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Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar May 2024

Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar

Theses & Dissertations

Group 3 medulloblastoma (MB) has the worst prognosis of the MB subgroups associated with elevated MYC expression and a 5-year survival rate of

Quantitation of EPZ was performed on a Shimadzu LC-MS/MS system utilizing electrospray ionization operated in positive mode. The validated assay was linear from 0.2 to 500 ng/mL. Metabolic stability studies demonstrated slow intrinsic clearance of EPZ in mouse and human liver microsomes, suggesting no CYP-mediated metabolism. Additionally, EPZ exhibited low binding affinity to plasma and brain proteins and high apparent permeability across artificial membranes, indicating efficient membrane penetration. Drug transporter studies identified EPZ as a substrate of …


The Tensegrity Curriculum: A Comprehensive Curricular Structure Supporting Cultural Humility In Undergraduate Medical Education., Anne C Jones, Kristin N Bertsch, Deborah Williams, Millicent King Channell May 2024

The Tensegrity Curriculum: A Comprehensive Curricular Structure Supporting Cultural Humility In Undergraduate Medical Education., Anne C Jones, Kristin N Bertsch, Deborah Williams, Millicent King Channell

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Due to growing health disparities in underserved communities, a comprehensive approach is needed to train physicians to work effectively with patients who have cultures and belief systems different from their own. To address these complex healthcare inequities, Rowan-Virtua SOM implemented a new curriculum, The Tensegrity Curriculum, designed to expand beyond just teaching skills of cultural competence to include trainees' exploration of cultural humility. The hypothesis is that this component of the curriculum will mitigate health inequity by training physicians to recognize and interrupt the bias within themselves and within systems. Early outcomes of this curricular renewal process reveal increased student …


Sages Guidelines For The Use Of Laparoscopy During Pregnancy, Sunjay S. Kumar, Amelia T. Collings, Claire Wunker, Dimitrios I. Athanasiadis, Colin G. Delong, Julie S. Hong, Mohammed T. Ansari, Ahmed Abou-Setta, Emily Oliver, Vincenzo Berghella, Vamsi Alli, Imran Hassan, Celeste Hollands, Patricia Sylla, Bethany J. Slater, Francesco Palazzo May 2024

Sages Guidelines For The Use Of Laparoscopy During Pregnancy, Sunjay S. Kumar, Amelia T. Collings, Claire Wunker, Dimitrios I. Athanasiadis, Colin G. Delong, Julie S. Hong, Mohammed T. Ansari, Ahmed Abou-Setta, Emily Oliver, Vincenzo Berghella, Vamsi Alli, Imran Hassan, Celeste Hollands, Patricia Sylla, Bethany J. Slater, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: When pregnant patients present with nonobstetric pathology, the physicians caring for them may be uncertain about the optimal management strategy. The aim of this guideline is to develop evidence-based recommendations for pregnant patients presenting with common surgical pathologies including appendicitis, biliary disease, and inflammatory bowel disease (IBD).

METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee convened a working group to address these issues. The group generated five key questions and completed a systematic review and meta-analysis of the literature. An expert panel then met to form evidence-based recommendations according to the Grading of Recommendations Assessment, …


Focal Adhesion Kinase-Yap Signaling Axis Drives Drug-Tolerant Persister Cells And Residual Disease In Lung Cancer, Franziska Haderk, Yu-Ting Chou, Lauren Cech, Celia Fernández-Méndez, Johnny Yu, Victor Olivas, Ismail M Meraz, Dora Barbosa Rabago, D Lucas Kerr, Carlos Gomez, David V Allegakoen, Juan Guan, Khyati N Shah, Kari A Herrington, Oghenekevwe M Gbenedio, Shigeki Nanjo, Mourad Majidi, Whitney Tamaki, Yashar K Pourmoghadam, Julia K Rotow, Caroline E Mccoach, Jonathan W Riess, J Silvio Gutkind, Tracy T Tang, Leonard Post, Bo Huang, Pilar Santisteban, Hani Goodarzi, Sourav Bandyopadhyay, Calvin J Kuo, Jeroen P Roose, Wei Wu, Collin M Blakely, Jack A Roth, Trever G Bivona May 2024

Focal Adhesion Kinase-Yap Signaling Axis Drives Drug-Tolerant Persister Cells And Residual Disease In Lung Cancer, Franziska Haderk, Yu-Ting Chou, Lauren Cech, Celia Fernández-Méndez, Johnny Yu, Victor Olivas, Ismail M Meraz, Dora Barbosa Rabago, D Lucas Kerr, Carlos Gomez, David V Allegakoen, Juan Guan, Khyati N Shah, Kari A Herrington, Oghenekevwe M Gbenedio, Shigeki Nanjo, Mourad Majidi, Whitney Tamaki, Yashar K Pourmoghadam, Julia K Rotow, Caroline E Mccoach, Jonathan W Riess, J Silvio Gutkind, Tracy T Tang, Leonard Post, Bo Huang, Pilar Santisteban, Hani Goodarzi, Sourav Bandyopadhyay, Calvin J Kuo, Jeroen P Roose, Wei Wu, Collin M Blakely, Jack A Roth, Trever G Bivona

Faculty, Staff and Student Publications

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling …


Triggering Receptor Expressed On Myeloid Cells 2 (Trem2) Regulates Phagocytosis In Glioblastoma, Mekenzie M Peshoff, Pravesh Gupta, Shivangi Oberai, Rakesh Trivedi, Hiroshi Katayama, Prashanth Chakrapani, Minghao Dang, Simona Migliozzi, Joy Gumin, Divya B Kadri, Jessica K Lin, Nancy K Milam, Mark E Maynard, Brian D Vaillant, Brittany Parker-Kerrigan, Frederick F Lang, Jason T Huse, Antonio Iavarone, Linghua Wang, Karen Clise-Dwyer, Krishna P Bhat May 2024

Triggering Receptor Expressed On Myeloid Cells 2 (Trem2) Regulates Phagocytosis In Glioblastoma, Mekenzie M Peshoff, Pravesh Gupta, Shivangi Oberai, Rakesh Trivedi, Hiroshi Katayama, Prashanth Chakrapani, Minghao Dang, Simona Migliozzi, Joy Gumin, Divya B Kadri, Jessica K Lin, Nancy K Milam, Mark E Maynard, Brian D Vaillant, Brittany Parker-Kerrigan, Frederick F Lang, Jason T Huse, Antonio Iavarone, Linghua Wang, Karen Clise-Dwyer, Krishna P Bhat

Faculty, Staff and Student Publications

Background: Glioblastomas (GBMs) are central nervous system tumors that resist standard-of-care interventions and even immune checkpoint blockade. Myeloid cells in the tumor microenvironment can contribute to GBM progression; therefore, emerging immunotherapeutic approaches include reprogramming these cells to achieve desirable antitumor activity. Triggering receptor expressed on myeloid cells 2 (TREM2) is a myeloid signaling regulator that has been implicated in a variety of cancers and neurological diseases with contrasting functions, but its role in GBM immunopathology and progression is still under investigation.

Methods: Our reverse translational investigations leveraged single-cell RNA sequencing and cytometry of human gliomas to characterize TREM2 expression across …


Autologous Bone Marrow Mononuclear Cells To Treat Severe Traumatic Brain Injury In Children, Charles S Cox, David M Notrica, Jenifer Juranek, Jeffrey H Miller, Fabio Triolo, Steven Kosmach, Sean I Savitz, P David Adelson, Claudia Pedroza, Scott D Olson, Michael C Scott, Akshita Kumar, Benjamin M Aertker, Henry W Caplan, Margaret L Jackson, Brijesh S Gill, Robert A Hetz, Michael S Lavoie, Linda Ewing-Cobbs May 2024

Autologous Bone Marrow Mononuclear Cells To Treat Severe Traumatic Brain Injury In Children, Charles S Cox, David M Notrica, Jenifer Juranek, Jeffrey H Miller, Fabio Triolo, Steven Kosmach, Sean I Savitz, P David Adelson, Claudia Pedroza, Scott D Olson, Michael C Scott, Akshita Kumar, Benjamin M Aertker, Henry W Caplan, Margaret L Jackson, Brijesh S Gill, Robert A Hetz, Michael S Lavoie, Linda Ewing-Cobbs

Faculty, Staff and Student Publications

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood–brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes.

We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5–17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were …


Gain-Of-Function And Loss-Of-Function Variants In Gria3 Lead To Distinct Neurodevelopmental Phenotypes, Berardo Rinaldi, Allan Bayat, Linda G Zachariassen, Jia-Hui Sun, Yu-Han Ge, Dan Zhao, Kristine Bonde, Laura H Madsen, Ilham Abdimunim Ali Awad, Duygu Bagiran, Amal Sbeih, Syeda Maidah Shah, Shaymaa El-Sayed, Signe M Lyngby, Miriam G Pedersen, Charlotte Stenum-Berg, Louise Claudia Walker, Ilona Krey, Andrée Delahaye-Duriez, Lisa T Emrick, Krystal Sully, Chaya N Murali, Lindsay C Burrage, Julie Ana Plaud Gonzalez, Mered Parnes, Jennifer Friedman, Bertrand Isidor, Jérémie Lefranc, Sylvia Redon, Delphine Heron, Cyril Mignot, Boris Keren, Mélanie Fradin, Christele Dubourg, Sandra Mercier, Thomas Besnard, Benjamin Cogne, Wallid Deb, Clotilde Rivier, Donatella Milani, Maria Francesca Bedeschi, Claudia Di Napoli, Federico Grilli, Paola Marchisio, Suzanna Koudijs, Danielle Veenma, Emanuela Argilli, Sally Ann Lynch, Ping Yee Billie Au, Fernando Eduardo Ayala Valenzuela, Carolyn Brown, Diane Masser-Frye, Marilyn Jones, Leslie Patron Romero, Wenhui Laura Li, Erin Thorpe, Laura Hecher, Jessika Johannsen, Jonas Denecke, Vanda Mcniven, Anna Szuto, Emma Wakeling, Vincent Cruz, Valerie Sency, Heng Wang, Juliette Piard, Fanny Kortüm, Theresia Herget, Tatjana Bierhals, Angelo Condell, Bruria Ben-Zeev, Simranpreet Kaur, John Christodoulou, Amelie Piton, Christiane Zweier, Cornelia Kraus, Alessia Micalizzi, Marina Trivisano, Nicola Specchio, Gaetan Lesca, Rikke S Møller, Zeynep Tümer, Maria Musgaard, Benedicte Gerard, Johannes R Lemke, Yun Stone Shi, Anders S Kristensen May 2024

Gain-Of-Function And Loss-Of-Function Variants In Gria3 Lead To Distinct Neurodevelopmental Phenotypes, Berardo Rinaldi, Allan Bayat, Linda G Zachariassen, Jia-Hui Sun, Yu-Han Ge, Dan Zhao, Kristine Bonde, Laura H Madsen, Ilham Abdimunim Ali Awad, Duygu Bagiran, Amal Sbeih, Syeda Maidah Shah, Shaymaa El-Sayed, Signe M Lyngby, Miriam G Pedersen, Charlotte Stenum-Berg, Louise Claudia Walker, Ilona Krey, Andrée Delahaye-Duriez, Lisa T Emrick, Krystal Sully, Chaya N Murali, Lindsay C Burrage, Julie Ana Plaud Gonzalez, Mered Parnes, Jennifer Friedman, Bertrand Isidor, Jérémie Lefranc, Sylvia Redon, Delphine Heron, Cyril Mignot, Boris Keren, Mélanie Fradin, Christele Dubourg, Sandra Mercier, Thomas Besnard, Benjamin Cogne, Wallid Deb, Clotilde Rivier, Donatella Milani, Maria Francesca Bedeschi, Claudia Di Napoli, Federico Grilli, Paola Marchisio, Suzanna Koudijs, Danielle Veenma, Emanuela Argilli, Sally Ann Lynch, Ping Yee Billie Au, Fernando Eduardo Ayala Valenzuela, Carolyn Brown, Diane Masser-Frye, Marilyn Jones, Leslie Patron Romero, Wenhui Laura Li, Erin Thorpe, Laura Hecher, Jessika Johannsen, Jonas Denecke, Vanda Mcniven, Anna Szuto, Emma Wakeling, Vincent Cruz, Valerie Sency, Heng Wang, Juliette Piard, Fanny Kortüm, Theresia Herget, Tatjana Bierhals, Angelo Condell, Bruria Ben-Zeev, Simranpreet Kaur, John Christodoulou, Amelie Piton, Christiane Zweier, Cornelia Kraus, Alessia Micalizzi, Marina Trivisano, Nicola Specchio, Gaetan Lesca, Rikke S Møller, Zeynep Tümer, Maria Musgaard, Benedicte Gerard, Johannes R Lemke, Yun Stone Shi, Anders S Kristensen

Faculty, Staff and Students Publications

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1–GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally.

Here, we evaluated the impact on AMPAR function of one frameshift and 43 rare missense GRIA3 variants identified in patients with NDD by electrophysiological assays. Thirty-one variants alter receptor function and show loss-of-function or gain-of-function properties, whereas 13 appeared neutral.

We collected detailed …


Risk Of Meningomyelocele Mediated By The Common 22q112 Deletion, Keng Ioi Vong, Sangmoon Lee, Kit Sing Au, T Blaine Crowley, Valeria Capra, Jeremiah Martino, Meade Haller, Camila Araújo, Hélio R Machado, Renee George, Bryn Gerding, Kiely N James, Valentina Stanley, Nan Jiang, Kameron Alu, Naomi Meave, Anna S Nidhiry, Fiza Jiwani, Isaac Tang, Ashna Nisal, Ishani Jhamb, Arzoo Patel, Aakash Patel, Jennifer Mcevoy-Venneri, Chelsea Barrows, Celina Shen, Yoo-Jin Ha, Robyn Howarth, Madison Strain, Allison Elizabeth Ashley-Koch, Matloob Azam, Sara Mumtaz, Gyang Markus Bot, Richard H Finnell, Zoha Kibar, Ahmed I Marwan, Gia Melikishvili, Hal S Meltzer, Osvaldo M Mutchinick, David A Stevenson, Henry J Mroczkowski, Betsy Ostrander, Erica Schindewolf, Julie Moldenhauer, Elaine H Zackai, Beverly S Emanuel, Sixto Garcia-Minaur, Beata A Nowakowska, Roger E Stevenson, Maha S Zaki, Hope Northrup, Hanna K Mcnamara, Kimberly A Aldinger, Ian G Phelps, Mei Deng, Ian A Glass, Bernice Morrow, Donna M Mcdonald-Mcginn, Simone Sanna-Cherchi, Dolores J Lamb, Joseph G Gleeson May 2024

Risk Of Meningomyelocele Mediated By The Common 22q112 Deletion, Keng Ioi Vong, Sangmoon Lee, Kit Sing Au, T Blaine Crowley, Valeria Capra, Jeremiah Martino, Meade Haller, Camila Araújo, Hélio R Machado, Renee George, Bryn Gerding, Kiely N James, Valentina Stanley, Nan Jiang, Kameron Alu, Naomi Meave, Anna S Nidhiry, Fiza Jiwani, Isaac Tang, Ashna Nisal, Ishani Jhamb, Arzoo Patel, Aakash Patel, Jennifer Mcevoy-Venneri, Chelsea Barrows, Celina Shen, Yoo-Jin Ha, Robyn Howarth, Madison Strain, Allison Elizabeth Ashley-Koch, Matloob Azam, Sara Mumtaz, Gyang Markus Bot, Richard H Finnell, Zoha Kibar, Ahmed I Marwan, Gia Melikishvili, Hal S Meltzer, Osvaldo M Mutchinick, David A Stevenson, Henry J Mroczkowski, Betsy Ostrander, Erica Schindewolf, Julie Moldenhauer, Elaine H Zackai, Beverly S Emanuel, Sixto Garcia-Minaur, Beata A Nowakowska, Roger E Stevenson, Maha S Zaki, Hope Northrup, Hanna K Mcnamara, Kimberly A Aldinger, Ian G Phelps, Mei Deng, Ian A Glass, Bernice Morrow, Donna M Mcdonald-Mcginn, Simone Sanna-Cherchi, Dolores J Lamb, Joseph G Gleeson

Faculty, Staff and Student Publications

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of


Cancer Stem Cell Hypothesis 2.0 In Glioblastoma: Where Are We Now And Where Are We Going?, Anthony R Sloan, Daniel J Silver, Sam Kint, Marco Gallo, Justin D Lathia May 2024

Cancer Stem Cell Hypothesis 2.0 In Glioblastoma: Where Are We Now And Where Are We Going?, Anthony R Sloan, Daniel J Silver, Sam Kint, Marco Gallo, Justin D Lathia

Faculty, Staff and Students Publications

Over the past 2 decades, the cancer stem cell (CSC) hypothesis has provided insight into many malignant tumors, including glioblastoma (GBM). Cancer stem cells have been identified in patient-derived tumors and in some mouse models, allowing for a deeper understanding of cellular and molecular mechanisms underlying GBM growth and therapeutic resistance. The CSC hypothesis has been the cornerstone of cellular heterogeneity, providing a conceptual and technical framework to explain this longstanding phenotype in GBM. This hypothesis has evolved to fit recent insights into how cellular plasticity drives tumor growth to suggest that CSCs do not represent a distinct population but …


Interactions Between Repetitive Mild Traumatic Brain Injury And Methylphenidate Administration On Catecholamine Transporter Protein Levels Within The Rodent Prefrontal Cortex, Anna Abrimian, Eleni Papadopoulos, Christopher P. Knapp, J. Loweth, Barry Waterhouse, Rachel Navarra May 2024

Interactions Between Repetitive Mild Traumatic Brain Injury And Methylphenidate Administration On Catecholamine Transporter Protein Levels Within The Rodent Prefrontal Cortex, Anna Abrimian, Eleni Papadopoulos, Christopher P. Knapp, J. Loweth, Barry Waterhouse, Rachel Navarra

Rowan-Virtua Research Day

It is theorized that low concentrations of dopamine (DA) and norepinephrine (NE) within in the prefrontal cortex (PFC) following traumatic brain injury (TBI) leads to increased risky behavior. Our lab has shown that repeated mild TBI (rmTBI) sex-differentially increases risky behavior in a rodent model. Methylphenidate (MPH) is a psychostimulant drug used to treat symptoms of Attention-Deficit Hyperactivity Disorder (ADHD), also driven by a hypo-catecholaminergic PFC. MPH elevates catecholamine levels by blocking DA and NE transporters, DAT and NET. While the potential of psychostimulants to treat post-TBI symptoms have been explored, the effects of sub-chronic MPH on transporter levels following …


Can Nutritional Supplements Benefit Patients Receiving Treatment For Neurodegenerative Disorders?, Russell Levi, Saad Ahmed, Zachary Harris May 2024

Can Nutritional Supplements Benefit Patients Receiving Treatment For Neurodegenerative Disorders?, Russell Levi, Saad Ahmed, Zachary Harris

Rowan-Virtua Research Day

As the prevalence of neurocognitive disorders rises globally, developing new methodologies of prevention and treatment is crucial. This literature review examines the efficacy of adding nutritional supplements, specifically nootropics, with traditional pharmacological regimens on various neurocognitive and neurodegenerative disorders. Primary, peer-reviewed research, including both human and animal studies, was assesed to determine if there was a benefifical, minimal, or detrimental effect on symptom progression. The inclusion criteria focused on studies that evaluated the reduction in disease markers or symptoms following supplement use. The findings reveal that natural supplements generally support disease management. Significant improvements were noted with specific combinations like …


Case Report: Monkeypox Diagnosed In The Ed, Richard M. Baluyot, Joseph Pagano, James A. Espinosa, Alan Lucerna May 2024

Case Report: Monkeypox Diagnosed In The Ed, Richard M. Baluyot, Joseph Pagano, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Rashes are one of the most common chief complaints we see as emergency medicine physicians on a day-to-day basis. Most of them tend to be self-limited and require very little workup and can be discharged home; however, it is our job to try to identify rashes that may require isolation in order to prevent an outbreak in our communities. Here we present a case of one such rash that has gained major media attention as of late, Monkeypox.


Clostridium Perfringens Sepsis From A Hepatic Abscess With Hemolysis And Renal Failure, Requiring Hemodialysis, Joel Collins Ii, Katelyn Courtney, James A. Espinosa, Alan Lucerna May 2024

Clostridium Perfringens Sepsis From A Hepatic Abscess With Hemolysis And Renal Failure, Requiring Hemodialysis, Joel Collins Ii, Katelyn Courtney, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

The prognosis of sepsis caused by Clostridium perfringens is extremely poor, with a mortality rate of 70%-100%. Management includes antibiotic regimens specific to toxin production as well as source control via surgical or interventional mechanisms. We report a case of a 64-year-old male who presented with right upper quadrant (RUQ) abdominal pain and was diagnosed with Clostridium perfringens bacteremia with associated acalculous cholecystitis, hepatic abscess, and acute renal failure requiring hemodialysis. It is felt that early hemodialysis was an associated factor in the patient's survival.


Preventing Postoperative Cognitive Dysfunction Through Preoperative Exercise, John Andre Socci May 2024

Preventing Postoperative Cognitive Dysfunction Through Preoperative Exercise, John Andre Socci

Rowan-Virtua Research Day

Introduction: Postoperative cognitive dysfunction (POCD) is a common problem in the elderly population after undergoing anesthesia that results in sometimes irreversible cognitive and physical impairment that can increase mortality and decrease quality of life.

Methods: To see the relationship between preoperative fitness capacity and how this relates to postoperative cognitive ability a literature review was performed. Studies that were included involved populations older than sixty years old that had undergone anesthesia. Additionally, animal studies were included to show inflammatory marker levels and how they increased in relation to physical activity.

Results: Various fitness scales were used such as the Timed …


A Preliminary Report On The Role Of Lipoxin A4 In Reinstating The Blood-Brain Barrier Integrity In A Rodent Model Of Acute Inflammation With Impaired Cerebrovasculature, Minjal Patel, Shruti Varshney, Ananya Nethikunta, George G. Godsey, Mary C. Kosciuk, Ana Rodriguez, Bernd Spur, Kingsley Yin, Randel L. Swanson, Venkat Venkataraman, Robert G. Nagele, Nimish Acharya May 2024

A Preliminary Report On The Role Of Lipoxin A4 In Reinstating The Blood-Brain Barrier Integrity In A Rodent Model Of Acute Inflammation With Impaired Cerebrovasculature, Minjal Patel, Shruti Varshney, Ananya Nethikunta, George G. Godsey, Mary C. Kosciuk, Ana Rodriguez, Bernd Spur, Kingsley Yin, Randel L. Swanson, Venkat Venkataraman, Robert G. Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: The blood-brain barrier (BBB) is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI). Lipoxins (LXs) are a class of arachidonate-derived eicosanoids, which are a class of specialized pro-resolving lipid mediators (SPMs). SPMs are known to inhibit immune response through inhibition of cellular infiltration, downregulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Hence, LXs are recognized as “breaking signals” in the inflammatory process. One form of LXs, Lipoxin A4 (LXA4) …


Efficacy Of Psilocybin In The Treatment Of Substance And Alcohol Use Disorders, Hanna Brancaccio May 2024

Efficacy Of Psilocybin In The Treatment Of Substance And Alcohol Use Disorders, Hanna Brancaccio

Rowan-Virtua Research Day

Introduction: Substance use disorder (SUD) and alcohol use disorder (AUD) are major public health crises, affecting millions of Americans. Current treatment options include behavioral therapies and medications. In this review, we explored psilocybin’s efficacy in treating SUD and AUD.

Methods: Key terms were used to search databases to identify articles that addressed psilocybin in the treatment of SUD. Included in the review were indexed, peer-reviewed, primary sources that were published within the last 10 years. Excluded studies were non-peer reviewed, not relevant to the thesis, and did not have an English translation.

Results: The psychodynamic antidepressant effects of psilocybin mark …


The Impact Of Traumatic Brain Injury On Noradrenergic Innervation Of The Prefrontal Cortex, Jil P. Modi, Christopher P. Knapp, Rachel L. Navarra May 2024

The Impact Of Traumatic Brain Injury On Noradrenergic Innervation Of The Prefrontal Cortex, Jil P. Modi, Christopher P. Knapp, Rachel L. Navarra

Rowan-Virtua Research Day

Traumatic Brain Injury (TBI) is a common cause of death and disability in the United States, and it can occur due to varied reasons including motor vehicle accidents, gunshot wounds, and falls. Following TBIs, patients are often left with lifelong disabilities and cognitive problems that can lead to increased risk-taking behaviors. The main goal of my research was to understand the neural mechanisms that drive increased risk-taking behaviors due to TBIs. The specific areas of the brain I was interested in looking at were the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), and/or anterior cingulate cortex (ACC) of the prefrontal …


Ketamine Crisis: Case Report On The Complications Of Ketamine Usage And Its Rise In The United States, Shika Veera, Vajreshwari Shivaprakash May 2024

Ketamine Crisis: Case Report On The Complications Of Ketamine Usage And Its Rise In The United States, Shika Veera, Vajreshwari Shivaprakash

Rowan-Virtua Research Day

The recreational use of ketamine poses various health risks, including addiction, cognitive impairments, and physical harm.

The patient is a 24-year-old female who presented with 30 lbs. unintentional weight loss, generalized weakness, and urinary incontinence over four months. She endorses right upper quadrant and suprapubic pain with occasional gross hematuria. The patient denied recreational drug use. Urine drug screen was negative. Gynecologic exam and STI testing were without concerns. On exam, she had positive right lower quadrant tenderness, suprapubic tenderness, and costovertebral angle tenderness bilaterally. The patient was admitted to the ICU due to weakness and significant hyponatremia at 115. …


Health Benefits Of Saccharomyces Boulardii As A Probiotic, Devashri Parikh, Maftuna Kurbonnazarova, Ravij Upadhyay, Andrea Iannuzzelli May 2024

Health Benefits Of Saccharomyces Boulardii As A Probiotic, Devashri Parikh, Maftuna Kurbonnazarova, Ravij Upadhyay, Andrea Iannuzzelli

Rowan-Virtua Research Day

Saccharomyces boulardii (SB), a budding yeast, within the Saccharomyces genus. It commonly used as a probiotic that has been isolated from lychee and mangosteen fruit. S. boulardii is not known to acquire resistant genes and does not last in the intestine after 3-5 days of discontinuing the ingestion. The clinical efficacy of this probiotic yeast is known to improve various diarrhea such as pediatric diarrhea, antibiotic-associated diarrhea, acute diarrhea, and traveler’s diarrhea. Additionally, when used as an adjuvant to treatment for Helicobacter pylori and Clostridium difficile infections, it improves bacterial eradication, prevents relapse, reduces adverse reactions and treatment-associated diarrhea.

Several …


Effect Of Dosage On Severity Of Dysphagia In A Toxicological Rat Model Of Parkinson's Disease, Shivam Patel, Taylor Good, Nicholas Zanghi, Francois Gould May 2024

Effect Of Dosage On Severity Of Dysphagia In A Toxicological Rat Model Of Parkinson's Disease, Shivam Patel, Taylor Good, Nicholas Zanghi, Francois Gould

Rowan-Virtua Research Day

Parkinson’s Disease (PD) is a prevalent and devastating neurodegenerative disorder that causes progressively worsening motor symptoms affecting locomotor and oropharyngeal function. There is limited research in animal models on swallowing dysfunction in PD. To examine how neurodegeneration in PD produces progressive impairment in the oropharyngeal and locomotor processes, rotenone, a type II mitochondrial inhibitor, was injected into Lewis rat models to reproduce a parkinsonian phenotype. We hypothesized that the animal models injected with the rotenone will exhibit both oropharyngeal dysfunction and locomotor deficiency with an increased deficit that correlates with prolonged treatment. We utilized 18 rats receiving either 2.75 mg/kg …


Serum Antibodies To Periodontal Pathogens And Anti-Malondialdehyde-Acetaldehyde: Potential Role In The Interrelationship Between The Periodontium And Rheumatoid Arthritis, Joyce Lee May 2024

Serum Antibodies To Periodontal Pathogens And Anti-Malondialdehyde-Acetaldehyde: Potential Role In The Interrelationship Between The Periodontium And Rheumatoid Arthritis, Joyce Lee

Theses & Dissertations

Objectives: Study 1 – To quantify associations between anti-Porphyromonas gingivalis, anti-Prevotella intermedia, and anti-Fusobacterium nucleatum serum antibody concentrations and risk of developing rheumatoid arthritis (RA). Study 2 – To test if periodontal clinical measures, alveolar bone loss (ABL), and the aforementioned serum anti-bacterial antibody concentrations are associated with anti-malondialdehyde-acetaldehyde (MAA) serum antibody concentrations.

Methods: Study 1 – Serum samples pre- and post- RA diagnosis (n=214 cases, 210 matched controls) from the U.S. Department of Defense Serum Repository were utilized to compare timing of elevations of anti-bacterial antibody concentrations relative to RA diagnosis and associations …


Fam86a Methylation Of Eef2 Links Mrna Translation Elongation To Tumorigenesis, Joel William Francis, Simone Hausmann, Sabeen Ikram, Kunlun Yin, Robert Mealey-Farr, Natasha Mahealani Flores, Annie Truc Trinh, Tourkian Chasan, Julia Thompson, Pawel Karol Mazur, Or Gozani May 2024

Fam86a Methylation Of Eef2 Links Mrna Translation Elongation To Tumorigenesis, Joel William Francis, Simone Hausmann, Sabeen Ikram, Kunlun Yin, Robert Mealey-Farr, Natasha Mahealani Flores, Annie Truc Trinh, Tourkian Chasan, Julia Thompson, Pawel Karol Mazur, Or Gozani

Faculty, Staff and Student Publications

eEF2 post-translational modifications (PTMs) can profoundly affect mRNA translation dynamics. However, the physiologic function of eEF2K525 trimethylation (eEF2K525me3), a PTM catalyzed by the enzyme FAM86A, is unknown. Here, we find that FAM86A methylation of eEF2 regulates nascent elongation to promote protein synthesis and lung adenocarcinoma (LUAD) pathogenesis. The principal physiologic substrate of FAM86A is eEF2, with K525me3 modeled to facilitate productive eEF2-ribosome engagement during translocation. FAM86A depletion in LUAD cells causes 80S monosome accumulation and mRNA translation inhibition. FAM86A is overexpressed in LUAD and eEF2K525me3 levels increase through advancing LUAD disease stages. FAM86A knockdown attenuates LUAD cell proliferation and suppression …


Mdm2 Inhibitors For Cancer Therapy: The Past, Present, And Future, Wei Wang, Najah Albadari, Yi Du, Josef F Fowler, Hannah T Sang, Wa Xian, Frank Mckeon, Wei Li, Jia Zhou, Ruiwen Zhang May 2024

Mdm2 Inhibitors For Cancer Therapy: The Past, Present, And Future, Wei Wang, Najah Albadari, Yi Du, Josef F Fowler, Hannah T Sang, Wa Xian, Frank Mckeon, Wei Li, Jia Zhou, Ruiwen Zhang

Faculty, Staff and Student Publications

Since its discovery over 35 years ago, MDM2 has emerged as an attractive target for the development of cancer therapy. MDM2's activities extend from carcinogenesis to immunity to the response to various cancer therapies. Since the report of the first MDM2 inhibitor more than 30 years ago, various approaches to inhibit MDM2 have been attempted, with hundreds of small-molecule inhibitors evaluated in preclinical studies and numerous molecules tested in clinical trials. Although many MDM2 inhibitors and degraders have been evaluated in clinical trials, there is currently no Food and Drug Administration (FDA)-approved MDM2 inhibitor on the market. Nevertheless, there are …


Community-Acquired Pneumonia: A Us Perspective On The Guideline Gap, Maricar Malinis, Lilian Abbo, Jose A Vazquez, Luis Ostrosky-Zeichner May 2024

Community-Acquired Pneumonia: A Us Perspective On The Guideline Gap, Maricar Malinis, Lilian Abbo, Jose A Vazquez, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.


De Novo Genome Assembly For The Coppery Titi Monkey (Plecturocebus Cupreus): An Emerging Nonhuman Primate Model For Behavioral Research, Susanne P Pfeifer, Alexander Baxter, Logan E Savidge, Fritz J Sedlazeck, Karen L Bales May 2024

De Novo Genome Assembly For The Coppery Titi Monkey (Plecturocebus Cupreus): An Emerging Nonhuman Primate Model For Behavioral Research, Susanne P Pfeifer, Alexander Baxter, Logan E Savidge, Fritz J Sedlazeck, Karen L Bales

Faculty, Staff and Students Publications

The coppery titi monkey (Plecturocebus cupreus) is an emerging nonhuman primate model system for behavioral and neurobiological research. At the same time, the almost entire absence of genomic resources for the species has hampered insights into the genetic underpinnings of the phenotypic traits of interest. To facilitate future genotype-to-phenotype studies, we here present a high-quality, fully annotated de novo genome assembly for the species with chromosome-length scaffolds spanning the autosomes and chromosome X (scaffold N50 = 130.8 Mb), constructed using data obtained from several orthologous short- and long-read sequencing and scaffolding techniques. With a base-level accuracy of ∼99.99% in chromosome-length …


Optimization, Characterization, And Comparison Of Two Luciferase-Expressing Mouse Glioblastoma Models, Louis Rodgers, Julia A. Schulz Pauly, Bryan J. Maloney, Anika M. S. Hartz, Bjoern Bauer May 2024

Optimization, Characterization, And Comparison Of Two Luciferase-Expressing Mouse Glioblastoma Models, Louis Rodgers, Julia A. Schulz Pauly, Bryan J. Maloney, Anika M. S. Hartz, Bjoern Bauer

UK CARES Faculty Publications

Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and the treatment response are typically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable. However, BLI requires luciferase-tagged cells, and recent studies indicate that the luciferase gene can elicit an immune response, leading to tumor rejection and experimental variation. We sought to optimize the engraftment of two luciferase-expressing GBM models, GL261 Red-FLuc and TRP-mCherry-FLuc, showing differences …


Proof-Of-Concept For Converging Beam Small Animal Irradiator, Benjamin Insley May 2024

Proof-Of-Concept For Converging Beam Small Animal Irradiator, Benjamin Insley

Dissertations and Theses (Open Access)

The Monte Carlo particle simulator TOPAS, the multiphysics solver COMSOL., and

several analytical radiation transport methods were employed to perform an in-depth proof-ofconcept

for a high dose rate, high precision converging beam small animal irradiation platform.

In the first aim of this work, a novel carbon nanotube-based compact X-ray tube optimized for

high output and high directionality was designed and characterized. In the second aim, an

optimization algorithm was developed to customize a collimator geometry for this unique Xray

source to simultaneously maximize the irradiator’s intensity and precision. Then, a full

converging beam irradiator apparatus was fit with a multitude …


Outcomes Of Primary Acl Repair For Proximal Tears: A Systematic Review And Meta Analysis, Collin Braithwaite, Tanner Hafen, Robert Dean, Joseph Guettler, James Bicos May 2024

Outcomes Of Primary Acl Repair For Proximal Tears: A Systematic Review And Meta Analysis, Collin Braithwaite, Tanner Hafen, Robert Dean, Joseph Guettler, James Bicos

Posters

The purpose of this study was to determine which primary ACL repair technique resulted in the lowest failure rates postoperatively.


Fatty Acid Concentrations In Preterm Infants Fed The Exclusive Human Milk Diet: A Prospective Cohort Study, Lindsay F Holzapfel, Jana P Unger, Pam Gordon, Heeju Yang, Joanne E Cluette-Brown, Laura A Gollins, Amy B Hair, Camilia R Martin May 2024

Fatty Acid Concentrations In Preterm Infants Fed The Exclusive Human Milk Diet: A Prospective Cohort Study, Lindsay F Holzapfel, Jana P Unger, Pam Gordon, Heeju Yang, Joanne E Cluette-Brown, Laura A Gollins, Amy B Hair, Camilia R Martin

Faculty, Staff and Student Publications

OBJECTIVE: Quantify blood fatty acids and growth outcomes in preterm infants fed the exclusive human milk diet.

METHODS: A prospective cohort study of 30 infants 24-34 weeks gestation and ≤1250 g fed the exclusive human milk diet. Blood fatty acids were quantified at two time points. Comparisons were made using two-sample t-tests and Wilcoxon rank sum.

RESULTS: Donor human milk-fed (n = 12) compared to mother's own milk-fed infants (n = 18) from birth to after 28 days of life, had an increased interval change of linoleic to docosahexaenoic acid ratio (5.5 vs. -1.1 mole percent ratio, p = 0.034). …


Evaluating Blood Pressure Methods In Non-Traumatic Intracerebral Hemorrhage: A Two-Site Prospective Observational Study, Desiree Cihelka May 2024

Evaluating Blood Pressure Methods In Non-Traumatic Intracerebral Hemorrhage: A Two-Site Prospective Observational Study, Desiree Cihelka

Theses and Dissertations (ETD)

Purpose. Blood pressure (BP) management is difficult and complex in the treatment of acute non-traumatic intracerebral hemorrhage (ICH). Despite mean arterial pressure (MAP) being the most reliable measure of noninvasive automatic oscillometric (NIBP) in clinical practice, clinicians instead rely on systolic and diastolic blood pressure (SBP and DBP) values to guide clinical practice. Given the widespread use of NIBPs for obtaining BP values in the acute care setting, we determine the agreement between SBP, DBP, and MAP measured by NIBP, manual cuff, and Arterial lines (A-lines) in patients with ICH. Study Aims. To understand the agreement between SBP, DBP, and …