Medical Specialties Commons^™

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Immune Dynamics And B Cell Contributions To Neuroplasticity And Recovery After Stroke, Thomas A. Ujas

Theses and Dissertations--Neuroscience

This dissertation explores the dynamic interplay between the immune system and the brain across stroke and aging using clinical, post-mortem, and pre-clinical models. The immune system plays critical roles in shaping brain function, responding to injury, and mediating recovery. These studies aim to enhance our understanding of neuroimmune dynamics across spatial and temporal dimensions.

In the first part, we conducted longitudinal sampling of aneurysmal subarachnoid hemorrhage (aSAH) patients to track immune cell and cytokine changes at days 3, 5, 7, 10, and 14 post-stroke, with a focus on delayed cerebral ischemia (DCI), a common complication. We observed distinct temporal patterns, …

Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn

Theses and Dissertations--Physiology

Heart failure has diverse underlying etiologies, complicating research. While some types, like ischemic disease or inherited mutations, are well-studied, research on rarer forms has lagged. Understanding the molecular drivers in these populations may enhance diagnostics and therapies. This work examines two rare groups: patients with ATTR cardiac amyloidosis and those receiving mechanical assist device support. We show that myocardium from patients with amyloidosis has increased fibrosis and reduced force production without changes in cross-bridge kinetics. Additionally, we show that the passive stiffness of amyloidosis myocardium is not different from non-failing myocardium, indicating increased ventricular wall thickness may cause restrictive filling. …

Fabricating Silver-Ceria Polymer Nanocomposite Scaffolds For Biomedical Therapeutic Applications, Shreya S. Pawar

Honors Undergraduate Theses

Improper healing of bone fractures and limited regeneration of bone following bone tumor resection remain a prevalent complication worldwide. Long-term effects of this include joint instability, limited movement, and arthritis. Bone infections (osteomyelitis), reactive oxygen species (ROS) generation via excessive inflammation, and underlying conditions such as osteoporosis can contribute to suboptimal bone tissue regeneration. ROS accumulation stimulates osteoblast apoptosis, while promoting osteoclast differentiation. These processes inhibit mineralization and osteogenesis. Conventional therapeutics involve the utilization of drugs and bone grafts. However, these approaches pose limitations and can result in subsequent complications. Microbial infections, ROS accumulation, and excessive inflammations are factors that …

Recombinant Factor Viia: New Insights Into The Mechanism Of Action Through Product Innovation, Miguel A Escobar, Maureane Hoffman, Giancarlo Castaman, Cedric Hermans, Johnny Mahlangu, Johannes Oldenburg, Charles L Percy, Mark T Reding, Amy D Shapiro, Steven W Pipe

Faculty, Staff and Student Publications

Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents, including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslational modifications. Although rFVIIa has been used to manage bleeding in persons with hemophilia and inhibitors for over 30 years, its mechanisms of action is still being studied. In vitro and in vivo studies have suggested that rFVIIa could promote hemostasis by (1) increasing tissue factor-dependent activation of factor (F)X …

Serglycin Controls Megakaryocyte Retention Of Platelet Factor 4 And Influences Megakaryocyte Fate In Bone Marrow, Joshua Lykins, Isabelle C. Becker, Virginia Camacho, Hammodah Rawhi Hammodah Alfar, Joonwoo Park, Joseph Italiano, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Megakaryocytes (MKs) produce platelets, and similar to other hematopoietic progenitors, they are involved in homeostatic aspects of their bone marrow niche. MKs release and endocytose various factors, such as platelet factor 4 (PF4)/CXCL4. Here, we show that the intra-α-granular proteoglycan, serglycin (SRGN), plays a key role in this process by retaining PF4, and perhaps other factors, during MK maturation. Immature, SRGN–/– MKs released ~80% of their PF4, and conditioned media from these cells negatively affected wild-type MK differentiation in vitro. This was replicated in wild-type MKs by treatment with the polycation surfen, a known inhibitor of glycosaminoglycan (GAG)/protein interactions. In …

Abcg5/Abcg8-Independent Mechanisms Fail To Maintain Sterol Balance In Mice Fed A High-Cholesterol Diet, Garrett B. Anspach, Rupinder Kaur, Isha Chauhan, Erika L. Savage, Brittney Poole, Victoria P. Noffsinger, Xiaoming Fu, Zeneng Wang, Clairity Voy, Ryan E. Temel, Scott M. Gordon, Robert N. Helsley, Gregory A. Graf

Saha Cardiovascular Research Center Faculty Publications

The ABCG5/ABCG8 (G5G8) sterol transporter opposes the accumulation of dietary xenosterols but is also the primary mediator of biliary cholesterol secretion. In humans and in mouse models of disrupted biliary cholesterol secretion, fecal neutral sterols (FNSs) remain constant, indicating the presence of an alternate pathway for cholesterol excretion. Transintestinal cholesterol elimination or excretion (TICE) is thought to compensate for biliary disruptions and G5G8 insufficiency. We sought to measure the compensatory increase in intestinal cholesterol secretion and provide mechanistic insight for how TICE maintains sterol balance in the absence of hepatic G5G8. Differences were not observed in FNSs between control, acute, …

Obesity Prediction From Structural Mri Using Conformal Deep Learning With Uncertainty Quantification, W. Farzana, A. G. A. Temtam, B. Humud-Arboleda, L. Ma, M. Bean, F. Gerard Moeller, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Obesity arises from a neurobehavioral disorder in which the brain’s regulation of hunger and food intake is impaired, leading to an imbalance between energy consumption and expenditure. One key phenotype associated with obesity is body mass index (BMI). BMI is influenced by multiple causal pathways driven by behavioral, metabolic, and genetic factors. Traditional obesity prediction studies often rely on magnetic resonance imaging (MRI) voxel-based morphometry to correlate BMI with obesity-related clinical measurements and brain structure, predominantly gray matter volume (GMV). However, the altered brain regions are variable and widespread between studies, with some literature presenting contradictory results between BMI and …

Identification Of Potential Prophylactic Medical Countermeasures Against Acute Radiation Syndrome (Ars), Kia T. Liermann-Wooldrik, Arpita Chatterjee, Elizabeth A. Kosmacek, Molly Myers, Oluwaseun Adebisi, Louise Monga-Wells, Liu Mei, Michelle P. Takacs, Patrick H. Dussault, Daniel R. Draney, Robert Powers, James W. Checco, Chittibabu Guda, Tomáš Helikar, David B. Berkowitz, Kenneth W. Bayles, Alan H. Epstein, Lynnette Cary, Daryl J. Murry, Rebecca E. Oberley-Deegan

Journal Articles: Pathology and Microbiology

Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro …

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

Cervical Ripening In Nulliparous, Healthy, Full-Term Pregnant Women: The Impact Of Oral Evening Primrose, Ghada Abdelmaksoud Badr, Magdy Hassan Balaha, Ramy Mohamed Elnaggar, Sherin Barakat Elbahoty

Journal of Medicine in Scientific Research

Background Seeds of the evening primrose plant (Oenothera biennis) are used to make evening primrose oil (EPO) capsules. EPO's omega-6 essential fatty acids are mostly responsible for their therapeutic advantages since they have an impact on prostaglandin and cytokine synthesis. The purpose of this study was to assess how EPO affected cervical ripening in healthy nulliparous women who were carrying fullterm pregnancies. Methods A single-blinded randomized controlled trial was conducted involving 110 healthy nulliparous women, all with a Bishop score of 6 or lower, singleton pregnancies, cephalic presentations, and no signs of cephalo-pelvic disproportion. Participants were split into two equal …

Proximal Chronic Total Occlusion Of The Left Anterior Descending Coronary Artery: Conventional Vs. Minimally Invasive Revascularization, Ahmed Shafeek Ali, Mahmoud Maher Abdou Ibrahim, Haitham Alshahat Ramadan

Journal of Medicine in Scientific Research

Introduction Minimally invasive techniques have gained much popularity in recent years. Our goal is comparing the initial outcomes of the minimally invasive technique to the traditional method for managing chronic total occlusion of the left anterior descending coronary artery. Methods A total of 60 ischemic individuals with isolated chronic total occlusion (CTO) of the left anterior descending coronary artery and a history of failed PCI were prospectively studied at the National Heart Institute, Cairo, Egypt, between June 2021 to November 2023. Patients were matched using EuroSCORE II, all patients were operated on utilizing the off-pump technique. Group 1 encompassed 30 …

Hand Grip Strength As A Predictor Of Pulmonary Function In Children With Congenital Heart Disease: A Cross-Sectional Study, Taher S.E. Taha, Abeer El Sayed Hamed, Mohamed Ahmed Omar, Shymaa Mahmoud Maaty

Journal of Medicine in Scientific Research

Background Children with congenital heart disease (CHD) frequently present with reduced pulmonary function due to cardiopulmonary impairments and decreased physical activity levels. Peripheral muscle weakness is common and may reflect overall respiratory performance. Aim To examine the correlation between hand grip strength (HGS) and pulmonary function parameters in pediatric CHD patients. Settings and Design In this cross-sectional study, 50 children aged 6–14 years with confirmed CHD were recruited from the National Heart Institute, Egypt. Methods and Material Pulmonary function tests were conducted using a calibrated spirometer, measuring FVC, FEV1, PEF, FEV1/FVC ratio, and MMV. HGS was assessed using a hydraulic …

One And Half Versus Bi-Ventricular Repair In Pediatric E Bstein Anomaly, Short-Term Outcomes Retrospective Analysis, Rania Abushokka, Hanan Mohammed Hassan, Ahmed Meawad, Ahmed Algebaly

Journal of Medicine in Scientific Research

-Background: The application of one and half-ventricular repair in Ebstein anomaly(EA) should be considered, in association with effective cone repair, to reduce the volume preload on a dysfunctional right ventricle, and to take the benefit of obtaining ante-grade pulmonary blood flow. The one and half-ventricular repair that applied in patients with hypoplastic sub pulmonic ventricle can alternate effectively the Fontan pathway. This provides pulsatility in pulmonary circulation. However, pressure elevation in superior vena cava (SVC) and right atrial hypertension can occur in patient’s undergone one and half ventricular repair. Aim The aim of this study to evaluate the short-term outcomes …

Impact Of Body Mass Index On Echocardiographic Parameters Of Patients With Ischemic Cardiomyopathy, Rehab M Al-Ashry, Mohamed Elbayomi, Nesreen M. Zakaria

Journal of Medicine in Scientific Research

Background: Since obesity raises the risk of several metabolic and cardiovascular disorders, it is a serious global health concern. Researches on its effects on heart anatomy, function, and metabolic parameters in ischemic cardiomyopathy patients are still ongoing. Aim: To assess how elevated body mass index (BMI) is related to echocardiographic parameters in patients with ischemic cardiomyopathy. Methods: There were two patient groups in this investigation with ischemic cardiomyopathy: overweight/obese (Group I, BMI >25) and non-obese (Group II, BMI ≤25). Echocardiographic measurements, comprising systolic and diastolic performance, wall thickness, and left and right ventricular dimensions were evaluated. Laboratory parameters, including glycemic …

Utility Of Platelet And Lymphocyte Indices Among Dengue Seropositive Patients, Lionel Rohit Mathew, Hemnath Rajkumar, Varshaa Chithrra, Pavithra Murugan, Nalini Peravali, Ashwini Suruthy, Madeeha Tahseen, Arthy Subramanian, Shalini Karthikeyan, Sridevi Vijayasankar, Mahendranath Pernati, Saraswathi Manikam

Journal of Medicine in Scientific Research

Introduction: Dengue Fever is a common mosquito-borne viral infection that causes epidemics in countries like India [1]. Dengue Hemorrhagic Fever and Dengue Shock Syndrome are life-threatening complications where a sudden drop in platelet count leads to plasma leakage and bleeding manifestations [2, 3].Platelet Count, Platelet indices, Total Leucocyte Count and Lymphocyte Count are useful for the early diagnosis and prognosis of Dengue Fever [3, 4]. Aim: The aim of the study is to assess the utility of Platelet and Lymphocyte parameters among the Dengue-Seropositive patients. Methodology: This is a longitudinal observational study done in the Department of Pathology in Sri …

Effect Of Integrated Neuromuscular Inhibition Technique On Iliotibial Band Friction Syndrome, Esraa Tarek Farouk Ahmed, Amir Mohamed Saleh, Hassan Hussien Ahmed, Doaa Rafat El Azab

Journal of Medicine in Scientific Research

Background: It was reported that, 25% of adults experience limited mobility and a diminished quality of life due to knee pain. The iliotibial band friction syndrome (ITBFS) is a frequent overuse injury that causes lateral knee pain. It is marked by recurrent lateral knee pain as well as motor impairment in the lower extremities. Pain worsens with exercise and weight-bearing activities, especially at 30° of knee flexion, and patients usually have a history of overuse caused by knee flexion and extension.Objective: To determine the impact of the integrated neuromuscular inhibition technique on pain intensity, knee range of motion and knee …

Endoscopic Management Of Third Ventricular Colloid Cysts: Efficacy, Safety, Technique, Result, And Limitations, Mohammad Abdulsalam Soliman

Journal of Medicine in Scientific Research

Background: Colloid cysts of the third ventricle are rare, benign lesions that may cause life-threatening obstructive hydrocephalus. Full-endoscopic resection has emerged as a minimally invasive alternative to microsurgical approaches. This study evaluates the surgical outcomes and safety profile of the trans-frontal endoscopic technique, with emphasis on the swiveling technique for capsule excision. Methods: This retrospective and prospective cohort study included 24 patients who underwent full-endoscopic trans-frontal resection of third ventricular colloid cysts at Al- Ahrar Teaching Hospital, a tertiary neurosurgical center in Egypt, between January 2016 and December 2024. All procedures were performed using a 6° angled rigid neuroendoscopy with …

Contact Pathway Factors As Potential Modifiers Of Bleeding Related To Factor Xi Deficiency, Ivy R. Han, Leah Rosenfeldt, Courtney Young, Bal Krishan Phd, Rachel Cantrell Phd, Cassie Sprague, Mousa Kharnaf, William Abplanalp, Joseph Palumbo Md

Williams Honors College, Honors Research Projects

Factor XI (FXI) deficiency, also known as Hemophilia C, is characterized by mild to moderate bleeding symptoms. However, the factors that modify bleeding severity in FXI deficiency are not fully understood. In this study, we investigated whether components of the contact activation pathway can act as modifiers of bleeding in the context of FXI deficiency. Using a tail vein transection (TVT) model in rats, we assessed bleeding in four experimental groups: wild-type Sprague-Dawley rats, Prekallikrein knockout (PKK^-/-) rats, rats treated with a FXI-inhibiting antibody, and PKK-/- rats treated with the FXI antibody.

Under anesthesia, each rat underwent a …

Depletion Of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy, Joseph Rupert, Alexes Daquinag, Yongmei Yu, Yulin Dai, Zhongming Zhao, Mikhail G Kolonin

Faculty, Staff and Student Publications

This study shows that populations of CAFs have distinct effects on pancreatic cancer progression and shows that depletion of CAFs expressing adipose markers potentiates tumor/metastasis suppression effects of immune checkpoint blockade.

Tagraxofusp Maintenance Post-Hematopoietic Stem Cell Transplantation Provides Long-Term Survival And Manageable Safety For A Patient With Blastic Plasmacytoid Dendritic Cell Neoplasm, Qaiser Bashir, Marina Konopleva, Glorette Abueg, Jeremy Ramdial, Chitra Hosing, Samer A Srour, Amin Alousi, Uday R Popat, Yago Nieto, Gheath Alatrash, Richard E Champlin, Elizabeth J Shpall, Muzaffar Qazilbash, Naveen Pemmaraju

Faculty, Staff and Student Publications

Presented here is the case of a 68-year-old woman with blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG) maintenance therapy post-allogeneic hematopoietic stem cell transplantation (allo-HCT). Prior to allo-HCT, the patient was treated with hydroxyurea and mini-CVD (cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate (Methotrexate) and cytarabine) + venetoclax + TAG for 5 cycles, which induced morphologic complete remission with minimal residual disease. After allo-HCT, the patient had persistent cytogenic abnormalities 45,XX,der(7)add(7)(p13)del(7)(q11.2q22)add(7)(q32),add(12)(p13),-15,del(16)(q23),-17,+22,+2mar[1]/46,XX[19], and was then treated with TAG maintenance therapy at 9 mg/kg on a 28-day cycle for 16 cycles. At mid-treatment (cycle 6 of 16 cycles of …

Co-Morbid Indomethacin-Responsive Headaches In A Woman In Her Late 60s With Paroxysmal Hemicrania And Hypnic Headache: A Case Report, Ashlyn Brown, Randolph W Evans, Claudia Carrizo, Mark Burish

Faculty, Staff and Student Publications

Paroxysmal hemicrania (PH) and hypnic headache (HH) are rare indomethacin-responsive headache syndromes. This case report details the new onset of both disorders in a woman in her late 60s. One headache type presented as severe pain centered on the right eyebrow, lasting 30 minutes, occurring more than 8 times daily, and associated with ipsilateral lacrimation and rhinorrhea. The second type was a right frontal severe pain, with onset at 4 a.m., occurring only during sleep, lasting 30 minutes, and with no associated factors. The patient's response to indomethacin for both headache types was confirmed through an unblinded ABAB study design: …

Key Considerations For Combination Therapy In Alzheimer’S Clinical Trials: Perspectives From An Expert Advisory Board Convened By The Alzheimer’S Drug Discovery Foundation, Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew Von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit

Faculty, Staff and Student Publications

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress …

Effect Of Non-Complicated Cataract Extraction With Phacoemulsification On Central Macular Thickness (Cmt) And Ganglion Cell Complex (Gcc) In Non-Diabetic Patients At Sohag Teaching Hospital, Mohammed Shikhoun Ahmed, Mariam Kamal

Journal of Medicine in Scientific Research

Background: Cataracts are widely acknowledged as the primary cause of blindness on a global scale. Cataract surgery, particularly phacoemulsification, is the most effective and the only approved intervention for cataracts, regardless of etiology. Phacoemulsification, with its numerous advantages, is the most widely used method for cataract removal. It is important to note that while phacoemulsification is considered a safe and effective procedure, there are potential complications that need to be managed. Methods: This study included one hundred eyes of 93 nondiabetic patients undergoing noncomplicated cataract operation at the ophthalmology department at Sohag Teaching Hospital. A preoperative assessment of the best …

Implications And Pathophysiology Of Neuroinflammation In Pediatric Patients With Traumatic Brain Injury: An Updated Review, Shalin S Shah, Arya J Shetty, David T Johnston, Caroline L Hanan, Brendan T O'Reilly, Max A Skibber, Ahmed T Massoud, Banghe Zhu, Eva M Sevick-Muraca, Jenifer Juranek, Charles S Cox, Manish N Shah

Faculty, Staff and Student Publications

Traumatic Brain Injury (TBI) in children is a profound public health issue with the potential to disrupt cognitive, behavioral, and psychosocial development significantly. This review provides an updated examination of the role of neuroinflammation in pediatric TBI, emphasizing its dual impact on injury progression and recovery. Highlighted is the complex interplay of primary and secondary injury mechanisms, including the critical contributions of neuroinflammatory responses mediated by central and peripheral immune cells. Advances in biomarker identification and imaging techniques are discussed, showcasing how tools like diffusion tensor imaging (DTI) and positron emission tomography (PET) enhance our understanding of neuroinflammatory processes. The …

Investigating The Role Of Prostasin In Angiogenesis: A Chorioallantoic Membrane Model Approach, Zaima Aline

Honors Undergraduate Theses

Prostasin, also known as PRSS8 or CAP1, is a glycosylphosphatidylinositol (GPI)-anchored extracellular serine protease involved in various physiological and pathophysiological processes. Prostasin expression is observed during key phases of trophoblast invasion and placental development, critical steps in embryo implantation in Rhesus monkeys. This suggests a role for prostasin in extracellular matrix remodeling and tissue invasion, both essential for a healthy pregnancy. Moreover, prostasin appears vital for development as studies in mice show that a germline knockout of the gene leads to significant placental defects and eventual embryonic death, highlighting its importance in vascular and structural development within the placenta.

Building …

Facilitation Of Chemotherapy Efficacy Through Targeted Drug Delivery In Lung Cancer Cells Via Ultrasound And Implications On Health Interventions, Ibrahim Nasim

Honors Undergraduate Theses

Lung Cancer (small cell and non-small cell) is the leading cause of cancer death in the US, accounting for about 20% of all cancer deaths. Paclitaxel (PTX) is a chemotherapeutic agent commonly used to treat lung cancer. It works by slowing and stopping cancer growth by stiffening microtubules within cells, promoting mitotic halt and cell death. Carboplatin (CP) is another agent given to lung cancer patients containing platinum and works via direct damage of oncolytic DNA. The exact mechanism of how PTX and CP cause cell death is still an under-studied area. This thesis aims to provide insight into how …

Meta-Analysis Of The Effect Of Vagus Nerve Stimulation On Functional Heart Failure Outcomes, Ariana B. Labrada

Honors Undergraduate Theses

Globally, Heart Failure (HF) is a significant cause for concern. Vagus Nerve Stimulation (VNS) is an emerging therapy for patients with HF. It involves the activation of efferent vagal signals, which result in the release of acetylcholine (ACh). In practice, VNS has obtained relatively mixed results in clinical trials so far. In order to ascertain the extent of the effects VNS has on functional clinical outcomes, this meta-analysis consolidates studies that involve patients with Heart Failure with reduced Ejection Fraction (HFrEF) and Heart Failure with preserved Ejection Fraction (HFpEF). Outcomes were measured through the change in mean heart rate (HR) …

High-Throughput Drug Screening For Disease-Modifying Arthritis Therapy, Janapriya Vijayakumar

Honors Undergraduate Theses

Current therapy for arthritis predominantly focuses on the symptoms rather than the underlying causes of disease progression. Thus, it is necessary to identify novel drugs which target the underlying molecular basis of such diseases. Using high-throughput cell-based drug screening, we screened 458 different compounds, narrowed down from 811 starting compounds from the NIH Mechanistic Set. We selected drugs from the Mechanistic Set following Lipinski's Rule of 5 to ensure optimal pharmacokinetic properties. The study used modified primary human chondrocytes (IIAM-PRG4Luc), which secrete a lubricin promoter-driven luciferase reporter. We use this luciferase expression as a proxy to measure lubricin, a compound …

Investigation Of Lubricin-Stimulating Fda-Approved Compounds For A Disease-Modifying Osteoarthritic Drug, Swathi S. Menon

Honors Undergraduate Theses

Osteoarthritis (OA) is a degenerative disease that affects many people worldwide. Current methods of treatment are palliative, and no treatment exists to fully reverse or cure OA once it begins to progress. The discovery of a disease-modifying osteoarthritic drug (DMOAD) would increase the quality of life for millions and reduce the need for invasive procedures. Screening FDA-approved drugs ensures more promise due to their known safety profile and potential for faster translation to the clinic. The goal of this project was to conduct dose-response assays with FDA-approved drugs that have been shown to stimulate lubricin production in cells that mimic …