MU-COM Research Day

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MU-COM Research Day is an annual showcase of the the research engagement of the students within the College of Osteopathic Medicine. Content on display are typically poster presentations along with faculty-led discussions of research projects. This event is coordinated by the MU-COM Research Club as well as the Faculty-led Research Club Committee.
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181. Notum: A Novel Regulator of Bone and Its Implications in Osteoporosis

Title Tesim:
Notum: A Novel Regulator of Bone and Its Implications in Osteoporosis
Créateur:
Castanon, Mariah, Hum, Julia, Wacker, Bryan, and Marshall, Vince
Related Url Tesim:
Audio presentation
La description:
Osteoporosis is a silent, dangerous pathology frequently undiagnosed until patients experience a major fracture. About 1 in 2 women and 1 in 4 men ages 50 and above will experience bone fractures due to osteoporosis. Fractures from osteoporosis may lead to a 20% increase in mortality. Notum is a lipase, primarily expressed in the liver, that inhibits the Wnt signaling pathway. The Wnt pathway is involved in growth, development, and healing. Recently, inhibition or absence of Notum led to increased endocortical bone formation and thickness via osteoblast activity in a mouse model. Potentially, modifying factors that affect Notum expression could promote anabolic bone growth.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
Poster
Mot-clé:
osteoporosis, notum, and lipase
date créée:
2020

182. Nusinersin Does Not Mitigate Hip and Spine Pathoanatomy in Spinal Muscular Atrophy Patients

Title Tesim:
Nusinersin Does Not Mitigate Hip and Spine Pathoanatomy in Spinal Muscular Atrophy Patients
Créateur:
Darras, Basil, Miller, Patricia, Snyder, Brian, and Troy, Michael
La description:
Spinal muscular atrophy (SMA) consists of a group of neuromuscular disorders characterized by degeneration of alpha motor neurons, leading to a lower motor neuron-type syndrome. Children afflicted with SMA 1 and 2 are prone to abnormal musculoskeletal growth and deformities affecting axial/appendicular skeleton. Nusinersin is an antisense oligonucleotide therapy administered intrathecally for the duration of the patient’s life with proven benefits of partially maintained muscle strength and respiratory function. The effect of Nusinersin to mitigate developing skeletal deformities, namely the occurrence and progression of scoliosis and hip instability (coxa valgus, acetabular dysplasia) has not been evaluated. We hypothesize SMA patients receiving Nusinersin treatment will have lower incidence/progression of scoliosis and hip instability, less need for surgical correction in proportion to age/motor growth remaining at the time therapy was initiated, compared to similar cohort not treated w/ Nusinersin. 44 subjects with SMA2 were analyzed with a median age at baseline of 4.2 years (range, 1.3-23.9 yrs) and were followed for a median of 7.0 yrs (range, 1.2-14.5 yrs) to a median age of 11.7 yrs (range, 4.1-36.3 yrs). 22 subjects (43%) were treated with Nusinersin for a minimum of 1 year (median 2.2 yrs; range, 1-6.6 yrs). Consecutive radiographs were measured to document the presence/progression of scoliosis and hip instability using Cobb and Migration Index respectively. Established pathoanatomic thresholds for recommending surgical intervention of spine/hip were used to assess failure of Nusinersin. Subjects in Nusinersen group were younger (median, 2.5 vs 6.8 yrs; p=0.001) and had smaller curves at baseline (median, 11° vs 20°; p=0.02). 13/23 subjects untreated with Nusinersen without respiratory assist at baseline, required respiratory assistance at end of follow-up (p<0.001). 9/17 Nusinersen subjects without respiratory assist at baseline, required it at the end of follow-up (p=0.008). No difference in scoliosis progression between pre- vs post-Nusinersen treatment in absolute change (p=0.54) or annual change in Cobb angle (p=0.57). No difference in scoliosis progression between treated vs. untreated SMA patients at any point during follow-up with respect to absolute change (p=0.15) or annual change in Cobb angle (p=0.23). Of 19 patients treated w/ Nusinersen, 15 had serial hip radiographs and of 25 untreated subjects, 11 had serial hip radiographs. All SMA patients had significant hip instability regardless of treatment. Patients with SMA benefit from improved muscle strength in proportion to the neuromotor growth remaining at the time treatment is instituted, treatment with Nusinersin did not ameliorate the skeletal manifestations: scoliosis, parasol rib deformity, hip instability progressed independent of the age that treatment was instituted.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
date créée:
11/22/2019

183. Nutrient Sensing by Tas1R Proteins is Required for Normal Bone Resorption

Title Tesim:
Nutrient Sensing by Tas1R Proteins is Required for Normal Bone Resorption
Créateur:
Shively, Stephen, Davis, Hannah M, Weinstein, Nicholas, Eaton, Michael, Plotkin, Lillian, and Lowery, Jonathan
La description:
Current therapies for low bone mass consist of inhibiting osteoclast activity or increasing the PTH or Wnt signaling pathways. These approaches have significant drawbacks that limit their use in specific patient populations and/or negatively impact patient compliance with therapy. Developing improved therapies requires diversifying our understanding of the mechanisms underlying postnatal bone remodeling by examining lesser-known signaling pathways. One such pathway is the taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors, which participates in monitoring energy and nutrient status. Previous work reported that global deletion of TAS1R member 3 (TAS1R3), which is a bi-functional protein that recognizes amino acids or sweet molecules when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively, leads to increased cortical bone mass. Here, we corroborate the increased thickness of cortical bone in Tas1R3 knockout mice and confirm that Tas1R3 is expressed in the bone environment. Quantification of serum bone turnover markers indicate that this phenotype is likely due to uncoupled bone remodeling, with levels of the bone resorption marker CTx being reduced greater than 60% in Tas1R3 mutant mice; no changes were observed in levels of the bone formation marker PINP. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and RAW264.7 cells following RANKL-mediated differentiation. These findings suggest that osteoclast function and/or differentiation may be altered in the absence of Tas1R3 expression. To test this, we quantified bone-specific expression of Rankl and determined the Rankl:Opg ratio; no differences were observed between control and Tas1R3 knockout mice in these analyses. In vitro studies examining further downstream effectors of TAS1R2:3 in response to saccharin and receptor antagonist gurmarin are currently underway. Collectively, our findings provide the first demonstration that nutrient monitoring by TAS1R3 is essential for normal bone resorption in vivo.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
Mot-clé:
PTH / Wnt signaling pathways, heterotrimeric G protein-coupled receptors, low bone mass, taste receptor type 1 (TAS1R), and postnatal bone remodeling
date créée:
11/10/2017

184. Osteocyte-Specific Deletion of the α2δ1 Auxiliary Voltage Sensitive Calcium Channel Subunit

Title Tesim:
Osteocyte-Specific Deletion of the α2δ1 Auxiliary Voltage Sensitive Calcium Channel Subunit
Créateur:
Yi, Xin, Schneider, Artur, Wright, Christian, Hum, Julia, and Thompson, William
La description:
Context: Skeletal unloading due to disuse, disease, or aging increases bone loss and the risk of skeletal fracture. Conversely, mechanical loading is anabolic to the skeleton, promoting skeletal integrity through increased bone formation. As calcium influx is the first measurable response of bone cells to mechanical stimuli, voltage sensitive calcium channels (VSCCs) play a critical role in bone formation. Given VSCC activity is influenced by its auxiliary α2δ1 subunit, regulating the gating kinetics of the channel’s pore-forming (α1) subunit and forward trafficking of VSCCs to cell membranes, the α2δ1 subunit may govern anabolic bone responses. Objective & Design: We hypothesized that osteocyte-specific α2δ1 deletion in a mouse model would impair skeletal development, decrease bone formation and mechanosensitivity. Methods: Generation of an osteocyte-specific α2δ1 knockout was accomplished by crossing mice (C57BL/6) harboring LoxP sequences flanking Cacna2d1, the gene encoding α2δ1, with mice expressing Cre recombinase under the control of the Dmp1 (10Kb) promoter (Cacna2d1fl/fl, Dmp1-Cre+). To assess skeletal phenotype and mechanosensitivity, longitudinal whole body and site-specific DXA, in vivo μCT (10wk old), and two weeks of tibial loading (16wks) will be conducted before femurs are collected at 20 wks for mechanical testing, ex vivo μCT, and quantitative histomorphometry. Results & Conclusion: Preliminary analyses show no differences in whole body or site-specific BMD and BMC values between mice over time, suggesting osteocyte-specific α2δ1 deletion may not influence skeletal development. However, key differences in mechanosensitivity following tibial loading are expected given the potential role of α2δ1 in mechanically-induced bone formation.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
date créée:
11/9/2018

185. Osteopathic Medicine Supportive Care in Pediatric Oncology - A Pilot Study

Title Tesim:
Osteopathic Medicine Supportive Care in Pediatric Oncology - A Pilot Study
Créateur:
Belsky, Jennifer, Stanek, Joseph , and Arand, Amanda
Related Url Tesim:
Audio presentation available: https://marian.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=933afcdf-420a-4cfe-bbb5-adf7011b60e9
La description:
Chemotherapeutic agents, such as vincristine, are well known antineoplastic and cytotoxic drugs, affecting patients broadly during treatment of cancer. Well known side effects, such as constipation and neuropathic pain, affect the quality of life of these patients recovering from cancer as well as its treatment. An option that alleviates troublesome side effects while still allowing the treatment to work would assist patients with wellbeing and comfort. Osteopathic manipulative treatments (OMT) are often utilized for various ailments in both pediatric and adult populations. A previous pilot study investigated the safety and feasibility of OMT in pediatric oncology patients and reported no serious adverse events attributed to OMT intervention. We hypothesized that OMT intervention during cancer therapy will improve constipation and neuropathic pain for children with leukemia undergoing chemotherapy.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
Poster
Mot-clé:
leukemia, Osteopathic manipulative treatments (OMT), Pediatric Oncology, and Osteopathic Medicine
date créée:
2021

186. Outcomes in Blunt Cerebrovascular Injury Following the Use of an Evidence-Based Treatment Protocol

Title Tesim:
Outcomes in Blunt Cerebrovascular Injury Following the Use of an Evidence-Based Treatment Protocol
Créateur:
Melillo, AP, Leipzig, TJ, Sahlein, DH, Kovanda, TJ, Jacobson, LE, Rodgers, RB, and Freeman, ZA
La description:
Blunt cerebrovascular injury (BCVI) is rare but has been identified in trauma victims with increasing frequency in recent years due to improvements in imaging techniques and screening protocols. The incidence of BCVI is believed to be about 1% in blunt trauma victims. Multiple different criteria have been established for BCVI screening. BCVI is graded according to severity of vessel injury1. Treatment varies by institution, ranging from observation to the use of antiplatelet or anticoagulant agents. Due to the rarity of these injuries, optimal treatment is not yet known and most treatment strategies are based on retrospective reviews with poor patient follow up for outcome measures. Goodman Campbell Brain and Spine (GCBS) has developed an evidence-based treatment protocol for managing BCVI. In this study, the authors present data regarding outcomes for BCVI patients managed at a level I trauma center using this treatment algorithm.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
Mot-clé:
Goodman Campbell Brain and Spine (GCBS), trauma victims, severity of vessel injury1, and Blunt cerebrovascular injury (BCVI)
date créée:
11/10/2017

187. Outcomes Using the Reinforced Biologic Augmented Repair (ReBAR) Technique in Robotic Transabdominal Preperitoneal Ventral Hernia Repair

Title Tesim:
Outcomes Using the Reinforced Biologic Augmented Repair (ReBAR) Technique in Robotic Transabdominal Preperitoneal Ventral Hernia Repair
Créateur:
Sowers, Briana , Banaschak, Cory , and Szotek, Paul
Related Url Tesim:
Audio Presentation: https://marian.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=30d9f6a9-3c8d-4613-8f9e-adf7011bad4b
La description:
Due to the availability of information on the internet, patients are well informed of the several types of hernia repair available to them. They are also increasingly made aware of the litigious environment surrounding synthetic mesh use through advertising [1]. With increasing concern for complications, patients are seeking methods of hernia repair that reduce foreign material while providing lasting results. In response to patients’ concerns, we developed a novel technique known as the reinforced biologic augmented repair (ReBAR), which incorporates data proven principles of hernia repair. This includes (1) primary closure of hernia defects and (2) reinforcement of the primary repair using mesh (figure 1). These principles have been proven to decrease ventral hernia recurrence rates [2,3]. The purpose of this study is to analyze the postoperative outcomes in robotic assisted reinforced biologic augmented repair of ventral hernias. The primary outcome is ventral hernia recurrence. Secondary outcome was incidence of surgical site occurrence.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
Poster
Mot-clé:
Reinforced Biologic Augmented Repair Technique, Transabdominal Preperitoneal Ventral Hernia Repair, and Robotic
date créée:
2021

188. Paclitaxel Dose in iPSC-Generated Sensory Neurons for Ex Vivo Modeling of Taxane-Induced Peripheral Neuropathy

Title Tesim:
Paclitaxel Dose in iPSC-Generated Sensory Neurons for Ex Vivo Modeling of Taxane-Induced Peripheral Neuropathy
Créateur:
Wu, Xi, Schneider, Bryan, Yadav, Rina, Gardner, Laura, Shen, Fei, and Cunningham, Geneva
La description:
Purpose: To establish an ex vivo model of paclitaxel induced peripheral neuropathy that can be translated clinically using induced human neurons. Experimental Design: Human induced pluripotent stem cells (iPSCs) will be differentiated into mature sensory neurons. After reaching maturation, neurons will be treated with varying doses (0nM, 25nM, 50nM, and 75nM) of paclitaxel to identify the ideal concentration to model paclitaxel-induced peripheral neuropathy ex vivo. Various phenotypic changes will be assessed including changes in morphology, viability, number of dendritic processes, and sensory marker expression patterns. Results: Paclitaxel dosing at 25 nM allows for a 23% reduction in processes length (p=0.04), 50 nM and 75 nM allow for a 51% and 59% reduction in process length (respectively, p<0.0001) while maintaining viable neurons. Conclusion: The administration of 50 nM of paclitaxel to iPSC derived neurons presents an ex vivo method to model paclitaxel induced neuropathy in patients that receive 80 mg/m2 of weekly paclitaxel.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
date créée:
11/9/2018

189. Papillary glioneuronal tumor presenting with low-pressure hydrocephalus from intraventricular spread: Case Report

Title Tesim:
Papillary glioneuronal tumor presenting with low-pressure hydrocephalus from intraventricular spread: Case Report
Créateur:
Myers, Nicholas A., Marker, D., Shah, K., Payner, T., and Kulwin, C.
Donateur:
Department of Pathology, University of Pittsburgh Medical Center, Goodman Campbell Brain and Spine, and Ascension St. Vincent Hospital
La description:
Papillary glioneuronal tumors (PGNTs) are rare, benign neoplasms that are typically solid or solid/cystic, well-circumscribed, parenchymal, solitary, and calcify. While intraventricular location, tumoral hemorrhage, and/or high-pressure obstructive hydrocephalus have been described, presentation with multifocal disease and normal pressure hydrocephalus (NPH)-like symptoms has not. We describe the novel presentation of a glioneuronal tumor distinctly presenting with NPH-like symptoms from intraventricular spread and the associated management.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
Additional information:
Images from the published report in Radiology Case Reports Volume 18, Issue 10, October 2023, Pages 3632-3635
La langue:
English
Type:
Poster
Mot-clé:
Papillary glioneuronal tumors (PGNTs), neoplasms , multifocal disease , normal pressure hydrocephalus (NPH), and glioneuronal tumor
date créée:
2023

190. Passing of the TORCH: A Medical, Historical, and Social Comparison between Rubella and Zika

Title Tesim:
Passing of the TORCH: A Medical, Historical, and Social Comparison between Rubella and Zika
Créateur:
Marcus, Peter and Pham, Nhat
Related Url Tesim:
Audio presentation: https://marian.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=50539a1d-215e-4d8f-9cae-ac74003f5445
La description:
Rubella was first described in the 1750s but took until 1941 when Congenital Rubella Syndrome was characterized to become medically significant. Similarly, zika virus was discovered in 1947 but only made headlines in 2016 when its infection during pregnancy was associated with fetal microcephaly. Interestingly, despite zika being primarily a disease of the developing world and rubella historically being a world wide disease. Zika was found to have been studied and controlled al a much faster rate than rubella - particularly in the United Slates (U.S.). This correlation is further highlighted by the fact that there are currently no therapies or vaccines available for zika. A review of Thomas McKeown's work, the McKeown Thesis, provides insight into the U.S.'s successful zika control. The Thesis posits that broad based social efforts at the population level are more significant at affecting public health than narrow•based medical interventions at the individual level. The swift control of zika despite the lack of specific therapeutics suggests the McKeown Thesis's applications. This presentation will reflect on the progress and history of medicine within the past century and demonstrate the need for continued vigilance within the medical community.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
Poster
Mot-clé:
Zika virus, McKeown Thesis, and Rubella virus
date créée:
2020