitreous humor were used to create a thin film of tissue on glass slides via casting followed by air drying. The water contact angles of the tissues were measured using an optical goniometer (OCA25, DataPhysics). The synthetic vitreous humor composition with a hydrophobicity most similar to rabbit vitreous humor was used as the starting media for the in vitro release test of the extended-release formulation. Results: The immediate-release PK study showed 3% of the drug remained in the retina and vitreous humor 45 minutes post injection. Concentration at 9 days in retina and vitreous humor was 0.3% and 5% respectively and was still detectable at 16 days. The in-situ implant study measured concentrations at days 1, 15, and 30. Retina concentrations were 3.5%, 10.4%, and 0.1% respectively. Concentrations in vitreous humor were 11.7%, 13.9%, and 0.3% respectively. Measured contact angle of synthetic vitreous humor increased with the ratio of PVA to HA. Contact angle for animal tissues was affected by sample processing. A washing protocol was added to remove solid structures before casting and was a crucial step to obtaining consistent contact angle measurements. Conclusions: Our goal is to improve the biorelevance of in vitro release testing methods for intraocular injections. We can obtain contact angles of ocular tissues with appropriate sample processing to remove soluble materials. Furthermore, a synthetic vitreous humor consisting of HA and PVA can be modulated to match the hydrophobicity of ocular tissues for biorelevant in vitro release testing
Exploring Mechanisms of an RGS12 variant: Implications for Bipolar Disorder
Full text linkSince bipolar disorder (BD) was first clinically described, significant strides have been made in understanding its genetic and neurobiological underpinnings. However, these insights have yet to yield objective biomarkers or fully effective treatment strategies. The diagnosis and management of BD remain highly challenging due to its complex etiology, diverse clinical presentations, and reliance on subjective symptomatic assessments. Current pharmacological interventions, including lithium, are fraught with limitations such as a narrow therapeutic index and potential teratogenic effects, restricting their long-term viability for many patients. Despite the strong heritability of BD, the precise molecular mechanisms contributing to its pathophysiology remain poorly understood, further complicating efforts to develop targeted therapies. Recognizing the critical need for a deeper molecular understanding of BD, this dissertation focused on elucidating the functional consequences of the R59Q variation in the RGS12 PDZ domain, a genetic factor implicated in BD susceptibility. By integrating in silico and in vitro methodologies—including molecular docking, molecular dynamics (MD) simulations, co-immunoprecipitation, and Surface Plasmon Resonance (SPR)—this study aimed to characterize the mutation's impact on RGS12 function and its potential role in dopamine signaling dysregulation and alteration of synaptic plasticity. Moreover, this dissertation builds upon prior research, particularly studies from the Siderovski Lab, which have established RGS12's pivotal role in dopamine regulation. Given that methylphenidate primarily targets norepinephrine pathways, its continued use in BD-ADHD patients appears justified, as it is unlikely to further perturb dopamine signaling mechanisms. This study also challenges the previous classification of RGS12 as 'undruggable' by demonstrating the development of novel small-molecule inhibitors. These inhibitors hold promise as adjuvants to existing opioid analgesics, with the potential to mitigate euphoria and reduce addiction liability. This dissertation explores the broader application of 'drug target and drug discovery' technologies including the use of a nanosensor-based SPR platform for biophysical target validation. These technologies present an opportunity for identifying novel therapeutic targets to address complex and 'undruggable' diseases, and develop more effective and safer drugs by precisely targeting disease-related proteins
Empty Nose Syndrome Following Nasal Surgery: A Scoping Review of Current Evidence
No full textBackground: This scoping review examines the existing literature on the incidence of Empty Nose Syndrome (ENS) following nasal surgery. The goal of this review is to explore the available evidence in order to highlight knowledge gaps and provide an overview of current findings regarding different nasal surgeries implicated in the development of ENS. Methods: A comprehensive search was conducted using PubMed, Scopus, and Embase Library, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews. For this review, relevant articles in the English language, up to the year 2024, were considered; it included studies analyzing the incidence and contributing factors of ENS after different nasal surgeries. Eligible studies investigating ENS development post-surgery included in the review encompassed cohort, case-control, and cross-sectional studies, in addition to case reports, case series, and clinical trials. After studies were selected, information regarding the type of study, surgeries performed, method of diagnosis, and functional postoperative outcomes were collected. Results: A total of 548 articles were identified. After duplicate removal, screening, and full-text review, 38 articles were included for analysis. The Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) was increasingly used in more recent studies, reflecting a trend toward uniform assessment of ENS. In addition, the most common surgical procedure related to ENS development was inferior turbinate reduction; other procedures such as radical turbinate resection, middle turbinate resection, and septoplasty were implicated. Conclusions: ENS development has been associated with multiple surgical interventions. However, additional studies using the ENS6Q investigating the development of ENS post-surgery are needed to better evaluate incidence rates and provide an understanding of the impact of various nasal surgeries in the development of this condition
Examining In-House Psychiatric Services in Fort Worth Public Schools
No full textPurpose: Within the past decade, Texas has seen a 38% increase in feelings of sadness or hopelessness among youth. When given a choice on the setting where they received mental health services many children preferred the school setting—a place of familiarity. As such, there has been a push to incorporate on-site behavioral health programs into the school setting. The purpose of this study is to illustrate the demand for in-house psychiatric services using data from the Eastern Hills Clinic. Methods: This study utilizes a retrospective chart review to examine patterns seen in the psychiatric patients at the Eastern Hills School-Based Clinic. Results: Between November of 2023 and June of 2024, the Eastern Hills SBHC has seen 9 psychiatric school-aged patients, with 30% being ages 0-10 and 70% being ages 10 and older. Of the students seen in the clinic, 86.9% are insured under Medicaid and the remaining 13.1% are uninsured. Patients seen in the clinic had an average of 3 unique diagnoses, with the most common diagnosis being unspecified anxiety disorder. Conclusion: Based on these findings, the need for the Eastern Hills SBHC is evident. The students receiving psychiatric care have seen positive outcomes, such as improvements in attendance, academic performance, and mood. Future directions for the clinic include early identification of student behavioral health issues and working with school professionals to navigate student diagnoses in an academic setting
Long-Term Impacts of Recurrent Adhesive Capsulitis on Acute Shoulder Injury
No full textRAD 2025 Award Winning Posters & Oral Presentations, Poster Highlight: Texas College of Osteopathic Medicine - Case StudyBackground: Adhesive capsulitis, or frozen shoulder, is a condition that can lead to long-term structural and biomechanical changes in the shoulder. It affects approximately 2% to 5% of the general population, with a higher prevalence in individuals aged 40 to 60 years, particularly women. Adhesive capsulitis is usually described as a self-limiting condition progressing through painful, stiff, and recovery phases. However, recent evidence suggests that some patients experience persistent functional limitations for years. These changes may predispose individuals to new onset shoulder injuries, which can exacerbate pain and functional deficits. Understanding this relationship is critical for developing targeted management strategies for older adults with a history of adhesive capsulitis. Case Information: A 67-year-old male with a history of left shoulder adhesive capsulitis in 2003 and right shoulder adhesive capsulitis in 2015, presented with acute onset left shoulder pain and reduced range of motion (ROM) following an overhand tennis serve. The patient reported that his previous left-sided adhesive capsulitis was treated with a corticosteroid injection with minimal relief. The right-sided adhesive capsulitis in 2015 resolved after a combination of early-onset physical therapy and NSAIDs. At this presentation, the patient described difficulty with overhead activities and limitations in both internal and external rotation. On physical examination, internal and external rotation ROM was mildly reduced, with 5/5 strength preserved across all muscle groups. Acute tenderness was localized to the tendinous portion of the left subscapularis muscle, consistent with tendinitis. Lift-off and Neer impingement tests were positive, supporting subscapularis involvement and possible subacromial pathology. However, no acute structural pathology was identified to explain the internal rotational deficit, suggesting that the observed limitations may be partially attributable to long-term biomechanical changes from prior adhesive capsulitis. Management included nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, and osteopathic manipulative treatment (OMT), which led to some improvement. Conclusions: This case highlights the potential for long-term effects of adhesive capsulitis to predispose individuals to functional deficits and impaired recovery following acute shoulder injuries. Chronic biomechanical adaptations and soft tissue changes from prior adhesive capsulitis may influence the presentation and recovery of new injuries. Further research is needed to explore the relationship between adhesive capsulitis and subsequent shoulder injuries, as well as to develop effective strategies for mitigating these long-term impacts
Membranous Web Esophageal Atresia Without a Tracheoesophageal Fistula
No full textBackground: Esophageal atresia (EA) due to a membranous web without tracheoesophageal fistula (TEF) is a rare congenital anomaly not included in the standard Gross taxonomy of EA. Only 10 cases previously have been reported. While some reported cases have associated anomalies, the frequency and type of anomalies do not seem to fall within the typical VACTERRL spectrum associated with classic EA. The vast majority of associated anomalies described are gastrointestinal in origin. Case presentation: a full-term infant presented with congenital esophageal obstruction secondary to a membranous web at the gastroesophageal (GE) junction associated with anorectal malformation with a membranous web obstructing the anus. The anal membrane was perforated at bedside with restoration of defecation. EA was corrected through laparotomy, longitudinal esophagogastrotomy, mucosal membrane excision, and transverse esophagogastroplasty. Bronchoscopy was performed concomitantly to rule out TEF. Oral feedings were restored, and the patient was discharged home on day of life 24. The infant developed episodic choking and apnea when lying flat 5 weeks post repair secondary to oropharyngeal dysphagia and persistent esophageal dysmotility despite improved esophageal dilation and patent GE junction repair. Conclusion: EA secondary to membranous web without TEF is a rare variant; surgical correction varies based on anatomic location of the esophageal web, infant size and presence of associated congenital intestinal anomalies. Long term esophageal dysphagia may result from persistent esophageal dilation and dysmotility
Accounting for cultural implications during pregnancy in the USA: a case report
No full textBackground: Intracranial aneurysm during pregnancy is at an increased rate of rupture during labor and delivery due to a 50% increase in cardiac output. As a result, neurology must be present during the labor and delivery to monitor the aneurysm. Case Presentation: A woman of African descent presents during her pregnancy to the emergency department at 29 weeks gestation for a severe headache and was diagnosed with an intracranial aneurysm. The hospital neurologist recommended taking precautions during labor due to the high intracranial pressures associated with pushing. After informing her obstetrician of her diagnosis, the patient was then told that they could not allow her to deliver at their hospital since there was not a neurologist to monitor the aneurysm during labor and delivery. Prior to this appointment, the patient had missed several pre-natal appointments due to traveling to visit family that lived out of state. The patient’s culture dictates that they stay connected to the community throughout pregnancy to guard and protect her pregnancy. The patient was informed by her obstetrician to call a high-level care hospital nearby that used her insurance to plan for her labor and delivery. Conclusions: We discuss cultural values that impact the patient’s pregnancy and analyze the need for research on care coordination across state lines in the US. We assess the potential implicit bias this patient may have faced and examine the impact these biases have on overall patient outcomes in the US
Early life functional transitions impact craniofacial morphology in osteogenesis imperfecta
No full textEarly life behaviors have a profound role in shaping adult craniofacial morphology. During early life, all mammals undergo the dynamic transition from suckling to mastication, a period coinciding with rapid cranial biomineralization. Osteogenesis imperfecta (OI), a genetic disorder that impacts the production of type I collagen, disrupts biomineralization, leading to craniofacial growth differences affecting quality of life. This study investigates craniofacial development during infant oral motor developmental stages in OI mice compared to unaffected wild-type littermates (WT mice). We hypothesize OI mice will exhibit smaller overall size, and the adult OI phenotype will develop postnatally in response to masticatory loading. Point cloud and fixed landmarks were collected from micro-computed tomography scans, then geometric morphometric analyses and interlandmark distances (ILDs) compared craniofacial size and shape between OI and WT mice at birth (P0; n = 27 OI murine/20 WT) and postnatal Days 7 (P7; n = 21/21), 14 (P14; n = 16/20), 21 (P21; n = 20/26), and 28 (P28; n = 26/33). This study found no size and shape differences between genotypes at birth. Starting at P7, OI mice are significantly (p < 0.05) smaller and display pronounced shape changes (p < 0.001) characterized by a larger neurocranium and a shorter viscerocranium. At P21, significant differences emerge in cranial base orientation, neurocranial width, viscerocranial shortening, and zygomatic arch displacement. These findings underscore the importance of early life oral motor stages in developing the adult OI craniofacial phenotype and oral health, suggesting earlier craniofacial interventions may improve effective treatment of OI.National Science Foundation,Grant/Award Number: #2236027;University of North Texas Health ScienceCenter: Preclinical Imaging Core PilotGrant; University of North Texas HealthScience Center: Department of Physiologyand Anatomy Seed Gran