2023

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Accessory Muscle from the Trapezius Muscle into the Thoracolumbar Fascia
(2023) Kara, Ramiz; Tran, Lianna; Vasilev, Viktor; Luu, Dustin
Background: As part of the superficial back musculature, the trapezius and latissimus dorsi muscles play an integral role in upper body mobility. The trapezius functions in neck extension and movement of the scapula, allowing motions such as elevation, depression, upward rotation, and retraction. The latissimus dorsi functions to internally rotate, adduct, and extend the arm. Anatomical variations of these muscles have been previously reported in literature and are associated with aplasia, hypoplasia, agenesis, and variations in vasculature and innervation. Case Information: We present our discovery of a unique trapezius muscle variant that was discovered upon standard cadaveric dissection. The variant is approximately 6.0 cm in length. The accessory muscle is observed to originate from the inferolateral fibers of the trapezius and inserts into the superomedial fibers of the latissimus dorsi muscle. The inferior aspect of the muscle-tendon runs continuously with the latissimus dorsi muscle tendon, ultimately inserting into the thoracolumbar fascia. The superior aspect of the muscle belly narrows to fuse with the deep surface of the trapezius muscle. The middle portion of the accessory muscle was surrounded by its own fascial sheath, separating it from both the superficial cutaneous tissue and the deep musculature. Conclusion: Anatomical variants arise commonly in individuals, and their clinical significance - especially in the routinely used upper body muscles - can either impair quality of life or be asymptomatic. More specifically, accessory muscle variants, like the one we found, are important to note due to their use in surgical procedures, relevance during diagnostic imaging, and their potential for clinical manifestations (such as pain syndromes and scoliosis). We suggest that accessory muscle variants could offer alternative options to surgeons when considering tendon transfer procedures. Next, we propose that the presence of a unilateral accessory muscle could play a role in scoliosis. The trapezius and paraspinal muscles, and their connections with the spinal vertebrae, contribute to the balance of forces that, when imbalanced, may present as idiopathic scoliosis. Previous studies have shown that abnormalities in the paraspinal muscles, like the trapezius, have a strong correlation with idiopathic scoliosis. Lastly, we suggest the presence of unilateral accessory muscles may give rise to pain symptoms.
Active suppression of adaptive immunity by Borrelia burgdorferi in the murine host
(2023) Williams, Megan; Zhang, Yan; Kilgore, Rebecca; Allen, Michael
Purpose: Borrelia burgdorferi(Bb), the spirochetal agent of Lyme disease, utilizes a variety of tactics to evade and suppress the host immune response which enable it to persist chronically. These tactics can include complement inhibition, antigenic variation, extracellular matrix degradation, and adaptive immune suppression. Adaptive immune suppression by Bb is still not well understood. Previous studies have shown that lymph node (LN) germinal centers generated in response to Bb collapse one-month post-infection. The resulting humoral immune response is characterized by unusually strong and persistent IgM production and lack of long-lived immunity. Here we aimed to better characterize how Bb manipulates the host humoral immune response, ultimately resulting in failure to clear the infection. Methods: Mice were infected with Bb and concomitantly immunized with recombinant SARS-CoV-2 spike protein to measure the antibody response to the immunization and how it may be dampened by infection with Bb. We also immunized mice at 2-, 4-, and 6-weeks post-infection to test how long this humoral immune suppression lasts. Using RT-qPCR, we also examined changes to gene expression in murine LNs 15 days post-infection to better characterize what may be causing this observed immune dysfunction. Results: Suppression of host antibody production against the rSARS-CoV-2 spike protein peaked at 2 weeks post-infection but continued for all timepoints measured. We also found that live Bb, but not heat-killed (HK) Bb, broadly suppressed many genes related to T cell homing and function. Genes which play a critical role in the establishment and maintenance of T cell zones within the LNs, Ccl19 and Ccr7, were significantly downregulated. This was interesting considering previous studies have provided evidence of disorganization of LN architecture and the disruption of T cell zones beginning around 10 days post-infection. In addition, both Il2 and Il2ra were significantly downregulated, which is typically observed during the resolution of infection and indicates a lack of antigenic restimulation. Conclusion: These data suggest potential T cell disruption by Bb, which may play a role in the failure to mount an appropriate humoral immune response to the infection.
Acute sex difference in response to repeated mild traumatic brain injury in mice
(2023) Kuo, Aaron; Schreihofer, Derek; Sumien, Nathalie; Vann, Philip; Ahmed, Affan
Acute sex difference in response to repeated mild traumatic brain injury in mice Aaron Kuo, Philip Vann, Nathalie Sumien, Ahmed Affan, Derek Schreihofer Background: Repetitive mild traumatic brain injury (rmTBI), such as that occurring in contact sports, is associated with the development of neurodegenerative diseases of aging. Severe TBI and repetitive concussions are associated with chronic traumatic encephalopathy (CTE), Alzheimer’s disease (AD), and Parkinson’s disease (PD), among others. However, less severe injuries may also lead to delayed neurological disfunction if repeated often and without sufficient rest time between injuries. Previously, we found that the progression of behavioral deficits in males and female mice differed from 5 to 15 weeks after 25 rmTBI. Both sexes showed motor deficits at 5 weeks, but only males showed affective and cognitive deficits at 15 weeks. Purpose: This study tested the hypothesis that rmTBI neurological deficits in male mice will appear earlier after rmTBI than in female mice. Methods: C57BL/6 male and female mice (8 wk old) were assigned to sham and rmTBI groups (n=20/group). Lightly anesthetized mice received 7 mild head injuries, once a day (M-F) using a weight drop model (75 g from 1 meter) that included a free fall with rotational injury. Five minutes after the final injury, mice were tested on a balance beam. Additional behavioral assessments began the following day. Results: No sex differences in balance beam performance were observed 5 minutes after the final injury. There were no significant effects of rmTBI on vestibular motor function assessed with a rotarod; cognition assessed with the Morris water maze; or affective behavior assessed with the elevated plus maze. However, in the open field test there was a significant increase in total distance traveled in rmTBI mice (F1,35 = 6.47, P=0.016). Post-hoc analysis revealed that this effect was only significant in male mice (Fisher LSD, P<0.05), supporting the hypothesis that males exhibit earlier deficits than females. Conclusion: At extended time points following rmTBI, both male and female mice develop motor deficits. However, up to 15 weeks after injury, only male mice experience cognitive and affective deficits. The current study reveals that male mice also display hyperactivity in the week after rmTBI that is not observed in female mice. Thus, sex differences in response to rmTBI are apparent both in the acute and chronic phase of injury and suggest that interventions to reduce brain injury may require different timing for males and females. Ongoing studies are examining potential differences in biochemical and histological responses in the brains of male and female mice. AUP: 2021-0035
Addressing Age-Appropriate Cancer Care for Adolescents and Young Adults
(2023) Tran, Kylie; Elledge, Daniel; Hoeft, Alice; Albritton, Karen
Purpose: Adolescents and young adults (AYAs), normally defined as patients between 15 and 39 years of age, are often lost in the healthcare system that concentrates primarily on pediatric and adult cancers1. AYA cancer presentation can differ and treatments are less established compared to pediatric and adult cancers2. Many AYA patients are treated in pediatric facilities, which can lead to age-appropriate needs not being met. The goal of this project is to examine the AYA patient experience and assess if AYAs receive age-appropriate care at Cook Children’s Hospital in Fort Worth, Texas. Methods: Patient reported outcomes surveys were administered to AYA patients diagnosed between 1/1/2016 and 1/1/2020 with at least one of the following cancers: acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, testicular germ cell tumor, ovarian germ cell tumor, or sarcoma. Eighty-five patients were eligible to participate in the study. The survey and chart review included information pertaining to demographics, socioeconomic factors, treatment, and diagnosis-related questions. Results: Seventeen patients have completed the survey. Patients rated age-appropriateness and quality of care on a five-point Likert scale. On average, patients rated the following aspects of their care as highly satisfactory for age-appropriateness: communication with medical staff (M = 4.80, SD = 0.40), staff recognition of life events (M = 4.71, SD = 0.46), provider attitude (M = 4.86, SD = 0.37), and support provided to their families (M = 4.82, SD = 0.40). Although still highly rated, the physical environment (M= 4.38, SD = 0.91) and recreational activities (M= 4.35, SD = 0.87) were reported to be slightly lower than the other categories for age-appropriateness. Conclusions: AYA patients face unique challenges related to their cancer presentation and psychosocial needs. Interactions between patients, their physicians, and their environment all contribute to the patients' treatment experience and providing comprehensive, age-appropriate care is important. Overall, patients reported receiving age-appropriate care at Cook Children’s Hospital but reported slightly less satisfaction with the facilities and age-related activities. Based on these findings, continuing to establish age-appropriate resources and physical spaces for AYA patients can greatly enhance their quality of care and treatment experience. Beginning in 2016, Cook Children’s AYA clinic had already initiated changes to establish more supportive resources for AYAs, including creating and renovating a designated AYA lounge and implementing more programmatic psychosocial care through psychological interventions and AYA-specific support groups. References 1. Alvarez, The Lancet Oncology, 2022 2. Smith, Pediatric Blood & Cancer, 2019
Adult-Onset Still’s Disease Masquerading as Candida Sepsis
(2023) Lee, Jessica; Khoncarly, Bilal; Patel, Riddhi; Koldstad, Rebecca; Khan, Ammad; Van, Nga; Upadhyay, Bishwas
Background: Adult Onset Still’s Disease (AOSD) is a rare systemic inflammatory disorder characterized by daily fever, polyarthritis, and transient salmon-pink rash typically at the peak of fever. It is hypothesized to be a reactive syndrome triggered by an infectious process. However, the etiology is still unknown. The Yamaguchi diagnostic criteria is commonly used to classify AOSD. Although there is not a specific laboratory or imaging study used to diagnose AOSD, a serum ferritin > 1000 ng/mL is typically seen. Case presentation: Here we present a case about a 66 year old male with a past medical history of hypertension, hyperlipidemia, uncontrolled type II diabetes mellitus (DMT2), atrial fibrillation, hypothyroidism, chronic knee pain, and tobacco abuse who presented to the hospital with subjective fevers, myalgias, and generalized weakness for 2 weeks. The patient also had a pruritic, erythematous rash in the bilateral lower abdominal region which extended to the inguinal folds over the last 15 days. Physical exam revealed oral thrush covering his tongue. The patient also had chronic, bilateral knee swelling, erythema, and warmth without formal diagnosis of arthritis in the past. The patient was febrile, tachycardic, and hypotensive on admission. Complete blood count was remarkable for leukocytosis with a white blood cell count of 12.35 K/mm3. Based on his initial presentation, the patient was diagnosed with sepsis secondary to candida infection. The patient’s history of DMT2, Jardiance use, and tobacco abuse further elevated suspicion of candidiasis. However, his fever was non-responsive to antifungals, antibiotics, or antivirals. Given his bilateral knee, elbow, and wrist swelling, we investigated possible rheumatologic processes. Further workup revealed an elevated erythrocyte sedimentation rate (ESR) of 106 mm/Hr, elevated C-reactive protein (CRP) of 353 mg/L, and elevated ferritin of 29125 ng/mL suggestive of severe inflammation. The patient’s daughter later revealed he had an erythematous rash most notable at the height of his fever. The Yamaguchi criteria were used to diagnose AOSD. Patient presentation was positive for four major criteria and two minor criteria. His elevated ferritin > 1000 ng/mL solidified the diagnosis. His fever ultimately improved after corticosteroid treatment. Discussion: Diagnosis of AOSD still remains a challenge because it is a diagnosis of exclusion. Although the Yamaguchi criteria are the most sensitive criteria for identifying AOSD, cases do not always present classically. Sepsis is an exclusion criteria for AOSD. The patient’s initial presentation was highly suggestive of sepsis, which initially delayed identification of AOSD. Also the salmon-pink rash that is classically presented with AOSD masqueraded as candida infection in addition to his oral thrush. This case illustrates the diagnostic challenges of AOSD. Delay in diagnosis remains a problem with AOSD, because delay can lead to increased risk of complications including disseminated intravascular coagulopathy (DIC), thrombotic thrombocytopenic purpura (TTP), macrophage activation syndrome, pulmonary hypertension, and diffuse alveolar hemorrhage. Further investigation is critical for understanding the etiology of AOSD as well as diagnostic protocols to expedite management and prevent life-threatening complications.
Aggressive Fibromatosis of the Quadratus Lumborum in A 28-Year-Old-Female: A Case Report
(2023) Gattu, Tejashwini; Ngo, Wayne; Martinez, Maria; Schultz, Steven
Background: Desmoid tumors (aggressive fibromatosis/desmoid-like tumors) are rare neoplasms that consist of proliferations of clonal fibroblastic proliferation that are aggressive and locally invasive. While the exact cause of desmoid tumors is unknown, they are associated with hereditary conditions such as Gardner’s syndrome and familial adenomatous polyposis both of which arise due to inactivating mutations of the APC gene. On the other hand, fibromatosis that arise sporadically generally has an activating mutation of the CTNNB1 gene which encodes beta-catenin. A history of trauma such as injuries and previous surgeries has also been associated with the development of desmoid tumors. Desmoid tumors are rare with an estimated incidence of 2-4 per million people per year and make up 0.03% of all neoplasms. Early diagnosis and treatment of desmoid tumors are crucial in minimizing morbidity and mortality. Fibromatosis primarily arise in the extra-abdominal setting which comprises approximately 58% of all cases. Among this, most arise in the shoulder or pelvic girdle region. Here, we report an uncommon site of origin for desmoid tumors. Case Presentation: A 28-year-old female with no previous history of trauma presented with lower back pain with radiculopathy radiating to her right hip. An MRI of the lumbar spine revealed a mass in the right iliac fossa and an abdominal and pelvic MRI showed a large circumscribed posterolateral right intra-abdominal wall mass extending up from the right iliac fossa with low signal bands on T1W and T2W imaging. There were intermediate signal areas elsewhere with islands of enhancement. Subsequent abdominal and pelvis CT showed a right posterior pelvic mass measuring 19x13x10 cm concerning for a neoplasm with fibrotic components. The mass originated from the right quadratus lumborum muscle. It involved the posterior distal transversus abdominis and internal oblique abdominal muscle anteriorly. Distally, it involved the iliacus muscle. Differential diagnoses were abdominal wall aggressive fibromatosis/desmoid tumor, solitary fibroid tumor, sarcoma, unusual GIST tumor, neuroectodermal tumor versus nerve sheath tumor, metastasis, lymphoma. A biopsy was performed and results were consistent with aggressive fibromatosis. Conclusion: Desmoid tumors are rare tumors with a locally aggressive and variable course and high risk of local recurrence. The diagnostic workup often includes imaging with MRI and CT and which allows for determining the origin and involvement of adjacent structures to guide possible interventions. Diagnosis can only be confirmed through biopsy which will reveal a monoclonal proliferation of fibroblasts. Treatment ranges from observation, radiotherapy, surgery, and various medications. Because this case presents a desmoid tumor originating from an uncommon site of origin in the quadratus lumborum region, we hope to provide a better clinical picture for the screening and diagnosis of similar aggressive fibromatosis.
Analysis of Key Cellular Changes of Triple Negative Breast Cancer Cells in Response to Kinase-Inhibiting BI2536 and Associated Derivatives
(2023) Baker, Christopher; Rinderle, Caroline; Bunnell, Bruce
Purpose: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer that grows quickly and has higher rates of metastasis and reoccurrence relative to other Breast Cancer subtypes that make it, in general, a much more dangerous subtype of breast cancer. The Kinase Chemogenomic Set (KCGS) is a collection of 187 kinase-inhibiting compounds with broad activity across 215 different kinases. We hypothesize that this plate contains compounds with the potential to inhibit TNBC and that exploring the transcriptomic and proteomic changes in TNBC cells may give insights into novel treatment targets. Methods: To test this hypothesis, we have utilized two main cell lines, the MDA-MB-231 line and a patient-derived xenograft line, the TuX-BxC-4IC cell line. Measurements have been taken at various time points up until 72 hours at various concentrations of a compound of interest, BI2536, between 1nM and 1uM. Primarily, data will be collected using qRT-PCR to gain insight into the transcriptomic changes during the potential EMT changes. Additionally, various other experiments related to migration, staining, and other essential markers will be conducted on the compound of interest and derivatives of the compound. Results: Initial results and prior work indicate that the compound of interest has moderate success in slowing cancer cell growth. Additionally, initial findings indicate that the compound may succeed in halting and potentially even reversing the EMT process. Conclusion: With this primary data set, we believe that the kinases targeted by the compound may hold potential key targets for the treatment of TNBC.
An Analysis of Student Satisfaction with Active Learning Techniques in an Online Graduate Anatomy Course: Consideration of Demographics and Previous Course Enrollment
(2023) Bradley, Libby; Meyer, Kim; Robertson, Taylor; Kerr, Marcel; Maddux, Scott D.; Heck, Amber; Reeves, Rustin; Handler, Emma
Purpose: Online learning has become an essential part of mainstream higher education, allowing greater access for students. With the increase in online course enrollment, specifically that of anatomy, understanding online teaching best practices is critical. Active learning has previously shown many benefits in face-to-face anatomy courses, including increases in student satisfaction. Currently, no research has measured the satisfaction of several active learning techniques implemented in an asynchronous, online graduate anatomy course. Methods: This study compared the student satisfaction achieved by four active learning techniques with consideration of demographics and previous course enrollment. Survey questions consisted of multiple-choice and Likert-style that asked students to indicate their level of satisfaction with the active learning techniques. One hundred seventy (170) students completed the online anatomy course and surveys. Results: Students were more satisfied with question constructing and jigsaw than with concept mapping and team-learning module. Additionally, historically excluded student groups (underrepresented racial minorities) were more satisfied with active learning than White students. Age, gender, previous anatomy experience and/or online course experience did not influence the satisfaction of the active learning techniques. However, students with higher GPAs and those who had no graduate degree were more satisfied with the active learning techniques than students who had lower GPAs and those with a graduate degree. Conclusion: These findings provide evidence that students enrolled in an online graduate anatomy course were satisfied with the active learning techniques, dependent on the specific technique, demographics, and previous course enrollment. Results provide anatomy educators with a better understanding of which techniques work best in an online anatomy course. Currently, there is a lack of research comparing active learning techniques in an online learning environment. These findings provide online anatomy educators with evidence that active learning techniques improve satisfaction, with consideration of student demographics and previous course enrollment.
Analysis of survivin expression in black and white breast cancer patient tissue
(2023) Brown, Kerrie; Fang, Yisheng V.; Sankpal, Umesh T.
Purpose: Survivin is a protein that belongs to the inhibitor of apoptosis family. It inhibits the activation of caspases and is also involved in the regulation of the cell cycle. Survivin is normally expressed during development with no expression detected in most adult differentiated tissues. However, high expression of this protein is found in many cancers which correlates with poor prognosis. Breast cancer disproportionately affects black women who have significantly higher mortality rates compared to white women with breast cancer. We hypothesize that higher expression of Survivin in Black cancer patients correlates with their higher mortality rates. In this project, we compared the level of expression of survivin in breast tumor tissue from Black and White cancer patients. This was done using immunohistochemical (IHC) staining technique of tumor tissue sections and analysis of The Cancer Genome Atlas database. Detecting differential expression of Survivin between the two racial groups and within different subtypes of breast cancer could lead to the development of Survivin as a diagnostic and/or prognostic marker as well as a possible therapeutic target. Methods: Our first approach was to analyze the TCGA database to confirm our hypothesis that there is differential expression of survivin between the two racial groups and within different subtypes of breast cancer. This involved RNA-seq data analysis using various tools available online. Secondly, breast tumor tissue, representing different subtypes of breast cancer, from Black and White patients, was analyzed by immunohistochemistry (IHC) using survivin specific antibodies. The protocol for nuclear and cytoplasmic Survivin detection was standardized. The IHC data, in the form of percent staining (nuclear and cytoplasmic), was then analyzed by semi-quantitative methods using H-score and Allred scores. Results and Conclusions: Results from the analysis of TCGA database and our IHC data indicate significantly higher expression of survivin in tumors from Black patients compared to White. Differential expression was also observed between different subgroups of breast cancer, with high expression in the most aggressive triple negative (TNBC) form of breast cancer. Coincidently, the occurrence of TNBC is higher in Black women compared to White women. We also observed higher nuclear expression in Black patients compared to White patients, which has been associated with poor outcomes. Based on the vast literature suggesting that survivin plays a key role in cancer progression, we believe that survivin could be a useful diagnostic and/or prognostic marker or a therapeutic target to combat the racial disparity in breast cancer.
Analyzing the Effectiveness of Wellness Resources Provided for Medical School Students
(2023) Rama, Kush; Patel, Pooja; Adhikari, Pratichha; Ziller, Rynn
Background: There exists well-documented evidence demonstrating that physicians and medical school students practicing preventative lifestyles are more likely to promote prevention to their patients, which is especially important given the escalation of chronic conditions in the United States. The arduous nature of medical school challenges the student’s ability to initiate or sustain healthy lifestyle habits even with the various resources available. Several interventions have been created to address medical student wellness; however, there remains a discrepancy in the literature regarding the effectiveness of these resources long-term. Student burnout, which is defined as emotional exhaustion, is still a prevalent issue in the medical profession. Medical schools must emphasize the importance of program evaluations to address the issues that contribute to poor medical student wellbeing. Goal:To create a simple and inexpensive survey that can track the effectiveness of wellness resources that medical students use over the long-term. Methods: A survey that could be implemented at a single point in time or a yearly fashion was developed. The survey was created to collect information on wellbeing markers, resources used, and basic demographic information. The wellness questionnaires used were the WHO-5 Wellbeing Index, Modified Maslach Burnout Inventory (M-MBI), International Physical Activity Questionnaire Short Form (IPAQ-SF), Single Item Sleepy Quality Scale (SQS), and the nutritional questionnaire section from the American Association of Family Medicine’s (AAFP) Lifestyle Assessment Form. The effectiveness of the wellness resources will be assessed in three ways. First, a question will be asked regarding the user’s opinion about the value of the resource to their wellness. Second, the students with poor wellbeing will be identified, and the prevalence of usage of that resource will be documented. Third, the wellbeing markers will be compared to students who use the resource versus students who do not use the resource. Propensity score matching will be used to reduce the confounding variables associated with demographic information and academic factors (average grades, amount of time spent studying in a day, etc.). The data will be collected through Qualtrics and analyzed using IBM SPSS Version 29.0. The first round of the survey will be distributed to first- and second-year medical students between the dates of February 1st -15th. Subjects will be recruited through verbal announcements at the end of mandatory lectures. Discussion and Future Implications: Due to the numerous wellness programs at medical schools, it can be difficult to assess their efficacy because of the time and resources needed. The survey design is built to help medical schools track the performance of their wellness resources in a quick and affordable manner. The data from this survey can help guide decisions about how medical schools can improve the quality of their wellness resources. It is important for medical schools to continue to evaluate their wellness initiatives over the long-term so that they can adapt to the evolving needs of their students.
Animal model of kidney disease induced by high folic acid
(2023) Aldeeb, Sara; Yan, Liang-Jun
Purpose: The kidney is a vital organ that helps the body eliminate waste and toxic substances and return nutrients and vital substances back into the bloodstream. Kidney disease can be categorized into acute kidney injury (AKI) or chronic kidney disease (CKD). This may be caused by numerous risk factors such as ischemia, sepsis, drug toxicity and drug overdose, exposure to heavy metals, and diabetes. However, the exact prognosis from an AKI to CKD is not fully understood. In addition, approximately 37 million individuals in the United States population currently suffer from CKD. Despite the high prevalence of CKD, information is lacking on our understanding of the pathogenesis of AKI and CKD and there are still no available therapeutics that can be used to combat kidney disease effectively. This highlights an urgent need to further study the pathological mechanisms underlying AKI, CKD, and AKI progression to CKD. In this regard, animal models of kidney disease are imperative. Methods: This presentation reviews a widely used animal model of kidney disease, which is induced in mice with folic acid (FA). While a low dose of FA is nutritionally favorable, a high dose of FA is toxic to the kidneys. A high dose of FA is injected intra-peritoneally in the mice. Following a brief description of the procedure for disease induction by FA, major mechanisms of FA-induced kidney injury are then reviewed. This includes observing oxidative stress levels, mitochondrial abnormalities such as impaired bioenergetics and mitophagy, ferroptosis, pyroptosis, and increased expression of fibroblast growth factor 23 (FGF23). This is completed to explore possible pathological mechanisms of kidney disease and thereby the efficacy of a variety of therapeutic approaches may be evaluated. These procedural methods required Institutional Animal Care and Use Committee (IACUC) clearance and proper laboratory training to ensure ethical laboratory practices. The presentation will also highlight an overview of how to obtain IACUC clearance and ethical practice certification. Results: This animal model of inducing high doses of FA can induce both AKI and CKD in mice and therefore can be used to further study AKI to CKD progression. Conclusion: Given that the animal model is reproducible and can recapitulate human kidney disease phenotypes, it should be useful for both studying the pathological mechanisms of kidney disease and identifying effective therapeutic targets to fight kidney disease. This presentation is supported by PDRT at UNTHSC
Annexin A2 in tumor-derived extracellular vesicles: Molecular contributions in metastatic triple negative breast cancer
(2023) Trivedi, Rucha; Vishwanatha, Jamboor
Purpose Tumor-derived extracellular vesicles (TEV) are highly implicated in tissue-specific metastasis. Additionally, TEV interacts with the distant microenvironment to shape a pre-metastatic niche (PMN) for homing the tumor cells. Annexin A2 (AnxA2) is a plasma and endosomal membrane-associated protein. Its high levels have been correlated with poor distant metastasis-free survival and poor overall survival in triple negative breast cancer (TNBC) patients. It is also abundantly present in TEV and recruits TEV-associated cargo such as proteins and microRNAs. Our lab reported that in vivo education with AnxA2 depleted EV led to reduced TNBC metastasis to lungs and brain suggesting a key role in the formation of a PMN. While the presence of AnxA2 in EV has been reported, its contribution in the formation & development of PMN via EV is still unexplored. We aim to evaluate the implications of AnxA2 in EV & elucidate the mechanisms promoting TNBC metastasis. Methods We used shRNA- mediated gene silencing to stably downregulate AnxA2 in organotropic TNBC cell lines derived from the parent MDA MB 231 cells. Differential ultracentrifugation was used to isolate EV from cell culture supernatant & size analysis was done using NTA. Biological characterization was done in concordance with MISEV 2018 guidelines using immunoblotting. Additionally, the EVs will be subjected to quantitative proteomic and transcriptomic analysis to identify differentially expressed proteins and genes upon loss of AnxA2. Results Upon depletion of AnxA2 protein, we observed a significant effect of AnxA2 depletion on its physiological role in plasmin generation. We observed a size distribution of the isolated EV between 30-300 nm. Using immunoblotting we confirmed reduced levels of AnxA2 in EVs derived from AnxA2 depleted TNBC cells. We verified their purity using EV enriched markers - ESCRT, Heat shock proteins & tetraspanins such as CD81, CD9, CD63 & confirmed the absence of negative markers - GM130, calnexin & cytochrome c. Interestingly, we observed a reduced yield of EV with AnxA2 depletion indicating a potential effect on EV biogenesis & release. Conclusion The role of AnxA2 in TEV biogenesis, release and selective cargo loading will lead to potential identification and understanding of the novel secretory and EV protein that may act as a functional regulator in promoting advanced metastasis in TNBC.
Anti-proliferative effects of a copper(II) complex with a thiosemicarbazone ligand against selected human cancer cells
(2023) Fiadjoe, Hope; Lambring, Christoffer B.; Sankpal, Umesh; Alajroush, Duaa; Smith, Chloe; Anderson, Brittney; Mann, Novia; Beebe, Stephen; Holder, Alvin; Basha, Riyaz
Purpose: The frequent relapse and drug resistance associated with the current cancer chemotherapy treatments necessitate the development of alternative strategies. Thiosemicarbazones are a class of metal chelators that have been explored to treat diverse human diseases, including cancer. Copper, a crucial structural component for many significant enzymes and a key catalytic co-factor in redox processes, is being explored for several medical applications. Additionally, the anti-cancer activity of certain chemotherapeutic agents can be enhanced by the use of copper-containing complexes. This study aimed to evaluate the antiproliferative effects of a copper(II) complex with a thiosemicarbazone ligand (Cu-acetylethTSC or [Cu(acetylethTSC)Cl]Cl·0.25C2H5OH (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide)) against human cancer cell lines, viz., medulloblastoma (DAOY, D283), glioblastoma (LN-229), Ewing sarcoma (TC205, CHLA10), and acute lymphoblastic leukemia (CCRF-CEM, SUP-B15). Methods: These selected cell lines were cultured using standard protocols. Cell viability was measured using a Cell Titer-Glo kit at 48 h after treatment with various concentrations of Cu-acetylethTSC. Each treatment group and the controls were read in triplicates and the data were plotted as percentage cell viability versus concentration of the complex. Dose-response curves were generated based on the cell viability data obtained, and IC50 values were calculated. Cardiomyocytes (H9C2) were also cultured and used to test cytotoxicity in non-malignant cells. Results: Cell viability was inhibited in a dose-dependent manner in all the selected cancer cell lines whiles that of H9C2 was not significantly affected. Conclusion: This indicates that Cu-acetylethTSC was selective for malignant cells. Further studies are underway to understand the efficacy, protein targets, and underlying mechanisms of the role of Cu- acetylethTSC.
Application of Structural Retinal Biomarkers to Detect Cognitive Impairment in a Primary Care Setting
(2023) Nyalakonda, Ramyashree; Petersen, Melissa; Zhang, Fan; Johnson, Leigh; Tolman, Alex; Gutierrez, Alejandra; O'Bryant, Sid; Mozdbar, Sima
Introduction Alzheimer’s Disease (AD) is the most prevalent form of dementia and a leading cause of death in the elderly. The detection of AD remains poor in primary care despite the advancement of neurodiagnostic procedures. There are no rapid and cost-effective tools available to primary care providers to conduct cognitive examinations to diagnose AD. The goal of this study is to determine the predictive ability of structural retinal biomarkers to identify cognitive impairment in a primary care setting. Methods Participants were recruited from Alzheimer’s Disease in Primary Care (ADPC) study. As part of the ADPC Retinal Biomarker Study (ADPC RBS), visual acuity, an ocular history questionnaire, eye pressure, optical coherence tomography (OCT) imaging and fundus imaging was performed. Exclusion criteria included high intraocular pressure defines as greater than or equal to 30 mmHg in either eye, history of adverse effects with pupillary relation, known hypersensitivity to tropicamide or any ingredient in the formulation, active ocular infection or inflammation, history of angle closure glaucoma, or having undergone ocular surgery within the last 6 months. Cognitive diagnoses were assigned algorithmically and verified at consensus review by an expert in the field of dementia. Results Data were examined on a total of 91 participants (59 cognitively unimpaired, 32 cognitively impaired (26 mild cognitive impairment (MCI), 6 AD)). The top biomarkers for predicting cognitive impairment included the inferior quadrant of the outer retinal layers, all four quadrants of the peripapillary retinal nerve fiber layer (pRNFL), and the inferior quadrant of the macular retinal nerve fiber layer. While all four quadrants of the pRNFL are highly important biomarkers for identifying those with cognitive impairment, the inferior and superior quadrants displayed higher relative importance compared to the temporal and nasal quadrants. Conclusion This study was the first to examine the utility of retinal biomarkers in diagnosis cognitive impairment in a primary care setting with models reflecting how it could be employed as a screening tool in practice. The current data provides strong support for continued investigation into structural retinal biomarkers, particularly the retinal nerve fiber layer, as screening tools for AD. In prior studies, preferential thinning of the inner retinal layers is found in AD compared to healthy controls. This study can help distinguish those with cognitive impairment from those cognitively unimpaired. The availability of such a biomarker could increase access to disease modifying treatments once available.
Area deprivation index and cognitive function: A cross-sectional study of the HABS-HD cohort
(2023) Benton, Abigail; Vintimilla, Raul; Hall, James; Johnson, Leigh; O'Bryant, Sid
Purpose: Dementia is an ever-growing group of disorders worldwide. It is proposed that neighborhood socioeconomic status (NSES) is linked with overall health, and this study will evaluate whether NSES is cross-sectionally associated with cognition in non-Hispanic White, African American, and Mexican American participants of the Health and Aging Brain: Health Disparities Study (HABS-HD). Methods: The HABS-HD is a longitudinal study conducted by the Institute for Translational Research at the University of North Texas Health Science Center. Participants (n=1634) were age 50 years or older, and underwent a clinical interview, neuropsychological exam battery, functional examination, head MRI, amyloid PET scan, and blood draw for clinical and biomarker analysis. NSES was measured using the national area deprivation index (ADI) percentile ranking, which considered the variables of education, employment, income, occupation, and housing. Cognition was assessed by the Mini-Mental State Examination, Trails B Exam, FAS Test, Spanish English Verbal Learning Test, and Digit-Symbol Substitution Test. The cognitive performance in those living in the 20% most disadvantaged neighborhoods was compared to those in the 80% least disadvantaged neighborhoods using multiple linear regression models with age, sex, education, and ethnicity as control variables. Results: Those in the most deprived neighborhood group were statistically significantly (p<0.05) younger, less educated, more likely to be female, and more likely to be Mexican American. The means of MMSE and Trails B test were lower in those living in the more deprived neighborhood group (p<0.05). When looking at the linear model of ADI and cognition, after adjusting for covariates, only Trails B scores were related to the higher deprived neighborhood group (t = -0.62, p <0.0001). Conclusion: Our study revealed that some measures of cognitive impairment were higher in people living in the top 20% disadvantaged neighborhoods. In future studies, specific markers of deprivation should be analyzed along with cognitive impairment to more specifically advocate for beneficial change. Further, due to sex and ethnicity being significant cofounders, analysis should be run by ethnicity to investigate this distinction.
Assessing HSC Health Pediatric Clinic Adherence and Barriers to HealthySteps Screenings
(2023) Rodriguez, Pilar
Purpose: HealthySteps is a program created to provide developmental support to patients aged up to three years old and their families. Children are monitored to make sure they are reaching developmental milestones. Implementation and adherence to the HealthySteps competencies are monitored yearly per clinic. Each clinic can self-assess through a Fidelity Implementation Checklist, where each indicator is graded as either: did not begin, does not meet fidelity, approaching fidelity, meets basic fidelity, or meets optimal fidelity. When the optimal goals of HealthySteps are followed, the program had nationwide significant benefits for the patients, parents, and pediatric care team. Methods: The UNT Health Science Center Pediatric Clinic was analyzed for its implementation and fidelity to HealthySteps developmental and autism screening competencies. Data was collected from Jan. 2017 – July 2022 beginning when HealthySteps was implemented at the clinic and analyzed yearly. The number of patients receiving at least one developmental screening a year and one autism screening by 28 months were calculated from the total number of patients 0 – 3 years of age. Results: Developmental screenings have improved from "Approached Fidelity” to "Meets Basic Fidelity,” while autism screenings have gone from "Approaching Fidelity” to "Does Not Meet Fidelity.” Conclusions: Barriers to patient screenings could include the following: patients coming late to appointments leading to a rushed visit, tablet technology failure, data entry issues from patient check-in to EHR, EMR content access, new staff not being aware of the HealthySteps program and its benefits, and staff forgetting to administer the screenings. To begin reaching for the "Meets Optimal Fidelity” target, the most attainable goal is to establish better communication between the clinic and HealthySteps specialists with more consistent scheduled meetings.
Assessing Incontinence Reporting by Women at a Rural Texas Clinic
(2023) Katz, Hannah; Hadley, Lesca
Abstract Urinary incontinence is estimated to affect between 20-45% of women in the US; a potential reason that estimates vary is due to underreporting of symptoms. In Eagle Lake, Texas, family physicians are the main source of health education concerning uro-gynecologic issues in women. No local Ob-Gyn or urology specialists practice in Eagle Lake. The two most established family physicians in Eagle Lake are male and they recently discontinued obstetric care. The goal of this project was to assess the prevalence of incontinence and reporting of symptoms by female patients in Eagle Lake, in lieu of a local Ob-Gyn or urologist. The goal of this project was to assess the prevalence of incontinence and reporting of symptoms by female patients in an Eagle Lake Family Medicine clinic, where factors exist which might present barriers to reporting. Methods A paper survey was created the Questionnaire for female Urinary Incontinence Diagnosis was used to screen for incontinence in female patients 55 years and older. Questions concerning willingness to discuss symptoms and use of UI medications were asked in multiple-choice format. Data was collected for 10 weeks, and percentages were calculated in Microsoft Excel. Results Out of 51 total participants, 50.9% screened positive for incontinence and 17.86% take bladder control medications. Out of women with incontinence, 60.71% indicated they have not brought up symptoms to a physician. Out of those who have not brought up symptoms, 13.89% indicated they would not see a physician for bladder symptoms, 13.89% indicated they would see a female physician only, and 69.44% indicated they would see either a female or male physician. Out of women with incontinence who have brought up symptoms with a physician, 27.27% reported symptoms to a female physician, 54.54% have reported symptoms to a male physician, and 18.18% reported symptoms to both a male and a female physician. Conclusions This data demonstrates that more than half of female patients 55 years and older at Rice Medical Associates are incontinent, that more than half of the incontinent women have not discussed their symptoms with a physician, and that less than twenty percent of the incontinent women are on medication for it. Some reasons for underreporting may include insufficient screening in clinic, lack of health literacy on when to seek care, and patient avoidance of discussions concerning "delicate” uro-gynecologic matters. The data shows that some women choose only to discuss bladder symptoms with a female physician, while some choose not to discuss their symptoms at all. Additionally, there were two patients who refused to complete the survey because they were uncomfortable with the topic. Due to research bias from sampling patients in a male family practitioner’s clinic, further studies should survey women outside of a healthcare setting and clarify whether reporting would be different at an Ob-Gyn office. This study indicates the need for purposeful screening for incontinence by rural family physicians, to compensate for underreporting of uro-gynecologic issues by women in areas with limited healthcare options.
Assessing Postural Sway Among Older Adult Females with Hypertension
(2023) Bautista, Trissha Belle; Adams, Aminah; Kennedy, Shawn; Camp, Kathlene E.; Patterson, Rita
Purpose: Hypertension and use of antihypertensive medications have been generally suggested as risk factors for falls; however, supporting evidence remains unclear on the link between hypertension and balance. With minimal research assessing postural control using a force plate among older adults with hypertension, the purpose of this study is to evaluate the relationship between postural sway and blood pressure status and identify variables that contribute to falls. Methods: This study is a retrospective, matched case-control analysis incorporating Quiet Stance Test data from the UNTHSC Human Movement Performance Lab for a case group of older adult females aged 55 to 94 with hypertension (n=100) and an age-matched and gender-matched normotensive control group (n=44) generated from previous studies conducted through the UNTHSC HMP Lab. The Quiet Stance Test involved participants standing barefoot with disposable foot covers, on pre-marked footprints on a force plate (Bertec, Columbus, OH and BioSway, Shirley, NY), both arms relaxed on the sides while looking at an eye-level target for three 10-second trials each in eyes open (EO) and eyes closed (EC) conditions. Twenty sway variables were analyzed using Paired Samples t-Test. Data were also stratified for age and height for One-Way ANOVA and Pearson Correlation tests. Tables were generated to compare mean differences between case and control groups in the EO and EC conditions. (UNTHSC IRB# 2013-102) Results: Participants’ ages ranged from 55 to 90 (M=70.7, SD=9.3) and height from 1.45m to 1.78m (M=1.62, SD=0.07) in the case group. In the control group, participants’ ages ranged from 57 to 89 (M=68.8, SD=6.0) and height from 1.47m to 1.73m (M=1.62, SD=0.06). Roughly 80% of all participants identified as White. The Paired Samples t-Test comparing EC and EO conditions revealed significant mean differences (p<.001) for thirteen of twenty sway variables in the case group. Meanwhile, the control group showed no significant mean differences in any variable. The mean differences for four of twenty sway variables were significant (p<.001) for at least one of the height subgroups in the case group (EC condition), while the control group had no significant mean differences. The only variable that was found to have significant (p<.001) mean differences for at least one of the age subgroups is rotational frequency for the case group (EC condition). For the same group and condition, a significant positive correlation was found between rotational frequency and age (r=0.404, p<.001). The center of pressure’s (COP) position is dynamic. Rotational frequency is a measure of COP instability and is the mean velocity of the COP traveling over a circular path defined by the mean displacement from the center position of the COP stabilogram. Conclusion: These findings suggest there may be differences in balance between normotensive and hypertensive older adult females related to age and height. A limitation of this study is that the sampling of convenience included hypertensive subjects that also have back pain concerns. Further studies should include male participants, create more racially diverse research cohorts, and consider comorbidities as variables that may provide insight into other influences on sway.
Assessing the Impact of Senate Bill 8 on Texas Medical Students’ Future Specialty Choice and Intended Location of Practice
(2023) Benavides, Sienna; Katz, Hannah; Davis, Taylor; Papa, Frank
Purpose On June 24, 2022, the Supreme Court overturned their 1973 ruling on Roe v. Wade, spurring Texas to enact "trigger law” 170A, extending the ban on abortion beginning at fertilization. The goal of our research is to evaluate whether Texas medical students’ choices of women’s health related specialties such as OB-Gyn and Family Medicine (FM) and/or intended location of practice have been impacted in response to these legal changes. Although many professional organizations released statements in response to these law changes, the impact this legislature has on medical students has not been summarized. It is important to understand how medical students are influenced by legal changes in healthcare, as the future distribution and availability of physicians is dependent on their choices. Methods An anonymous, Qualtrics survey consisting of six multiple choice and one free response question was dispersed via email list-serves to all current students at the Texas College of Osteopathic Medicine in Fort Worth, Texas. Only responses from students who indicated they have ever been interested in Ob-Gyn and/or FM specialties were included in the final data set. Data was collected for four weeks and then analyzed. Results We received 200 total responses, with 163 qualifying for our final data set. Of the total respondents (n=163), 89.57% answered they intended to practice medicine in Texas prior to the overturning of Roe v. Wade, and 84.05% answered they are currently interested in practicing medicine in Texas. Regarding the decision to pursue Ob-Gyn and/or FM specialties in response to the law change, our survey shows 28.83% of students were deterred, 26.99% were encouraged, and 44.17% were not impacted. Out of those indicating their specialty choice was impacted, 51.65% (n=91) were deterred. Regarding their decision to practice in Texas, our survey shows 45% were deterred by the law changes, 18.75% were encouraged, and 36.25% were not impacted. Out of those indicating their location of choice was impacted, 70.59% (n=102) were deterred from practicing in Texas. The alternative desired locations were Colorado (10), California (17), New York (7), New Jersey (2), Illinois (2), Washington (2) or abroad. Conclusions Our data shows the majority of students’ decisions to pursue Ob-Gyn and/or FM and to practice in Texas were impacted by the overrule of Roe v. Wade, with higher percentages of students being deterred than encouraged for both decisions. Overall, there was a decrease in students who currently want to practice in Texas compared to before the legislative changes. Per answers to our free-response question, one motivation for practicing outside of Texas is wanting to practice somewhere with less limitations on women’s health care and abortion. Alternatively, some students indicated they were encouraged to remain in Texas, as an advocate for reproductive rights. Although there are many variables that influence where one practices medicine, such as family, military commitment, etc., our survey shows that the recent changes in Texas legislation play a strong role in this decision for some students.
Assessing the impact of targeted continuing education training on improving dental hygienists’ HPV-related knowledge
(2023) Farris, Alexandra; Neelamegam, Malinee; Cotter, Jane; Dickinson, Charlene; Johnson, Kaeli; Kline, Nolan; Thompson, Erika; Griner, Stacey
Background Human papillomavirus (HPV) is the most prevalent sexually transmitted infection in the United States and is attributable to various cancers. Approximately 70% of oropharyngeal cancer diagnoses are linked with an HPV infection. HPV vaccination is an effective prevention method that can protect against multiple high-risk strains including those directly associated with oropharyngeal cancer. Given the connection between HPV and oropharyngeal cancer and the frequency of dental visits compared to annual primary care visits, dental hygienists are uniquely positioned to help reduce the risk of HPV infection among their patients through vaccine education and promotion. The goal of this project is to evaluate the impact of a continuing education (CE) training on dental hygienists’ knowledge about HPV and the HPV vaccine. Methods This study used pre- and post-test survey design to collect data from dental hygienists. The CE training was presented at the Southwest Dental Conference on August 26th, 2022, in Dallas, Texas. Prior to the training, all attendees were asked to complete an online survey assessing their knowledge about HPV and the HPV vaccine. Knowledge questions included modes of transmission, types and sites of HPV-related cancers, and vaccine recommendations and indication. For example, "HPV is transmitted through skin-to-skin contact” was asked as a true or false question. With a total of 18 questions on the knowledge scale, participants were awarded 1 point per correct answer and no points for incorrect answers. Higher averages indicated higher knowledge, with 18 being the highest possible score. Following the 45-minute CE, participants completed a second online survey assessing their knowledge. Data were analyzed in SPSS using t-tests to assess for changes from pre-test to post-test. A p-value of <0.05 was considered statistically significant. Results While a total of 453 oral health providers were registered, only practicing dental hygienists (n=112) who had matched pre- and post-surveys were included in this analysis. Out of 18 items, the average number of correct responses pre-CE was 13.7 (SD=2.7), which was significantly higher following the CE (16.8 correct, SD=1.0; p<0.001). The item with the most significant knowledge increase pertained to the type of vaccine available for HPV (a virus-like particle vaccine, 39.1% pre-CE; 92.0% post-CE, p<0.001). Additional items with increases in knowledge included the various types of cancers directly linked to HPV such as anal cancer (54.9% pre-CE; 99.1% post-CE, p<0.001) and penile cancer (50.4% pre-CE; 97.3% post-CE, p<0.001). Conclusions The HPV vaccine is an FDA-approved form of cancer prevention, and the best predictor of HPV vaccination uptake is recommendation from a healthcare provider. The CE training resulted in increased knowledge regarding HPV-related cancers and the HPV vaccine, indicating a need for similar trainings that can help dental hygienists make stronger, more informed vaccination recommendations to their patients. Equipping dental hygienists with the most up-to-date knowledge, effective communication skills, and confidence to promote HPV vaccination among their patients could greatly reduce the number of missed clinical opportunities to recommend and refer for the HPV vaccine.

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