University of North Texas
UNTHSC Scholar (University. of North Texas Health Science Center)Not a member yet
6724 research outputs found
Sort by
Efficacy of Using Zoledronate for Prevention of Craniofacial Fractures in Mice with Osteogenesis Imperfecta
No full textOsteogenesis imperfecta (OI) is a genetic disorder of type I collagen that results in increased bone fragility, increased fracture rates, and abnormalities of the limbs, vertebral column, and craniofacial skeleton. Long-lasting bisphosphonate drugs, like zoledronate, are used in children with OI to increase bone mineral density and prevent skeletal fractures. Zoledronate increases osteoclast apoptosis, thus reducing relative rates of bone resorption and increasing formation rates. Previous experimental research on the efficacy of zoledronate has focused largely on the postcranial skeleton (e.g. limbs). The goal of this study is to investigate if zoledronate reduces the rate of craniofacial fractures in mice with osteogenesis imperfecta. We hypothesize that mice treated with zoledronate will have fewer skeletal fractures of the skull compared to untreated mice.
Mice with OI (OIM, B6C3Fe a/a-Col1a2oim/oim) and unaffected littermates (wild-type, WT) were randomly assigned into either control (C) or zoledronate (ZOL) treatment groups (n=5/genotype/group). Mice treated with zoledronate received subcutaneous injections of the drug (80 µg/kg) at 4, 8, and 12 weeks of age. The craniofacial skeleton of all mice was imaged with a micro-CT scanner (20 µm3 voxels) every 4 weeks from 4-16 weeks. 3D models of the craniofacial skeleton were generated in 3D Slicer software, and analyzed for incidence and location of fractures.
At 8 weeks, no fractures were observed in WT-C or WT-ZOL mice. However, fractures were observed in both groups of OIM mice. 80% (4/5 per group) of OIM-C and OIM-ZOL mice had skeletal fractures, and the remaining 20% (1/5 per group) had fractured incisors. All skeletal fractures were observed along the zygomatic arch, proximal to the attachment site of the masseter muscle. Both unilateral and bilateral zygomatic fractures were observed.
Preliminary data indicates that a single treatment with zoledronate at 4 weeks of age does not reduce the incidence of craniofacial fractures in mice with OI. Additional data is needed to assess if zoledronate improves fracture healing or bone quality outcomes (e.g. BMD) in the craniofacial skeleton, as has been demonstrated in limb bones. Additionally, the prevalence of fractures proximal to skeletal attachment sites for feeding muscles suggestions that muscle-bone interactions are a key component for understanding the origin of facial fractures in this model. Previous work has shown that long-term use of bisphosphonates like zoledronate may have negative outcomes for the craniofacial skeleton, including delayed bone formation, altered dental eruption, and osteonecrosis of the jaw (ONJ). This study suggests that craniofacial health is an important consideration, distinct from postcranial health, when planning interventions for patients with OI.UNTHSC REAP Early Stage Investigator Gran
A Case of Gitelman Syndrome with an Uncommon Presentation of Normomagnesemia
No full textBackground: Gitelman Syndrome (GS), also known as familial hypokalemia-hypomagnesemia, is an autosomal recessive renal tubular disorder that impacts sodium retention to electrolyte imbalance. It is a rare salt-losing tubulopathy that has a 1:40,000 prevalence. The disorder is mostly associated with symptoms including hypokalemic metabolic alkalosis with hypomagnesemia and low urinary calcium excretion.
Case Information: An8-year-old female with a history of ADHD and bipolar disorder presents to her primary care clinic for initial concerns about low potassium and high cholesterol after getting routine lab work done outside of her primary care clinic. She had been receiving treatment at a mental health facility and had routine bloodwork done for her medications. The patient was referred to her primary care provider to follow up on the lab work. Her guardian had concerns about the child’s short stature and a bone age X-ray and labs were ordered. Her guardian also stated that her paternal grandmother had hypokalemia of unknown etiology. Her lab result showed hypokalemia (2.7 mmol/L) and hypercholesterolemia (192 mg/dL), so she was sent to a children’s hospital emergency room for immediate management. In the ER, the patient again had hypokalemia (2.5 mmol/L), elevated anion gap (21 mmol/L), and positive ketones. Her EKG showed prolonged QT interval and she was admitted to the hospital for further management. After receiving a potassium replacement, her EKG normalized, and the cardiologist cleared her for further follow-up. Genetic testing confirmed that she has Gitelman Syndrome, specifically a mutation in the SLC12A3 gene. Interestingly, Gitleman Syndrome usually presents with hypomagnesemia, but in this case, the patient only had hypokalemia and not hypomagnesemia. The patient was discharged with oral potassium and has been following up with a nephrologist on a regular basis.
Conclusions: This case study showcases a rare case of Gitelman Syndrome with an unusual presentation of normomagnesemia. Future research should be conducted to solidify diagnostic criteria, evaluate abnormalities, and assess the long-term effects of the disease
High school wrestler with episode of psychosis and self-harm following loss of consciousness event.
No full textResearch Appreciation Day Award Winner - Texas College of Osteopathic Medicine, 2024 Medical Student Government Association Best in Fourth Year ClassCase History: Patient was a 16-year-old male with a history of depression taking Prozac and ADHD taking Adderall. No previous history of psychosis. Patient presented in February 2023 for evaluation after an episode of LOC following a blow to lateral eye while wrestling. Patient regained consciousness after a few seconds, but reported difficulty with speech, gait, and inability to remember the incident in detail. Patient was taken to the emergency department and CT scan was negative for acute abnormalities. Patient presented 7-days post-incident with dizziness, light sensitivity, and cognitive slowing. At patient visit 1-month post-incident he reported resolution of dizziness and light sensitivity, but persistence of cognitive slowing. Between 1-month and 2-month post incident visits patient experienced episode of psychosis resulting in self-harm. Patient had no recollection of episode.
Physical Examination: In office patient was well appearing with no sign of distress. Neck was nontender and supple with full ROM and no bony tenderness. Negative spurling test. No increased work of breathing. Heart sounds normal. No bruits present on auscultation of neck. Alert and oriented with normal mentation and speech. No motor or sensory deficits present. Negative dysmetria, dysdiadochokinesia, pronator drift, Romberg. No evidence of bruising or bony abnormalities to either orbit. Pupils were PERRLA with EOMI. Vertical and horizontal saccades present bilaterally with provocation of symptoms. Normal mood and affect with clear and logical thought processes.
Differential Diagnosis #1: Concussion
Differential Diagnosis #2: Orthostatic syncope
Differential Diagnosis #3: Post traumatic migraine
Differential Diagnosis #4: Subdural hematoma
Differential Diagnosis: Chronic fatigue syndrome
Tests & Results: Testing performed 7-day post-incident; VOMS: saccades horizontal 9 and vertical 9. C3 Logic Data: symptoms severity 15of 27, SAC 20, BESS abnormal with 44 errors, trails A 78.3, trails B 93.3. Testing performed 28-day post-incident; VOMS: saccades horizontal 12 and vertical 11. C3 Logic Data: symptoms severity 17of 27, SAC 26, BESS abnormal with 11 errors, trails A 18.1, trails B 41.6.
Final/Working Diagnosis: Psychotic episode with self-harm secondary to concussion.
Discussion: Literature suggest mild traumatic brain injuries can trigger initial psychotic episodes in adolescents and adults. This case demonstrates a possible psychotic episode triggered by a TBI due to a concussion. In addition, the risk of trigger may be greater in adolescents with a pre-existing psychiatric diagnosis. Further analysis and research are necessary to evaluate a possible connection between the frequency of psychiatric symptoms following a concussion in adolescents with and without prior psychiatric diagnosis. This information may help identify at risk individuals and help guide prophylactic treatment to prevent psychiatric symptoms from occurring in the post-concussive period.
Outcome: Following the psychotic episode patient saw a psychiatrist and medication for MDD was changed from Prozac to Abilify. The patient was stable on this medication regimen at his 2-month follow up visit. At this time patient report 98% improvement from original symptoms and had returned to physical activity and full days at school. He was cleared for full-activity and advised to follow up as needed
Expansion Microscopy for Super-Resolution Imaging of the Rodent Brain
No full textExpansion Microscopy for Super-Resolution Imaging of the Rodent Brain
Hannah Ampofo, Raymond Berry, Claire Spann, Ran Liu, Shaohua Yang
Pharmacology and Neuroscience Department, School of Biomedical Sciences, University of North Texas Health Science Center, Texas, United States.
Purpose-To establish Expansion microscopy (ExM) for super-resolution imaging of the rodent brain.
Background- ExM is a remarkable imaging technology that enables nanoscale resolution in three-dimensional (3-D) imaging of preserved cells and tissues. ExM, which was invented in 2015, physically expands specimens using a hydrogel, allowing high-resolution imaging to be done with conventional diffraction-limited microscopes. The basic idea is to attach anchors to biomolecules or labels chemically and link them to a hydrogel that is uniformly distributed throughout the material. This polymerization technique separates biomolecules while maintaining their spatial organization by enabling isotropic expansion. The procedure is similar to sketching an outline on an inflating object and blowing it up: the ink particles will move apart, but their relative organization remains the same. Traditional optical imaging is unable to resolve nanoscale structures with dimensions smaller than 200–300 nm due to the fundamental physical limitations imposed by diffraction. ExM offers faster imaging speeds as compared to super-resolution methods, and enhanced antibody efficiency due to the decrowding effect generated by expanding biomolecules. The original ExM could resolve the specimen at 70 nm, however, new variants such as iterative ExM, 10X ExM microscopy, and nine-fold microscopy can resolve down to 15 to 30 nm, comparable to super-resolution microscopes.
Method- The Paper-MAP version of expansion microscopy, a modified MAP method that allows immunostaining and expansion within two days was employed. The procedure involved staining floating mouse brain sections and incubating with a Paper-MAP cocktail (consisting of TEMED and sodium acrylate) and ammonium persulfate solution. The hydrogel matrix was created in situ through the crosslinking of sodium acrylate and bisacrylamide, forming a dense polyelectrolyte hydrogel. A denaturing solution was used to mechanically homogenize the sample and then expanded using deionized water. The pre and post-expanded sections were imaged using a Zeiss LSM 510 confocal microscope.
Results- Following the addition of the monomer solution, the expansion procedure produced a 2 fold increase in size. This was followed by an evident 4 to 5 fold increase after the expansion was completed. We compared the pre-expansion image to the post-expansion image and observed intricate and detailed structures with significantly enhanced resolution that were previously indistinguishable in the pre-expansion section using confocal microscope.
Conclusion- Expansion microscopy is a versatile and accessible imaging technique that resulted in significant improvements in imaging the microscopic configuration of the mouse brain. Its broad application offers a powerful tool for biological research in diverse organisms.NI
Perceived Advantages and Disadvantages of Clinical Trial Participation Among Minority communities: Results from a cross-sectional survey
No full textAuthors: Sharon John,Marley Arnaud, Uyai Ibanga, Destiny Grisby, & Madison Townsend
Institution worked with: University of Houston, Humana Institute
Purpose: Research has shown that clinical trial results and safety may not be inclusive of minority populations (Nazha). The consequences include reduced generalizability of findings that might lead to adverse effects for unrepresented groups. Unrepresented clinical trials not tested with diverse populations could widen the gap within healthcare disparities. However, it is important to acknowledge and address the unethical practices of the past to understand the hesitancy of certain groups’ involvement. There is a need to evaluate the current perception of clinical trial involvement of minority groups and use the results to diversify clinical trial recruitment. This research explores the general population’s perspective on participating in clinical trials and evaluates results by separate racial groups. What are the perceived advantages and disadvantages of participating in clinical trials for minorities?
Methods: The survey represents Black or African American, American Indian or Alaska Native, Hispanic or Latino, and Caucasian participation in the study. The inclusion criteria for participants are adult (18+) and English-speaking. The research study was conducted using an online cross-sectional and gathered a total of 736 respondents.
Results: The data shows the differences in perceived advantages and disadvantages of participating in clinical trials between white, black, and other races. The Caucasian population is 1.7x times more likely than minority groups to consider participating in clinical trials as an advantage. The top three advantages of clinical trial participation for minoritized populations are: "doing something positive for self" with 34% agreement, "getting a cash stipend" with 34%, and doing something that will help others with 28%. The top three disadvantages of clinical trial participation for minoritized populations are: "having to arrange childcare" with 72% agreement, "experiencing side effects of treatment" with 63%, and "disrupting one's normal routine" with 65%.
Conclusion: The collected data provides a detailed insight as to what each racial group and educational groups consider to be the three most prominent advantages and disadvantages of participating in medical research. Tailored outreach by addressing the disadvantages and advantages of participation is necessary for minority populations to build trust within medical research. Progression in clinical trial studies recruitment is vital to accurately reflect the diverse population of the U.S. Researchers could use the data to develop and apply these principles to potentially increase minority population participation in clinical trials and lessen the gap. Without this representation, the health disparities gap will continue to widen as minority groups are not considered potentially leading to increased adverse effects in the generation of new therapies.
Mentors: Many thanks to our mentor Dr. Lauren Gilbert for her support and encouragement in our project work, the committed University of Houston College of Medicine, Humana Integrated Systems Sciences Institute Faculty and Staff including, Dr. Woodard, Dr. Adepoju, Dr. Beech, Dispensary of Hope, and the Community Research Advisory Board (CRAB)
Suppression of Host Humoral Immunity by Borrelia burgdorferi Varies Over the Course of Infection
No full textLyme disease is the most common vector-borne illness in the U.S. with approximately 476,000 cases each year. Borrelia burgdorferi, the spirochetal agent of Lyme disease, utilizes a variety of strategies to evade and suppress the host immune response, which enables it to chronically persist in the host. These strategies include complement inhibition, antigenic variation, and suppression of adaptive immunity. The resulting immune response is characterized by unusually strong IgM production and a lack of long-term protective immunity. Previous studies in mice have shown that infection with B. burgdorferi also broadly suppresses host antibody responses against unrelated antigens. Here we aimed to assess how the host’s ability to produce antibodies against an unrelated antigen may change over the course of infection with B. burgdorferi and whether, if at all, the immune system returns to baseline following antibiotic treatment. Mice infected with B. burgdorferi and concomitantly immunized with recombinant SARS-CoV-2 spike protein had an abrogated antibody response to the immunization. To further define how long this humoral immune suppression lasts, mice were immunized at 2-, 4-, and 6-weeks post-infection. Suppression of host antibody production against the SARS-CoV-2 spike protein peaked at 2 weeks post-infection but continued for all timepoints measured. Antibody responses against the SARS-CoV-2 spike protein were also assessed following antibiotic treatment to determine whether this immune suppression persists or resolves following clearance of B. burgdorferi. Host antibody production against the SARS-CoV-2 spike protein returned to baseline following antibiotic treatment; however, anti-SARS-CoV-2 IgM remained high, comparable to levels found in B. burgdorferi-infected but untreated mice. Thus, our data demonstrate restored IgG responses following antibiotic treatment but persistently elevated IgM levels, indicating lingering effects of B. burgdorferi infection on the immune system following treatment.State of Texa
Pregnancy-induced oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function
Get PDFPregnancy is associated with neural and behavioral plasticity, systemic inflammation, and oxidative stress, yet the impact of inflammation and oxidative stress on maternal neural and behavioral plasticity during pregnancy is unclear. We hypothesized that healthy pregnancy transiently reduces learning and memory and these deficits are associated with pregnancy-induced elevations in inflammation and oxidative stress. Cognitive performance was tested with novel object recognition (recollective memory), Morris water maze (spatial memory), and open field (anxiety-like) behavior tasks in female Sprague-Dawley rats of varying reproductive states [nonpregnant (nulliparous), pregnant (near term), and 1-2 mo after pregnancy (primiparous); n = 7 or 8/group]. Plasma and CA1 proinflammatory cytokines were measured with a MILLIPLEX magnetic bead assay. Plasma oxidative stress was measured via advanced oxidation protein products (AOPP) assay. CA1 markers of oxidative stress, neuronal activity, and apoptosis were quantified via Western blot analysis. Our results demonstrate that CA1 oxidative stress-associated markers were elevated in pregnant compared with nulliparous rats (P </= 0.017) but there were equivalent levels in pregnant and primiparous rats. In contrast, reproductive state did not impact CA1 inflammatory cytokines, neuronal activity, or apoptosis. Likewise, there was no effect of reproductive state on recollective or spatial memory. Even so, spatial learning was impaired (P </= 0.007) whereas anxiety-like behavior (P </= 0.034) was reduced in primiparous rats. Overall, our data suggest that maternal hippocampal CA1 is protected from systemic inflammation but vulnerable to peripartum oxidative stress. Peripartum oxidative stress elevations, such as in pregnancy complications, may contribute to peripartum neural and behavioral plasticity.NEW & NOTEWORTHY Healthy pregnancy is associated with elevated maternal systemic and brain oxidative stress. During postpregnancy, brain oxidative stress remains elevated whereas systemic oxidative stress is resolved. This sustained maternal brain oxidative stress is associated with learning impairments and decreased anxiety-like behavior during the postpregnancy period.This study was supported by National Institutes of HealthGrants R01 HL146562-04S1 (to S.G.) and T32 AG020494 (to S.M.)and American Heart Association Grants 22POST-903250 (toJ.L.B.), 22PRE-900431 (to J.J.G.), and 23PRE-1012811 (to S.M.T)
Current Treatment Options for Patients with Inherited Retinal Dystrophies and Ongoing Gene Therapy Clinical Trials
Get PDFInherited retinal dystrophies affect a great majority of the population, causing millions of people to suffer from these diseases. This systematic review seeks to evaluate current treatment options for patients with leber's congenital amaurosis and retinitis pigmentosa with the biallelic RPE65 mutation. Currently, voretigene neparvovec-rzyl is approved by the US Food & Drug Administration (FDA) for the treatment of RPE65-mediated inherited retinal dystrophies. However, thus far, the gene therapy has been inaccessible for some patients due to the high expense of the treatment. Further research involving clinical trials allows for other options to be investigated leading to an overall better patient experience and accessibility factor. In addition, the world's first gene therapy approved for treatment of RPE65-mediated inherited retinal dystrophies allows researchers to establish more effective treatments that may have better outcomes. This gene therapy also opened the world to the idea of a treatment for inherited retinal dystrophies due to the limited amount of research in this field
Age-Related Dysfunction in Balance: A Comprehensive Review of Causes, Consequences, and Interventions
Get PDFThis review delves into the multifaceted aspects of age-related balance changes, highlighting their prevalence, underlying causes, and the impact they have on the elderly population. Central to this discussion is the exploration of various physiological changes that occur with aging, such as alterations in the vestibular, visual, proprioceptive systems, and musculoskeletal degeneration. We examine the role of neurological disorders, cognitive decline, and medication side effects in exacerbating balance issues. The review underscores the significance of early detection and effective intervention strategies in mitigating the risks associated with balance problems, such as falls and reduced mobility. It discusses the effectiveness of diverse intervention strategies, including exercise programs, rehabilitation techniques, and technological advancements like virtual reality, wearable devices, and telemedicine. Additionally, the review stresses the importance of a holistic approach in managing balance disorders, encompassing medication review, addressing comorbidities, and environmental modifications. The paper also presents future research directions, emphasizing the need for a deeper understanding of the complex mechanisms underlying balance changes with aging and the potential of emerging technologies and interdisciplinary approaches in enhancing assessment and intervention methods. This comprehensive review aims to provide valuable insights for healthcare providers, researchers, and policymakers in developing targeted strategies to improve the quality of life and ensure the well-being of the aging population.This work was supported by National Natural Science Foundation of China, No. 82172529 (to JW), No. 82202785 (to YL) and the Scientific Research and Innovation Program of Shanghai Education Commission, No. 2019-01-07-00-02-E00064 (to G-YY)
Fostering Well-Being: The Journey of Developing a Microcredential for Instructional Designers
Get PDFThis presentation documents the evolution of the Division of Academic Innovation (DAI) Thriving Hub into a structured microcredential program designed to promote professional growth and well-being among instructional design professionals at UNTHSC. Featuring two distinct pathways—"Emerging Topics in Educational Technology" and "Social Wellbeing in the Workplace"—the initiative emphasizes peer-led learning, active participation, and reflective practice. Through a phased implementation plan, the program aligns team development with institutional goals for continuous improvement and innovation. The presentation articulates the competencies, milestones, and evaluative components necessary for credentialing, offering a replicable model for enhancing workplace engagement through microcredentialing in higher education