2022 VCOM Research Retreat Program

RESEARCH RETREAT 8th Annual

VCOM CAROLINAS NOVEMBER 11 - 13, 2022

WELCOME

The Research Department, Provost Rawlins, and Chairman Rocovich are pleased to welcome you to the 2022 VCOM Research Retreat. This annual event has become a cornerstone for the continuous growth of the VCOM research environment. It provides an ideal opportunity for faculty to become better acquainted with the unique research capacities, resources, and opportunities available across the VCOM four-campus system. Key priorities for the 2022 Research Retreat include building new interdisciplinary networks and enhancing collaborations among scientists and clinicians at the VCOM Auburn, Carolinas, Louisiana, and Virginia campus locations, clinical partners, and colleagues at associated institutions of higher education. Our goal is to bring great minds together across VCOM's geographic reach, inspire innovative new research ventures, and lay the groundwork to support and sustain these cross-campus partnerships. This year's sessions balance in-depth topical discussions and practical tips and considerations for conducting research in an ever-evolving context. Three Keynotes bridge the biomedical and clinical research fields in addressing how to take innovations from bench to bedside. On Saturday morning, Brian Rood, MD, will discuss "Applied Proteo(geno)mics in Pediatric Brain Tumors." In the afternoon on Saturday, Joel Stitzel Jr., PhD will present "Human Body Modeling Update and Application to Medical Research." The final keynote will be held on Sunday morning, featuring Sam Konduros, JD, speaking about "The Rapid Evolution of Life Sciences and Healthcare Innovation in the Carolinas (and Beyond)." Panel sessions will provide knowledge resources and discussions to strengthen skills in the areas of Conducting Systematic Medical Literature Reviews and Regulatory Issues in Human Subjects Research. A third panel session will provide concepts and tools to support student mentorship in research, with the launch of VCOM's new third year Research Rotation and growth of the DO with Research Distinction program. Three educational sessions will be dedicated to exploring different areas, such as Biostatistics and its Medical Oriented Process, How to Conduct Medical Research in a Busy Clinical Practice, and VCOM Protocols and Processes for Student Research Mentorship. Breakout networking activities, MEDx talks, and a research poster session provide opportunities for VCOM's established and early-career researchers and partners to share their recent initiatives, projects, and plans that will hopefully spark new collaborations across the VCOM four-campus system. This year, over 120 registered attendees will join us for the weekend. We hope that researchers will find themselves enlightened by the perspectives and experiences shared by their peers and energized by new insights into the abundant opportunities, directions, and research developments available in the current climate. A special thank you to Dean Cannon and the Carolinas campus administration for hosting and overseeing the logistics to make this event possible. We look forward to learning and working with you during the 2022 Research Retreat!

2022 VCOM Research Retreat Agenda

Friday, November 11 th DuPre House 6:00 – 8:30pm

Reception Dinner

6:30pm

Welcome to VCOM-Carolinas

Matthew Cannon, DO, Dean for Carolinas Campus

Saturday, November 12 th VCOM-Carolinas 7:00 – 8:30am 3 rd Floor Seminar Rms

Breakfast/Welcome

8:30 – 8:45am Lecture Hall I 8:45 – 9:45am Lecture Hall I 9:45 – 10:00am 10:00 – 10:15am Lecture Hall I

State of Biomedical Research Processes at VCOM .25 CME available Morning Keynote: Applied Proteo(geno)mics in Pediatric Brain Tumors *This is not a designated CME Program* VCOM Protocols and Processes for Student Research Mentorship .25 CME available 3 rd Year Medical Student Research Rotation and DO with Research Distinction .75 CME available Break

P. Gunnar Brolinson, DO

Brian Rood, MD, Professor of Pediatrics in the Center for Cancer and Blood Disorders, Children's National Hospital

Dixie Tooke-Rawlins, DO P. Gunnar Brolinson, DO

Harold “Skip” Garner, PhD Lindsay Tjiattas-Saleski, DO, Kayla Afkinich, BA

10:15 – 11:00am Lecture Hall I

11:00am – 12:00pm* Lecture Halls Student Lounges Conference Rooms

Research Networking Session Breakout Rooms • Basic Science Research (Lecture Hall I) • Educational Research (Room 252)

Room Facilitators: •

James Mahaney, PhD Larissa Collier, PhD Ron Januchowski, DO Alexis Stoner, PhD, MPH

• • •

• Clinical and Translational Research (Lecture Hall II) • Community-based & Population Health Research (Room 352) • OMM & Musculoskeletal Research (Room 343/344) • Open Rooms Available for Discussion (SGR Rooms) *This is not a designated CME Program*

•

P. Gunnar Brolinson, DO

12:00pm – 1:00pm* † 3 rd Floor Seminar Rms

Lunch

1:00 – 1:30pm Lecture Hall I

Afternoon Keynote: Human Body Modeling Update and Application to Medical Research .50 CME available

Joel Stitzel Jr., PhD, Professor, Biomedical Engineering, Wake Forest School of Medicine Panelists: P. Gunnar Brolinson, DO; Pam VandeVord, PhD, Associate Dean of Research and Innovation, Virginia Tech College of Engineering Alexis Stoner, PhD, MPH Panelists: James Mahaney, Tom Lindsey, DO, Elaine Powers, MSLS

1:30 – 2:15pm Lecture Hall I

Conducting Systematic Medical Literature Reviews for Faculty .75 CME available

2:15 – 2:30pm 2:30 – 3:30pm Lecture Hall II

Break

Melissa Lipsmeyer, PhD Joshua Hollingsworth, PharmD, PhD

VCOM MEDx talks *This is not a designated CME Program*

K Adam Morrow, PhD Kenny Brock, DVM, PhD

David Redden, PhD Lin Kang, PhD

3:30 – 4:30pm Lecture Hall I 4:30 – 6:30pm DuPre House

Biostatistics (Medical-oriented Processes) 1 CME available Poster Session and Reception *This is not a designated CME Program*

Facilitator: Harold “Skip” Garner, PhD

* Simulation and Technology Center All Campus Meeting; Room 116, 11:00am – 1:00pm † Clinical Faculty All Campus Meeting, Room 227, 12:00 – 1:00pm

2022 VCOM Research Retreat Agenda

Sunday, November 13 th VCOM-Carolinas 7:00 – 8:00am 3 rd Floor Seminar Rms

Breakfast

8:00 – 8:30am Lecture Hall I

VCOM-Carolinas Research Resources & Regional Healthcare System and University Partnerships for Faculty, Residents and Fellows .50 CME available Sunday Keynote: The Rapid Evolution of Life Sciences and Healthcare Innovation in the Carolinas (and Beyond) *This is not a designated CME Program*

Matthew Cannon, DO

8:30 – 9:15am Lecture Hall I

Sam Konduros, JD, President/Founder, SK Strategies LLC

9:15 – 9:30am

Break

9:30 – 10:15am Lecture Hall II

VCOM MEDx talks *This is not a designated CME Program*

Bidyut Mohanty, PhD Jonathan Millard, PhD Harold “Skip” Garner, PhD

David Moore, DVM, Associate Professor Emeritus, Virginia Tech Panelists: P. Gunnar Brolinson, DO, Kenny Brock, DVM, PhD, Harold “Skip” Garner, PhD, James Mahaney, PhD, Pawel Michalak, PhD Lisa Carroll, MD Panelists: P. Gunnar Brolinson, DO, Hanna Sahhar, MD,

10:15 – 11:00am Lecture Hall I

Regulatory Issues in Human Subjects Research at VCOM .75 CME available

11:00am – 12:00pm Lecture Hall I

How to Conduct Medical Research in a Busy Clinical Practice 1.0 CME available

12:00 – 12:15pm Lecture Hall I

Closing remarks – Main takeaways (general)

P. Gunnar Brolinson, DO

Accreditation Statement This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the American Osteopathic Association and Edward Via College of Osteopathic Medicine. The American Osteopathic Association is accredited by the ACCME to provide continuing medical education for physicians. AMA Credit Designation Statement – Physicians The American Osteopathic Association designates this live activity for a maximum of 5.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Brian R. Rood, MD Director , Cl inical Neuro-Oncology Medical Director , Brain Tumor Inst i tute Oncologist Chi ldren’ s Nat ional Hospi tal KEYNOTE

Dr. Brian R. Rood is the Medical Director of the Neuro-Oncology Program in the Brain Tumor Institute at Children’s National Hospital and a principal investigator in the Center for Cancer and Immunology Research at Children's National Research Institute. He is also Professor of Pediatrics at the George Washington University School of Medicine and Health Sciences and Adjunct Professor at the Fralin Biomedical Research Institute at Virginia Tech. He received a BA in English Literature from The Pennsylvania State University and an MD from Jefferson Medical College. He completed his pediatric residency training at the University of Vermont. He received his pediatric Hematology/Oncology training at Children's National Hospital and also completed a research fellowship in the molecular biology of pediatric brain tumors at the Children’s Research Institute. Currently, Dr. Rood’s research focuses on the application of proteomics in cancer biology investigation, neoantigen identification and biomarker development. He has also been studying the contribution of germline microsatellite genotypes to pediatric brain tumor predisposition. He currently serves as the Executive Co-Chair of the Children’s Brain Tumor Network, an international consortium of 26 institutions that maintains the world’s largest pediatric brain tumor tissue and data repository which are freely provided to the research community to support the development of ground-breaking clinical trials through data-driven precision medicine.

Joel Douglas Stitzel Jr. , PhD Professor , Biomedical Engineering Wake Forest Universi ty School of Medicine KEYNOTE

Joel Stitzel, PhD, earned his master’s degree in biomedical engineering in 2000 from the Medical College of Virginia and Virginia Commonwealth University and his doctorate in mechanical engineering in 2003 from Virginia Polytechnic Institute and State University. While completing his doctorate, he helped establish an impact biomechanics laboratory at Virginia Tech, which expanded into the Virginia Tech – Wake Forest Center for Injury Biomechanics when he moved to Wake Forest in 2003. Early in his research, Joel Stitzel developed expertise in the computational modeling of the human body. He played a key role in Toyota’s Total Human Model for Safety (THUMS) model and developed improved body models that more accurately reflect soft tissue injuries, such as lung and brain injuries. Under his direction, Wake Forest became the integration center for the Global Human Body Model Consortium (GHBMC), coordinating researchers who developed one of the world’s most biofidelic human body models for a global consortium of automotive manufacturers and suppliers. Stitzel’s interest in injury mechanics brought Wake Forest to cutting-edge research into automotive safety. In 2004, he developed the biomedical engineering department, in collaboration with acute care and orthopedic surgery, into a Crash Injury Research and Engineering Network (CIREN) center that contributes data to national databases on automotive collision injuries and modern safety systems. His team is also developing an Automatic Crash Notification (ACN) system, an algorithm that will quantify specific features of injuries and improve triage decisions. Stitzel believes that his research can impact many people by reducing the burden, morbidity, and disability of injuries. To further this goal, he facilitates relationships between the biomedical engineering department and industry sponsors, academic institutions, and other research entities. By collaborating with industry partners, he can ask research questions with real-world implications for injury prevention and treatment that result in products that integrate into current practices quickly, reducing the burden of injury. Working with industry also allows Stitzel to apply creativity to complex problems. He enjoys working with industry partners to solve their thorniest problems. Collaboration, he believes, is the key to solving these challenges, and he has deep experience in developing teams with the right expertise to make a project succeed. Wake Forest, he believes, is the perfect place to assemble multidisciplinary teams of creative and experienced experts to tackle research challenges.

Sam Konduros, JD President/Founder , SK Strategies LLC KEYNOTE

Konduros, a licensed attorney since 1990, founded SK Strategies in 2004 – an SC-based consulting firm specializing in economic development, strategic planning, championing major corporate initiatives, public-private partnerships, integrated marketing & business development strategies, innovation, and vision-mission-brand development. He has a demonstrated track record and specialization in industries ranging from advanced manufacturing to healthcare and life sciences. Current major SK Strategies clients include the United States Performance Center, Good Growth Capital, and Southeast Life Sciences. Following an 11-year affiliation with Greenville Health System (now Prisma Health), Konduros served as President/CEO of SCBIO (South Carolina Biotechnology Industry Organization). In that leadership role, he focused on scaling up and leading the innovative trade organization to its next level of development, working closely with strategic partners from industry, academia, and the public/private sector. SCBIO’s core mission areas included spearheading high-impact initiatives in economic development, advocacy, integrated marketing, innovation/R&D, convening stakeholders, capital attraction, and ultimately helping to improve healthcare delivery. Konduros was also recruited to serve as President/CEO of KOR Medical in 2021 and on the Vikor Scientific Board of Directors. As CEO, he led efforts to rapidly and strategically build and develop the innovative personalized medicine-focused clinical cannabis life sciences company and ensure a successful launch of its initial national product portfolio within seven months as the newest division of Vikor. Konduros currently serves on the South Carolina Chamber of Commerce Board & Executive Committee, South State Bank’s Greenville Advisory Board, and the Palmetto Conservation Foundation Board. He has recently served on the Southeast US Life Sciences Association Board, the Carolinas Healthcare Innovation & Technology Association Advisory Council, and SC Research Authority Biotech Innovation Advisory Council. Konduros received the Order of the Palmetto from SC Governor Henry McMaster in 2017 (SC’s highest civilian honor), was named to Greenville’s 50 Most Influential People Hall of Fame in 2019, the Chairman’s Award for the Greater Greenville Chamber of Commerce (2008 & 2010), was formally designated as a Knowledge Economist by the South Carolina Research Authority (2007) and was named a South Carolina Ambassador for Economic Development by Governor Jim Hodges (2001). In addition to his current leadership roles, Konduros has also served on the South Carolina Independent Colleges & Universities Board of Directors, Clemson University’s College of Business & Behavioral Science Advisory Board, as Vice Chair for the Board of the American Red Cross Upstate SC Chapter, and as Chair of the Upstate SC Air Service Partnership Committee on behalf of GSP International Airport. Konduros is a graduate of Clemson University (1985 magna cum laude, Rhodes Scholar finalist), the University of South Carolina School of Law (1989), and the University of Oklahoma Economic Development Institute (1993). Additionally, Konduros obtained his real estate license in 2012. He has been married for 27 years to Aphrodite Konduros, an SC Appellate Court Judge, and they reside in Greenville and Charleston, South Carolina. He enjoys mentoring young adults & executives and pursues an active spiritual life. He is an avid snow skier, world traveler, outdoorsman and workout enthusiast, amateur landscaper, and photographer, and he has ridden his motorcycle across the United States.

MEDx TALKS

Jonathan Mi l lard, PhD VCOM - Virginia Applying Shape Analysis to Cl inical Problems

Mel issa Lipsmeyer, PhD VCOM - Louisiana Trust ing your gut : how our gut microbiome inf luences heal th and disease

Harold "Skip" Garner, PhD VCOM - Carol inas Syndromic Survei l lance

Adam Morrow, PhD VCOM - Louisiana Tau: I t ’ s Al l Greek to Me

Joshua Hol l ingsworth, PharmD, PhD VCOM - Auburn Heal th Behavior Change Programs: Helping Doctors Help Pat ients

Kenny Brock, DVM, PhD VCOM - Auburn One Heal th Medicine

Bidyut Mohanty, PhD VCOM - Carol inas DNA isn’ t just what we thought i t was

ABSTRACTS

Characterizing Molecular Mechanisms that Mutant Proteins Promote Cancer Progression Presenter: Lin Kang, PhD Co-Authors: Md Saqline Mostaq; Amanda Raphael; Celine Asbury*; Anish Gupta; Yong-Yu Liu, MD, Phd Mutant proteins of cancer-addicted genes (such as TP53 and KRAS) promote cancer progression in metastases and cause cancer resistance to treatments. However, it is still unclear how the expression of mutant proteins is upregulated and further promotes the enrichment of cancer stem cells in tumors under chemotherapy. In response to the challenges of anticancer drugs, increased ceramide glycosylation catalyzed by glucosylceramide (GCS) confers cancer drug resistance and enriches cancer stem cells. We established UGCG knock-out cell models and characterized the correlation of ceramide-glycosylation to tumor progression. The Human UGCG gene that encodes GCS, a limiting enzyme catalyzing the first reaction of ceramide glycosylation, was knocked out in colorectal cancer cell lines of WiDr (TP53 R273H+/+) and LS1747 (KRAS G12A+/-) via CRISP/cas9 gene editing. We found that knock-out of UGCG significantly decreased GCS activity, the EC50 values of oxaliplatin, and tumorgenicity of WiDr/UGCG-KO cancer cells, and further re-sensitized tumor generated from WiDr/UGCG-KC cells response to oxaliplatin treatments. Based on single nucleus-RNA sequencing (snRNA-seq), we will be able to characterize various cell populations during the propagation of cancer stem cells in tumors under chemotherapy. Further assessment and genomic analyses of snRNA-seq with typical RNA-seq of tumors will help us to characterize molecular mechanisms that regulate the cancerous pluripotency, formation, and differentiation of cancer stem cells from tumors under chemotherapy. Colorectal cancer (CRC) is the fourth most common type of cancer and the second leading cause of cancer-related deaths in the United States. One pathway that is heavily implicated in CRC is NF-kB, a master transcriptional regulator of genes related to proliferation, survival, immunity, and inflammation. Previous studies have demonstrated the anti-inflammatory and anti-neoplastic role of the canonical NF-kB signaling pathway in CRC. NF-kB is extensively down regulated in CRC of both mice and humans. However, relatively little is known about the non-canonical NF-kB signaling cascade (activation of Nik). To further understand NF-kB/Nik involvement in colon cancer development and progression, we will grow murine intestinal organoids extracted from wild-type (Nikloxp), Nik-/-, Nikloxp/Villiancre, and Villiancre mice and characterize their growth and development in comparison with WT. Our research hopes to further characterize this aggressive and deadly disease. We hypothesize that loss of non-canonical NFκB signaling attenuates stem cell regeneration of the epithelial cell barrier and/or inhibits cell death in mature epithelial cells in the colon. We further postulate that either of these events is significant contributor to the progression of colorectal cancer and may contribute to tumorigenesis through either a stem cell or enterocyte-dependent mechanism. We hope to further identify the cell composition and 3D architecture of these NF-kB low organoids to better understand how NF-kB is implicated in the development of CRC Role of Noncanonical NF-kB Signaling in the Development of Intestinal Cell Subpopulations Presenter: Stephan Brown, MD, PhD Co-Authors: Creighton Kellogg*; Mandy Stallard*; Katherine Hanson, MS; Holly Morrison*; Irving Allen, PhD

*VCOM Student

Abstracts

Pediatric Intensive Care Unit Boot Camp: A Preparatory Course for Intern Year Presenter: Hannah Sahhar, MD Co-Authors: Vivian Louviere*; Lauren Dunn*; Nicholas Gavin*

Introduction: Medical schools today have an emphasis on adult care within their educational program. Although the third year of medical school incorporates a pediatric rotation, there is minimal training to prepare students for the pediatric intensive care unit (PICU). In response to this deficit within the curriculum, a preparatory PICU boot camp was developed. The boot camp was made up of a variety of learning experiences including case-based interactive lectures in electrolyte and fluid balance, status epilepticus, status asthmaticus, and diabetic ketoacidosis. Students also participated in workshops for procedural skills in mechanical ventilation and lumbar puncture. Lastly, students engaged in high fidelity simulations managing hypovolemic, cardiogenic, adrenal, and septic shock. Objective: The goal of this project was to establish the effectiveness and benefit of completing the boot camp prior to intern year. Methods: A total of 50 osteopathic medical students during their 4th year rotation in PICU participated in the course and the study. The students’ knowledge was assessed using a pre-test and post-test from the day of the boot camp. Students' feedback was also utilized to evaluate the boot camp’s quality. A survey will be administered mid way through intern year to evaluate if the graduated students believe the boot camp prepared them for residency. Available results of the study were analyzed using IBM SPSS Statistics software. Paired-Samples T-Test was used to assess the differences between mean scores for pre and post-tests. One-Sample T-Test was used to assess Likert scale satisfaction survey mean scores for individual course modules. A significance level of α = 0.05 was used to demonstrate a difference between the mean scores. Results: Data collected on the day of the camp showed there was a significant difference between mean scores of pre and post-tests; 8.86 versus 9.43 respectively (p-value= 0.002 and 95% Confidence interval (CI) of the difference 0.22-0.92); this demonstrates a statistically significant improvement of knowledge following the camp. Students were then asked to rate each learning experience using a Likert-scale survey of scale 1-10. The mean score of course satisfaction for individual modules and sessions ranged from 9.2 (95% CI: 8.83-9.57) to 9.66 (95% CI: 9.45-9.87) with all p-values Local and systemic inflammatory response in open-abdomen surgeries using vacuum-assisted closure with or without continuous irrigation direct peritoneal resuscitation. Presenter: Luciana Schwab, PhD Co-Authors: Jon Hagar, PhD; Patrick Fisher, PhD; TJ Mack, MSN; Caleb Mentzer, DO Sepsis accounts for 1 in 5 deaths worldwide. Abdominal sepsis in particular has an alarmingly high mortality rate, exceeding 30% in certain settings. Patients with abdominal sepsis often require multiple laparoscopic operations; to facilitate these repeat procedures, patient abdomens can be sealed temporarily between operating room visits with a vacuum-assisted closure (VAC) apparatus. At the operating surgeon’s discretion, continuous flushing with fluids (lavage) of the peritoneal cavity can be used in conjunction with VAC with the aim to improve local blood flow and help wash out inflammatory contents. Whether adjunctive lavage in fact improves patient outcomes or modulates immune parameters remains to be formally examined. Herein, we propose to examine clinical parameters, outcomes, and local and systemic immune activation over time in patients receiving VAC with or without continuous lavage. Our results will critically inform current treatment practices and the design of future large scale efficacy studies necessary to optimize patient care.

*VCOM Student

Abstracts

Presenter: Marilyn Malia, DO Co-Authors: Teresa Kilgore, DO

Preventing Mold in the Anatomy Lab Presenter: Tiffany Carpenetti, PhD Co-Authors: Aaron Beger, PhD Maintaining formalin-fixed cadavers through an entire year of dissection is challenging at best. Of the many trials faced, including fluid management, desiccation, and unique donor characteristics, mold is a constant threat. Our lab employs mold abatement procedures that vary depending on the extent of the spread. Superficial mold is treated with either 50/50 phenol/ethanol or 10 percent formalin on a cloth compress. Extensive spread is treated with both compresses and injections of Trinity Long Term Preservation (LTP) fluid, an arterial fluid containing a proprietary ratio of ethanol, formaldehyde, ethylene glycol, and glutaraldehyde. In addition to treating mold on the donors, body bags are cleaned with Cavicide – a quaternary ammonium disinfectant. Overall, the efforts to treat and prevent mold are based on experience and conjecture, with no history of controlled studies to support the protocols in place. To determine the most effective method of killing mold and preventing spread, mold was cultured from a donor and exposed to six disinfectants currently employed in the anatomy lab: Lysol (both concentrated and diluted 1:20 with tap water, which is used as a wetting solution), Trinity Wetting Solution, Trinity LTP fluid, Cavicide, Dis-spray (a disinfectant employed funeral homes), and a hydrogen peroxide-based disinfectant. Potato dextrose and Sabourand plates were inoculated with mold, and 7mm circles of filter paper were saturated with one disinfectant or tap water as a control and evenly spaced over the plates to determine inhibition levels. Of the six, only Dis-spray successfully prevented mold growth, with an established zone of inhibition that persisted for at least fourteen days. Additionally, a sample of the mold was sent to a medical microbiology facility for potential identification. Based on the results of this experiment, mold treatment and prevention strategies in the anatomy lab will include Dis-spray as a first-line defense. In 2016 the American Medical Association eliminated pain as a "fifth vital sign". In the same year, Morbidity and Mortality Weekly reported opioid-involved drug overdoses to be the most common cause of accidental death nationally. Presently, the opioid epidemic is a public health crisis with sufficient magnitude to impact the overall life-expectancy of the aforementioned population. The future of healthy and individualistic pain management in a variety of clinical settings requires considerations which update approaches to acute and chronic pain as the medical culture in the United States attempts to address the opiate epidemic, including an objective approach to pain. A search of computer databases was conducted from EBSCOhost including MEDLINE, as well as federated library search engines. Selection criteria was constrained to peer reviewed medical journal articles published between 1980 and 2022 relevant to the objective of this analysis, with an emphasis on contemporary articles. This review found that there is a plethora of considerations that may be effective in reducing the incidence of iatrogenic addiction and decreasing overall opioid use. Additionally, the literature revealed methodological errors in prior studies evaluating interventions which were not habit forming. A critical review of the literature explores the history of medical opioid use, the pharmacological spectrum of pain management, efficacy of available complementary and alternative medicine (CAM), psychological factors, the avoidance of iatrogenic addiction, and ultimately an objective approach to pain. Systematic Review of Pain Management with Proposed Non-opioid Treatment Algorithm and Objective Pain Measures

Abstracts

Intracellular Osteopontin in Pulmonary Arterial Hypertension Presenter: Rebekan Morrow, PhD Co-Authors: Reggie Skains*; Adam Morrow, PhD

Identifying Site-Specific Mutations that Increase SARS-CoV-2 Virulence using Selective Sweep Analysis Presenter: Stephen DiGiuseppe, PhD Co-Authors: Juan Guerra*; Nora Rady*; Kasia Michalak, MSc; Ariana Faraji*; Lin Kang, PhD; Pawel Michalak, PhD In 2019, the world was alerted to an emerging novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which poses a significant threat to global public health. Patients infected with SARS-CoV-2 experience mild to severe flu-like symptoms in the upper respiratory tract. While most infections will be cleared by the immune system, the virus can disseminate to the lower respiratory tract where patients may develop severe pneumonia and severe acute respiratory distress syndrome (ARDS), a life-threatening condition that requires patients to be intubated in intensive care. Fortunately, several vaccine candidates were approved for emergency use. Despite global deployment of multiple vaccines, continued outbreaks across the world suggest the pandemic is far from over. The origins of SARS-CoV-2 are still unknown, several bat- and pangolin-derived viruses were found to be closely related suggesting a zoonotic origin. The exact selective mutations that allowed SARS-CoV-2 to jump to humans is not well understood, but recent innovations in assays involving SARS-CoV-2 have provided insight into these mutations. Previous work examining these mutations in the SARS-CoV-2 genome through selective sweep analysis found that a non-synonymous change within the Spike protein receptor-binding domain increased binding to human ACE2, possibly contributing to its adaptive evolution. We hypothesize that site-specific mutations with adaptive sequence signatures in SARS-CoV-2 spike contribute to its increased affinity to human ACE2 receptor resulting in increased virulence. To safely study SARS-CoV-2 infectivity, we generated pseudovirus harboring SARS-CoV-2 Spike via a recombinant lentivirus system. The pseudovirus binds and enters cells expressing the human ACE2 receptor. Using the lentivirus system, we performed site-directed mutagenesis to mutate specific residues within the Spike gene with selective sweep signatures detected from SARS-CoV-2 genomes deposited in the GISAID EpiCov database. We generated pseudovirus harboring the wild-type or mutated Spike protein. We quantified the relative abundance of wild-type and mutant pseudovirus using specific primers by PCR. Next, we infected 293T cells expressing human ACE2 with wild-type and mutant pseudovirus and measured infectivity by relative luciferase activity and live-cell fluorescence imaging. In turn, we seek to identify specific mutations of the Spike protein that increase infectivity of SARS-CoV-2 pseudovirus to better understand how the native virus binds to ACE2 cells across different species, and determine which mutations govern changes in virulence. *VCOM Student Pulmonary arterial hypertension (PAH) is a progressive disease caused by narrowing of the pulmonary arteries, at least partially due to extracellular matrix remodeling and endothelial to mesenchymal transition (EndoMT). Osteopontin (OPN) is a protein involved in many cellular processes, including adhesion, migration, and modulation of the inflammatory response. The goal of this project was to determine whether loss of intracellular osteopontin enhances endothelial dysfunction in pulmonary artery endothelial cells (PAEC) in PAH. Previous data have shown that PAEC from an animal model of PAH exhibit lower levels of intracellular OPN than healthy controls. We generated stable OPN overexpressors and transfected PAEC with siRNA to transiently knock down OPN expression. RNA sequencing was performed as a screen for possible targets of interest. Protein levels were evaluated by western blot and ELISA. Contrary to expectations, PAH cells expressed higher levels of OPN and displayed increased markers of endothelial activation, possibly contributing to the inflammatory phenotype of this disease.

Abstracts

Geometric Morphometric Analysis of Clival Anatomy with Application in Approaches to the Posterior Cranial Fossa Presenter: Jonathan Millard, PhD Co-Authors: Kaivon Kouhestani*; Amanda Swaak*; Alexandra Luna*; Chelsea Bengson*; Benjamin Mann* INTRODUCTION: The posterior cranial fossa is an area of intense neurosurgical interest. The natural anatomical variability of the basicranial skeleton has been well described using dry skeletal collections; however, geometric analyses of soft tissues have not been thoroughly reported. The primary aims of this research are to quantify and characterize the three-dimensional relationships of the abducens (CN VI) and hypoglossal (CN XII) nerves in relationship to salient bony landmarks. METHODS: Typical dissection techniques were used to reveal the posterior cranial fossa on 34 formalin-fixed whole-body donors. A Microscribe® i+ 3D Digitizer Portable Coordinate Measuring Machine was used to register the location of eight 3D landmarks. Data were analyzed with MorphoJ v1.07a. Principal component (PC) analysis was used to explore variability in landmark configurations. RESULTS. PC analysis revealed four loadings capturing a total of 79.08% of the total shape variation in the sample. PC1 accounted for 31.55% of the shape variation and indicates a strong displacement in the inferolateral/superomedial axis of the CN VI dural meatus. PC2 captured 25.61% of the total shape variation and demonstrated lateral/medial displacement of all clival landmarks. There was a statistically significant difference between males and females along PC2 (p=.02). CONCLUSIONS: The lollipop diagram for PC1 shows substantial variability of CN VI’s penetration of the dura mater. This result is seen accompanied by a more superior and medial jugular tubercle. Interestingly, CN XII’s relative trajectory was very consistent along the first principal component. Graphical results of PC2 suggest a more platybasic morphology, with widened clival features and inferiorly recessed parasellar landmarks. In summary, CN VI is highly variable in its exit from the posterior cranial fossa, particularly when compared to CN XII egression. These findings should be considered when drilling the jugular tubercle. Future directions should include consideration of the geometric situation of Dorello's canal. We created and deployed an infectious disease surveillance web-based application based on an existing, operational system in use to track clinical patient encounters by medical trainees, thus providing real-time feedback on each student’s individual progress. This system, called CREDO (Clinical Rotation Evaluation and Documentation Organizer, https://credo.education/signage.html), has been in operation for over 3 years and has captured over 4 million diagnostic and procedural entries using WHO ICD-10 codes. Patient encounter information is gathered from over 1,300 clinics and hospitals across the Appalachian and Delta region states and Central America and the Caribbean (Honduras, El Salvador and the Dominican Republic). On our four campuses, we have over 6,000 users who have documented over 2,000,000 patient encounters. These system’s user interface runs on any browser-based hardware from a PC to smartphone. Data collection is centralized on a HIPAA compliant multi-instance cloud with a variety of spatial and temporal readouts, graphics, reports and automated alerts. A Syndromic Surveillance Tool for Early Detection and Monitoring of Emerging Infectious Diseases Presenter: Skip Garner, PhD Co-Authors: Cameron Sumpter, BS; Gabrielle Bruzda, DO; Fred Rawlins, DO

*VCOM Student

Abstracts

Presenter: Hannah Sahhar, MD Co-Authors: Abby Kabo*; Emma Hand*

Pediatric and Neonatal Boot Camp: A Preparatory Course for Pediatric Clinical Rotations Introduction: In the preclinical years, students do not get as much exposure to pediatric patients. The first experience with a pediatric patient is usually during their pediatric clinical rotation. Most clinical skills are taught based on the adult patient, leaving out the pediatric perspective and its unique aspects. Without prior exposure to this specific population, students are not as prepared for their pediatric rotation as compared to adult patients on their rotations. The Pediatric and Neonatal Boot Camp was designed to give second-year osteopathic medical students hands-on pediatric training. The course included interactive learning in the form of medical educational games, standardized pediatric patient encounters, high-fidelity simulations, and hands-on procedural clinical skills. Objective: This research project will determine whether there is a benefit for second-year osteopathic medical students to take a pediatric and neonatal boot camp course to prepare them for pediatric clinical rotations. Ultimately, we seek to establish whether exposure to pediatric specific clinical skills should be a part of the second-year curriculum. Methods: A pilot course in April 2021 involved 23 students from Edward Via College of Osteopathic Medicine- Carolinas campus. It included interactive learning in the form of medical educational games, standardized pediatric patient encounters, high-fidelity simulations, and hands-on procedural clinical skills. Pre- and post-tests were administered to the students at the beginning and end of the course. We used the de-identified results of those tests to compare and analyze the average test scores to determine if the course was successful in teaching them the predetermined objectives. Students’ feedback was also utilized to evaluate the boot camp’s quality directly after the course. We also plan to anonymously survey the students upon completion of their third-year pediatric clinical rotations to gain an understanding on whether they felt the boot camp course prepared them well for the pediatrics clinical setting. Results of the study were analyzed using IBM SPSS Statistics software. Paired-Samples T-Test was used to assess the differences between mean scores for pre- and post-tests. One-Sample T-Test was used to assess Likert scale satisfaction survey mean scores for individual course modules. A significance level of α = 0.05 was used to demonstrate a difference between the mean scores. Results: There was a significant difference between mean scores of pre- and post-tests; 6.86 versus 8.05 respectively (p-value= 0.001 and 95% Confidence Interval (CI) of the difference 0.51-1.83); this demonstrates a statistically significant improvement of knowledge following the camp. Using a Likert-scale survey of scale 1-10, the mean score of course satisfaction for individual modules and sessions ranged from 8.43 (95% CI: 7.65-9.21) to 9.57 (95% CI: 9.25-9.88) with all p-values

Resources for Osteopathic Medicine Presenter: Elaine Powers, MSLS Co-Authors: Jessica Muller, MA

Background: Collection development for Colleges of Osteopathic Medicine (COMs) has been a challenge since strictly osteopathic resources are somewhat specialized in regard to content and acquisition. Description: This poster will present a list of textbooks and journals needed to develop an osteopathic library collection. Organizations and publishers with osteopathic resources will also be described. Conclusions: A “top ten” list of osteopathic titles as well as a comprehensive list of osteopathic books and resources provide collection development guidelines for Colleges of Osteopathic Medicine as well as for librarians in other types of medical facilities. Creation of a QR code will provide access to the lists of resources.

*VCOM Student

Abstracts

Presenter: Steven Enkemann, PhD Co-Authors: Akshay B. Ratnai*; Brooke D. Escoe*

A Powerful Point-of-Care Clinical Aid in the Diagnosis of Vaginosis and STIs Vaginitis is the most common gynecological condition encountered in the OB/GYN offices today. It is diagnosed based on symptoms of abnormal discharge, pH, WHIF test, and/or observation of increased abnormal bacteria, yeast, or STIs such as trichomoniasis. The most common causes of vaginitis (90%) in symptomatic women are bacterial vaginosis (BV) (40-45%), vaginal candidiasis (CV) (20-25%), and trichomoniasis (TV) (15-20%). Yet up to 72% of women with vaginitis remain undiagnosed; 40% of yeast infections are misdiagnosed and 30% of bacterial infections require a 2nd office visit. This underlines the need for a rapid diagnostic tool that can accurately assess the health of a patient's microbiome in a cost and time effective manner. Caza Health has developed a point-of-care test (DayZ- Vaginal Health Assessment) designed to be performed in the physician office using a vaginal swab sample while the patient waits; thereby, allowing the appropriate treatment to be prescribed at the time of the office/clinic visit. The test uses the nCyte-AI automated scanning fluorescent microscope platform, which provides a fluorescence imaging processing system that measures/stores over 50 million pixels worth of data at two different magnifications. Artificial Intelligence algorithms within the nCyte-AI platform select entities of interest within an image capture area and displays multi-channel images of targets for clinician verification. We present here a comparative analysis of the performance of the point-of-care test in a side-by-side comparison to that of the physician in the clinic to verify the utility of this new test and validate its performance relative to the in-clinic diagnosis by the physician. Our goal is to complete the testing and validation phase to move toward FDA approval. Extension of this test to include sexually transmitted infections is also underway. Breast cancer is one of the most commonly diagnosed cancers with a very high mortality rate. Tamoxifen was the first selective estrogen receptor modulators (SERM) adapted for use on ER+ tumors. It is now joined by two additional SERMs (toremifene, and raloxifene) and one selective estrogen receptor downregulator (fulvestrant) as treatment options. Various enzymes have been shown to metabolize these drugs into active and inactive compounds, influence their transport out of the tumor or the body, and influence the types and intensity of side effects. Human variation in these enzymes may affect efficacy, adverse effects, and provide opportunities for drug interactions that could complicate treatment. A literature review was conducted using PubMed and Google Scholar to investigate the metabolism and common side effects of the drugs tamoxifen, toremifene, raloxifene, and fulvestrant. A table was assembled of all enzymes involved in maintaining therapeutic concentrations of these agents and all human variants that might alter this activity were identified. It is currently recognized that tamoxifen is primarily metabolized into an active metabolite by CYP3A4/3A5 and CYP2D6, with contributions from several other CYP enzymes. Enzymes from the SULT, FMO and UGT families mark it for excretion. Toremifene, Raloxifene, and Fulvestrant are active in their administered form and therefore have fewer enzymes that could influence activity. Tamoxifen has an extensive side effect profile and, because of the CYP enzymes involved in its metabolism, great potential for drug interactions, while newer agents show fewer potential complications. There is more work required to understand how genetics influences the efficacy and side effects of the newer agents in this class. The current work illustrates that a full pharmacokinetic pathway analysis of these agents is warranted and suggest that pharmacogenetic testing of an individual may allow for a more personalized and effective treatment approach. Using Pharmacogenetics to Personalize Hormone Therapy in the Treatment of Breast Cancer Presenter: James Mahaney, PhD Co-Authors: Carrie Champine, DO; Lisa Carroll, MD; Lindsey Call, DO; Peggy Robinson, John Kearney, Joe Bos, Yongjian Yu, Kent Murphy,Phd

*VCOM Student

Abstracts

Severe Orthopedic Trauma, Suspected Drug Abuse, and Homelessness: A Forensic Death Investigation Highlights a Need for Better Support for Vulnerable Populations in Southern Alabama Presenter: Melinda Carter, PhD Co-Authors: Taylor Bush*; Drama Cumbie*; Palmer Ford*; John Sisson*; Edward A. Reedy,MD, PhD Decomposed human remains recovered from southern Alabama were transported to the Montgomery Medical Examiners’ Office for autopsy during summer, 2022. The advanced stage of decay required removal of soft tissue and examination by both a forensic pathologist (E.R.) and anthropologist (M.C.). Standard osteological analysis of the person’s biological profile determined that these were the remains of a young adult male of European ancestry (“white”). Examination of the skeletal remains identified numerous poorly healed fractures throughout the skeleton, including an orthopedic plate on the right proximal humerus. Extremely poor dental health in a relatively young individual strongly suggests chronic drug use, though preliminary toxicological analysis of the soft tissue was negative. The remains were positively identified by comparison of medical records provided for a missing person in the area with the postmortem examination of the remains. The goal of this presentation is to address how a single traumatic incident required orthopedic surgical intervention, yet the patient’s lifestyle contributed to poor healing, infection that required another surgery, and ultimately homelessness and an unattended death, the cause and manner of which are undetermined. We address signs and symptoms of poor oral health that herald a patient in any clinical setting who may need additional attention and social support. We examine how chronic drug use can affect skeletal health and post operative healing. We discuss how certain vulnerable populations can obtain mental health support, food, and nutritional counseling. We also consider how manipulative medicine by osteopathic physicians might play a critical role in helping vulnerable patients. We present the science and complexity of this unfortunate patient outcome to shine a light on how death investigation can contribute to an awareness among healthcare workers of how mind, body, and spirit impact systemic health to stimulate discussions of how to better serve such people in need. Presenter: Blaise Costa, PhD Co-Authors: Seth Boehringer; Patrick Rafael BS; Tullia Johnston BS, MPH; Alyssa Ingram BS; Nakia Philip BS; Pamela VandeVord, PhD The normal function of N-methyl D-aspartate receptors (NMDARs) plays a critical role in brain development and cognitive function. Children born with mutations in NMDAR subunits, that reduce glutamate potency, suffer from various neuropsychiatric disorders including epilepsy, major depression, developmental delay, and intellectual disability. In the current work, to validate the capability of CNS4, - a novel agonist concentration-dependent NMDAR modulator, to preferentially potentiate hypoactive receptors, two disease-causing GluN2A mutants that are known to reduce glutamate potency to 4.4 (A548T) and 126 (V685G) fold were generated, sequenced and assayed using two-electrode voltage clamp electrophysiology technique. The results obtained from this experiment indicate that CNS4 significantly increased glutamate potency in A548T [(Glu EC50 in µM; 4.68 ±0.7, n=11 vs 1.93 ±0.55, n=5, p<0.05) and V685G (91.67 ±25.35, n=18 vs 0.99 ±0.14, n=17, p<0.01)] mutant expressing 2A receptors when co-expressed with wild type GluN1. However, CNS4 did not alter glutamate potency [(Glu EC50 in µM): 1.89 ±0.11, n=12 vs 2.58 ±0.45, n=5, p>0.05] in the wild-type GluN1/2A receptors. These results reveal that the CNS4 selectively modulates the hypoactive NMDARs. Previous findings demonstrated that CNS4 potentiated NMDA receptor currents disproportionately higher levels when activated by sub-saturating concentration of glutamate. Therefore, we hypothesize that CNS4 or its analogs will be an appropriate lead candidate for the development of clinically useful compounds to treat drug-resistant neuropsychiatric disorders like anti-NMDA receptor encephalitis. CNS4 preferentially potentiates hypoglutamatergic disease-causing mutant GluN1/2A subtype of NMDA receptors

*VCOM Student

Abstracts

Increased IL-6, but not TNF-α Release, In Response to Post Alcohol Consumption Occurs in Binge Drinkers But Not Social Drinkers Presenter: Darren Beck, PhD Co-Authors: Sara K. Blaine, PhD; Clayton M. Ridner; Benjamin R. Campbell; Eric D. Claus, PhD; Juliet R. Wilson*; Summer N. West*; Austin J. McClanahan*; Anna S. Siddiq*; Isaak M.P. Layman*; Emily B. Ansell, PhD; Jennifer L Robinson, PhD Objective and Design: Preclinical and clinical studies suggest learned neuroimmune system responses to alcohol cues and consumption may contribute to alcohol’s pharmacodynamic properties and/or Alcohol Use Disorder (AUD) pathogenesis. Mechanistically, these neuroimmune alterations may be associated with increased craving during alcohol consumption both acutely and over time. We sought to characterize this relationship in a randomized, counter-balanced, crossover experiment. Methods: Thirty-three binge drinkers (BD) and 31 non-binge, social drinkers (SD), matched for demographic and psychological variables, were exposed to alcohol cues and water cues. Each exposure was followed by the Alcohol Taste Test (ATT) of implicit motivation for alcohol to examine acute effects of cues, and a post-experiment one-month prospective measurement of their “real world” drinking behavior to approximate chronic effects. Blood plasma and craving measures were collected repeatedly to examine the effects of alcohol cues and alcohol consumption on Tumor necrosis factor alpha (TNF-α) and Interleukin 6 (IL-6) levels. Results: BD demonstrated significantly higher craving when compared to SD in response to alcohol cues, while group differences in IL-6 cue responses were not significant. Greater ATT consumption in BD was positively associated with alcohol cue-induced craving and IL-6 release post alcohol consumption. Additionally, craving post alcohol consumption and IL-6 release in response to alcohol consumption were each independently related to the number of drinks consumed in the next month for BD. TNF-α release to alcohol cues and consumption was not related to craving, IL-6 levels, immediate alcohol consumption, or future alcohol consumption. Conclusions: BD show greater alcohol craving and IL-6 release to acute alcohol consumption when compared to SD. Trial registration: Clinical Trials NCT04412824. Funding: National Institutes of Health grant R00-AA025401(SKB). Rationale: Pneumonia is a leading cause of acute respiratory distress syndrome and sepsis. Despite the resolution of active infection, pro-inflammatory mediators and cytotoxins elicited during the acute phase promote secondary tissue injury, impede recovery, and contribute to poor patient prognoses. Acute lung infection with Pseudomonas aeruginosa, Klebsiella pneumoniae, and influenza elicit pathogenic lung amyloids that propagate injury and likely contribute to the inflammatory milieu. However, clinical trials targeting amyloid-beta (Aβ) have consistently failed. Lung endothelial-derived amyloids have been implicated as innate antimicrobials yet the contribution of Aβ to the defense of the air-blood barrier remains poorly resolved. Here, we tested whether lung endothelial Aβ contributes to 1) the attenuation of active infection, and 2) endothelial barrier resilience to infection. Methods: CRISPR/Cas9 was targeted to Aβ precursor protein (APP) in rat pulmonary microvascular endothelial cells (PMVECs), and the deletion was confirmed via PCR, sequencing, and immunoblotting. The contribution of APP expression to cell proliferation, self-replication, wound closure, angiogenesis, and barrier integrity both at baseline and during virulent infection was assessed in WT, guide RNA control, and APP-/- PMVECs. Amyloid content was monitored with immunoblotting and Thioflavin T staining. Antimicrobicity was measured via kinetic bactericidal assays, agglutination, and plating. Results: APP-/- cells were ~49% less effective in reducing the bacterial load of active infection as compared to APP expressing PMVECs. Immunodepletion of Aβ from cell supernatant comparably reduced bactericidal efficacy. APP-/- cells also exhibited markedly impaired proliferation and replication capacity, and little resilience to infection with loss of barrier integrity in roughly half the time of control cells. Conclusions: Lung endothelial APP is an important contributor to host defense. APP and its Aβ variant(s) appear to constrain infective bacterial burden whereas APP products appear to function as mitogens/morphogens within the microvascular milieu, likely contributing to tissue repair and recovery post-insult. Amyloid-Beta Precursor Protein: Essential to Lung Capillary Barrier Defense During Acute Infection Presenter: Sarah Voth, PhD Co-Authors: Chung-Sik Choi, PhD; Rebekah Morrow, PhD; Meredith Gwin, BS; Mike Lin, PhD; Samir Gautam, MD, PhD; Dara W. Frank, PhD; Jonathan P. Audia, PhD; Troy Stevens, Phd; Lokesh Sharma,Phd; Charles Dela Cruz, MD, PhD; K. Adam Morrow, PhD

*VCOM Student