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The State Of The Translational Chaperone Icd-1 During Apoptosis In Caenorhabditis Elegans, Kyle Cicalese May 2018

The State Of The Translational Chaperone Icd-1 During Apoptosis In Caenorhabditis Elegans, Kyle Cicalese

Senior Honors Projects, 2010-2019

The unfolded protein response (UPR) is a signal transduction cascade that mitigates low levels of misfolded protein stress in the endoplasmic reticulum (ER) in an effort to save the affected cell, while prolonged and/or acute ER stress leads to UPR-initiated apoptosis (programmed cell death). One putative step driving apoptosis is the cleavage of chaperones, proteins tasked to help misfolded proteins refold, by caspases, proteases essential to the execution of apoptosis. We are studying the nascent polypeptide-associated complex (NAC), a heterodimeric chaperone complex essential for viability, to determine if its beta subunit is cleaved by caspases during apoptosis to prevent the …


Evolution Of Bordetella Pertussis Genome May Play A Role In The Increased Rate Of Whooping Cough Cases In The United States, Kevin Loftus May 2018

Evolution Of Bordetella Pertussis Genome May Play A Role In The Increased Rate Of Whooping Cough Cases In The United States, Kevin Loftus

Senior Honors Projects, 2010-2019

Bordetella pertussis is the bacterium responsible for pertussis, a disease commonly referred to as whooping cough. Recently, pertussis has made a resurgence in the U.S. despite high-vaccination coverage. Possible causes of the increased number of pertussis cases include genetic evolution of B. pertussis, increased awareness of the disease, better laboratory diagnostics, and the switch from a whole-cellular (wP) vaccine to an acellular vaccine (aP) in the 1990s. Fortunately, just as B. pertussis is evolving, so is the arsenal of technologies used to understand and combat this pathogenic bacterium. Whole genome sequencing is one technology that helps researchers better understand …


Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson May 2018

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …


Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, Michael Price May 2018

Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, Michael Price

Theses & Dissertations

Alcohol abuse, which can impair clearance of pathogens and debris from the airway, is associated with an increase in complications and a higher mortality rate during the progression of pneumonia. With prolonged alcohol exposure, mucociliary clearance (MCC), which depends on the coordinated beating of cilia, is dysfunctional. Effective MCC relies on cAMP-dependent protein kinase (PKA) activation of ciliary beat frequency (CBF). PKA activation and stimulation of CBF are blunted with chronic exposure to alcohol. This phenomenon is known as alcohol-induced ciliary dysfunction (AICD). Previous studies have shown that concomitant feeding of mice with alcohol and antioxidants prevents AICD, suggesting a …


The Effect Of Dust Mite Extract On Esophageal Tight Junctions In Eosinophilic Esophagitis, Kyle Hinz May 2018

The Effect Of Dust Mite Extract On Esophageal Tight Junctions In Eosinophilic Esophagitis, Kyle Hinz

Theses & Dissertations

Eosinophilic Esophagitis (EE) is a chronic inflammatory disease that effects individuals of all ages. EE is mediated by an allergen response, causing the release of thymic stromal lymphopoietin (TSLP), and subsequent inflammation and eosinophil migration and infiltration of the esophagus through the activation of the JAK/STAT pathway and CD4+ T-cells. EE has typically been associated with food allergies, but studies have shown that aeroallergens can cause EE as well. Current treatments of EE have primarily focused on nonspecific methods, though anti-TSLP is beginning to be tested as a possible treatment for EE. The aim of this study was to see …


Muc4 Based Immunotherapy For Pancreatic Cancer, Kasturi Banerjee May 2018

Muc4 Based Immunotherapy For Pancreatic Cancer, Kasturi Banerjee

Theses & Dissertations

Pancreatic Cancer (PC) is a lethal disease claiming approximately 45000 lives in the US in 2018, and it establishes an elaborate immunosuppressive tumor microenvironment that aids in disease pathogenesis. Immunotherapy has emerged as a strategy to target tumor cells by reprogramming patient’s immune system. Challenges present in PC immunotherapy are: i) identifying a tumor-associated antigen that could be targeted, ii) identifying adjuvants that could efficiently deliver antigens, iii) eliciting robust anti-tumor responses and iv) overcoming peripheral tolerance and immunosuppression elicited by the tumor.

Firstly, we detected circulating autoantibodies to MUC4 present in PC patients and observed that IgM autoantibodies to …


The Beta-Catenin/Muc1.Ct Interaction In Pancreatic Cancer, Edwin Wiest May 2018

The Beta-Catenin/Muc1.Ct Interaction In Pancreatic Cancer, Edwin Wiest

Theses & Dissertations

MUC1 is overexpressed in over 90% of pancreatic cancer cases, and its interaction with beta-catenin promotes progression of the disease. Various in vitro and in vivo methods show that beta-catenin and MUC1 interact by way of the cytoplasmic tail of MUC1 (MUC1.CT). This interaction occurs in the membrane of pancreatic cancer cells but is found to a smaller extent in the nucleus as well. Biophysical methods suggest that MUC1 interacts with beta-catenin through a sequence of amino acids in the tail of MUC1 that sit very near the transmembrane domain of MUC1. In pancreatic ductal adenocarcinoma cells, it appears that …


Abrogation Of Transforming Growth Factor-Β-Induced Tissue Fibrosis In Tbricacol1a2cre Transgenic Mice By The Second Generation Tyrosine Kinase Inhibitor Ski-606 (Bosutinib)., Peter J. Wermuth, Sergio A. Jimenez May 2018

Abrogation Of Transforming Growth Factor-Β-Induced Tissue Fibrosis In Tbricacol1a2cre Transgenic Mice By The Second Generation Tyrosine Kinase Inhibitor Ski-606 (Bosutinib)., Peter J. Wermuth, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Transforming growth factor-β (TGF-β) plays a crucial role in the pathogenesis of Systemic Sclerosis (SSc) and other fibrotic disorders. TGF-β-mediated c-Abl and Src kinase activation induces strong profibrotic cascade signaling. The purpose of this study was to test in vivo the antifibrotic activity of Bosutinib (SKI-606), a second generation c-Abl and Src kinase inhibitor, on TGF-β induced cutaneous and pulmonary fibrosis. For this purpose, we employed the TBRIcaCol1a2Cre transgenic mice expressing an inducible constitutively active TGF-β receptor 1 constitutively activated by Col1a promoter-mediated Cre recombinase. The mice were treated parenterally with 2.5, 5.0 or 10.0 mg/kg/day of Bosutinib for 42 …


Treating Adhd With Suggestion: Neurofeedback And Placebo Therapeutics, Robert T. Thibault, Samuel Vassière, Jay A. Olson, Amir Raz May 2018

Treating Adhd With Suggestion: Neurofeedback And Placebo Therapeutics, Robert T. Thibault, Samuel Vassière, Jay A. Olson, Amir Raz

Psychology Faculty Articles and Research

Objective: We propose that clinicians can use suggestion to help treat conditions such as ADHD. Methods: We use EEG neurofeedback as a case study, alongside evidence from a recent pilot experiment utilizing a sham MRI scanner to highlight the therapeutic potential of suggestion-based treatments. Results: The medical literature demonstrates that many practitioners already prescribe treatments that hardly outperform placebo comparators. Moreover, the sham MRI experiment showed that, even with full disclosure of the procedure, suggestion alone can reduce the symptomatology of ADHD. Conclusion: Non-deceptive suggestion-based treatments, especially those drawing on accessories from neuroscience, may offer a safe complement and potential …


The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, Md May 2018

The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, Md

Department of Pathology Honors Program Student Research Symposium

Background: Spectral Domain Optical Coherence Tomography (SD-OCT) has become a gold standard technique in ophthalmologic practice, and has revolutionized the diagnosis and treatment of retinal disease. As SD-OCT uses low interference interferometry and mathematical algorithms to produce detailed theoretical cross-sectional images of the retina, it is crucial to examine correlations between SD-OCT images and their corresponding histopathologic slides.

Methods: In the present study, careful correlative light microscopy was performed on the eye that was enucleated from an elderly patient who had a uveal melanoma and early agerelated macular degeneration evident clinically as soft drusen. SD-OCT was performed prior to enucleation …


The Small Rna Complement Of Adult Schistosoma Haematobium., Andreas J Stroehlein, Neil D Young, Pasi K Korhonen, Ross S Hall, Aaron R Jex, Bonnie L Webster, David Rollinson, Paul J Brindley, Robin B Gasser May 2018

The Small Rna Complement Of Adult Schistosoma Haematobium., Andreas J Stroehlein, Neil D Young, Pasi K Korhonen, Ross S Hall, Aaron R Jex, Bonnie L Webster, David Rollinson, Paul J Brindley, Robin B Gasser

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans.

METHODOLOGY: MicroRNAs (miRNAs) and other …


The Use Of Liquid Biopsy In The Fight Against Cancer, Chamaka Kalutota, Emanual Rubin, Md May 2018

The Use Of Liquid Biopsy In The Fight Against Cancer, Chamaka Kalutota, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

In recent years, liquid biopsy has emerged as a potential alternative/adjunct to standard tissue biopsy in the diagnosis of malignancies. Current use of this technique, which tracks distinctive molecules released from neoplastic cells including circulating tumor cells (CTCs), exosomes, circulating tumor DNA (ctDNA), cell-free DNA (cfDNA) and miRNA, has generally been limited to determining therapies in lung cancer based on detectable mutations (EFGR, EML4-ALK). However, recent studies have demonstrated the possibility for using these molecules as more efficient prognostic and diagnostic biomarkers in breast, colon, rectum, lung, liver, and pancreatic cancer. Due to the need for standardization in sampled material …


Interferon-Gamma Impairs Maintenance And Alters Hematopoietic Support Of Bone Marrow Mesenchymal Stromal Cells, Marieke Goedhart, Anne S. Cornelissen, Carlijn Kuijk, Sulima Geerman, Marion Kleijer, Jaap D. Van Buul, Stephan Huveneers, Marc H.G.P. Raaijmakers, Howard A. Young, Monika C. Wolkers, Carlijn Voermans, Martijn A. Nolte May 2018

Interferon-Gamma Impairs Maintenance And Alters Hematopoietic Support Of Bone Marrow Mesenchymal Stromal Cells, Marieke Goedhart, Anne S. Cornelissen, Carlijn Kuijk, Sulima Geerman, Marion Kleijer, Jaap D. Van Buul, Stephan Huveneers, Marc H.G.P. Raaijmakers, Howard A. Young, Monika C. Wolkers, Carlijn Voermans, Martijn A. Nolte

United States Public Health Resources

Bone marrow (BM) mesenchymal stromal cells (MSCs) provide microenvironmental support to hematopoietic stem and progenitor cells (HSPCs). Culture-expanded MSCs are interesting candidates for cellular therapies due to their immunosuppressive and regenerative potential which can be further enhanced by pretreatment with interferon-gamma (IFN-γ). However, it remains unknown whether IFN-γ can also influence hematopoietic support by BM-MSCs. In this study, we elucidate the impact of IFN-γ on the hematopoietic support of BM-MSCs. We found that IFN-γ increases expression of interleukin (IL)-6 and stem cell factor by human BM-MSCs. IFN-γ-treated BM-MSCs drive HSPCs toward myeloid commitment in vitro, but impair subsequent differentiation of …


Loss Of The Na+/H+ Exchange Regulatory Factor 1 Results In Increased Susceptibility To Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle May 2018

Loss Of The Na+/H+ Exchange Regulatory Factor 1 Results In Increased Susceptibility To Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle

Electronic Theses and Dissertations

Background. Acute kidney injury (AKI), an abrupt loss of kidney function which carries a high mortality and confers an increased risk of chronic kidney disease, develops in 30% of patients who receive cisplatin, a widely used chemotherapeutic agent [1], [2], [3]. The sodium hydrogen exchange regulatory factor isoform 1 (NHERF1) is a scaffolding protein that anchors multiple membrane proteins, in renal proximal tubules [4]. NHERF-1 deficient mice have aberrant localization of BBM proteins in intracellular compartments [5]. The investigators have recently demonstrated NHERF1 deficient proximal tubule cells have an underlying …


Investigation Into The Role Of Platelet Derived Growth Factor (Pdgf) In Type I Collagen Glomerulopathy, Isaac C. Springer May 2018

Investigation Into The Role Of Platelet Derived Growth Factor (Pdgf) In Type I Collagen Glomerulopathy, Isaac C. Springer

Graduate Theses/Dissertations

Progressive accumulation of collagen and extracellular matrix (ECM) proteins within renal glomeruli have implications for or result in renal fibrosis and glomerulosclerosis, with both events culminating in renal failure. To model this accumulation the Col1a2-deficient mouse model was used. The Col1a2-deficientmouse model is characterized by a mutation in the a2(I) chain, preventing incorporation into the type I collagen molecule. As a result, an α1(I) collagen chain incorporates into the collagen triple helix forming homotrimeric type I collagen, as opposed to heterotrimeric type I collagen. This change is due to the secondary wound healing response in response to ECM accumulation, …


Genome Editing Technology, Crispr Cas-9, Provides A Potential Future For Xenotransplantation: Can Pigs Become Our New Organ Donors?, Shelby Smith, Bs, Emanual Rubin, Md May 2018

Genome Editing Technology, Crispr Cas-9, Provides A Potential Future For Xenotransplantation: Can Pigs Become Our New Organ Donors?, Shelby Smith, Bs, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

Organ shortage has been a significant issue in United States for many decades. There were over 116,000 people on the transplant waiting list as of August 2017, with a new person added every 10 minutes. Animals have been considered as potential organ donors for humans, with the pig being the most ideal candidate because of its excellent breeding profile, low maintenance costs, large litters, rapid growth and organ similarity. A notable challenge that comes with porcine organs are endogenous retroviruses that establish themselves in the DNA of offspring in utero, thereby allowing for no time to prevent infection and integration. …


Acquired Resistance Mutations To Egfr Treatment In Non-Small Cell Lung Cancer, Benjamen Schoenberg, Gregory Omerza, Phd May 2018

Acquired Resistance Mutations To Egfr Treatment In Non-Small Cell Lung Cancer, Benjamen Schoenberg, Gregory Omerza, Phd

Department of Pathology Honors Program Student Research Symposium

Non-small cell lung cancer (NSCLC) is currently the number one cause of cancer death in the United States for both men and women.1 Mutations in the epidermal growth factor receptor (EGFR) gene are detected in approximately 30% of individuals with advanced NSCLC in Asia and 10-15% in Western countries.2 For patients harboring activating EGFR mutations, treatment includes the use of first or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as afatinib, gefitinib, or erlotinib.

The purpose of this case study is to review the pathophysiology of the progression of NSCLC in a 63-year-old non-smoking Caucasian woman. The patient presented with worsening …


A New Frontier In Breast Cancer Management: Oncotype Dx, Gabriella Rollo, Jeremy Molligan, Md, Juan P. Palazzo, Md May 2018

A New Frontier In Breast Cancer Management: Oncotype Dx, Gabriella Rollo, Jeremy Molligan, Md, Juan P. Palazzo, Md

Department of Pathology Honors Program Student Research Symposium

Diagnosing and prognosticating breast cancer has traditionally relied upon histomorphologic analysis and immunohistochemistry. With the recent advent of multigene molecular assays, traditional methods are being augmented with molecular biomarkers. Implementation of the Oncotype DX assay has led to a change in treatment of patients with early stage, estrogen positive cancer. Oncotype DX uses the expression of 21 genes at the mRNA level to determine a 10 year recurrence risk in node negative and 5 year recurrence risk in node positive cancer. 16 malignancy markers related to estrogen, HER2, cell proliferation, and invasion potential are compared with 5 reference genes and …


Primary Cns Small Mature B-Cell Lymphoma With Plasmacytic Differentiation Presenting As An Amyloidoma: A Case Report And Review Of Literature, Andrew Lynch, Geetha Jagannathan, Md May 2018

Primary Cns Small Mature B-Cell Lymphoma With Plasmacytic Differentiation Presenting As An Amyloidoma: A Case Report And Review Of Literature, Andrew Lynch, Geetha Jagannathan, Md

Department of Pathology Honors Program Student Research Symposium

Primary central nervous system lymphomas (PCNSL) without systemic involvement are rare and account for only 2-3% of all brain tumors and <1% of all non-Hodgkin’s lymphoma (NHL). Close to 40% of PCNSL are associated with immunosuppression, however, the incidence of primary central nervous system (CNS) lymphomas has shown an increasing trend in immunocompetent patients in recent decades due to better control of HIV and drug-induced immunosuppression [2]. Here, we describe a case of a primary CNS non-Hodgkin’s small mature B-cell lymphoma with plasmacytic differentiation in an immunocompetent individual. A previously healthy 87-year-old Caucasian woman presented to the neurology clinic with complaints of slowly progressing left sided weakness, predominantly in the left arm and leg over the last 6 months. Magnetic resonance imaging of the brain revealed a large, confluent white matter T2-hyperintensity in the right frontal lobe with multifocal nodular enhancement involving the left cerebral hemisphere, cerebellum, and leptomeninges, consistent morphologically with lymphoplasmacytic lymphoma. A bone marrow biopsy showed normal trilineage hematopoiesis with no evidence of lymphoma, myeloma or amyloidosis. Our patient was treated with Rituximab but developed an ischemic infarct of the left frontal white matter. She and her family decided to forego further treatment and switch to hospice care.


Ewing’S Sarcoma, Chris Lucasti, Bs, Bruce A. Fenderson, Phd May 2018

Ewing’S Sarcoma, Chris Lucasti, Bs, Bruce A. Fenderson, Phd

Department of Pathology Honors Program Student Research Symposium

Ewing’s sarcoma is the second most common malignant tumor of the bone occurring in children and adolescents. Typically, patients present between the ages of 10 and 20, with the disease having a slight predilection for males.1 Tumors often arise in the mid-shaft with the femur being the most frequently affected bone. The most common chromosome translocation, t(11;22)(q24;q12), occurs between the EWS gene and the FLI-1 gene. This translocation has been implicated in these aggressive and malignant tumors.1–4 Oftentimes, patients present with pain and swelling in the area of the affected bone or joint.5 While there has been some improvement in …


Clinico-Pathological Features And Pd-1/Pd-L1 Expression In Primary Mediastinal Large B Cell Lymphoma, Lydia Glick, Geetha Jagannathan, Md, Guldeep Uppal, Md May 2018

Clinico-Pathological Features And Pd-1/Pd-L1 Expression In Primary Mediastinal Large B Cell Lymphoma, Lydia Glick, Geetha Jagannathan, Md, Guldeep Uppal, Md

Department of Pathology Honors Program Student Research Symposium

Primary Mediastinal Large B Cell Lymphoma (PMBCL) is a distinct subtype of Diffuse Large B Cell Lymphoma (DLBCL) that has been historically reported to have a worse prognosis than DLBCL. Occasional studies have reported PD-L1 expression in PMBCL, which can emerge as an important target for immune-check point therapy. This study aimed to evaluate clinico-pathological features and characterize the expression of PD-1 and PD-L1 in a single cohort of 15 patients with PMBCL.

A total of 15 cases of PMBCL were retrieved from records of the department of Pathology; eleven of these had tissue available for additional immunohistochemistry, specifically, PD-L1 …


Comparative Analysis Of Tumor Capsule Thickness And Other Histologic Features In Encapsulated Follicular Variant Of Papillary Thyroid Carcinoma (Efvptc) And Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (Niftp), Brenda French, Stacey K. Mardekian, Md May 2018

Comparative Analysis Of Tumor Capsule Thickness And Other Histologic Features In Encapsulated Follicular Variant Of Papillary Thyroid Carcinoma (Efvptc) And Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (Niftp), Brenda French, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Recent reclassification of a subset of non-invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) tumors as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has led to important changes in the clinical management of patients with these indolent lesions. Although there are established diagnostic criteria to differentiate NIFTP from EFVPTC, our objective was to determine further differences in histological characteristics between NIFTP and noninvasive EFVPTC. Additionally, we sought to identify histological differences between non-invasive and invasive EFVPTC lesions beyond the key finding of invasion. 68 encapsulated follicular lesions with papillary-like nuclear features from patients treated at Thomas Jefferson …


Implications Of Hobnail Features In Anaplastic Thyroid Carcinoma And Precursor Lesions, Caroline Dunne, Ba, Stacey K. Mardekian, Md May 2018

Implications Of Hobnail Features In Anaplastic Thyroid Carcinoma And Precursor Lesions, Caroline Dunne, Ba, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Anaplastic thyroid carcinoma (ATC) has the poorest prognosis of all thyroid cancers. Morphologically, it is characterized by pleomorphic undifferentiated cells. In some cases, a differentiated precursor lesion, either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma, can be identified adjacent to the anaplastic component. There are certain morphological variants of PTC that are known to be associated with more aggressive behavior, but a recently described, understudied variant is the hobnail variant. It is characterized histologically by micropapillary structures lined by cells with abundant eosinophilic cytoplasm and apically-placed bulging nuclei. The aim of this study was to evaluate the frequency of …


Atypical Presentation Of Upshaw Schulman Syndrome: A Case Report, Goutham Ravipati, Bs, David Strayer, Md, Phd, Douglas Drelich, Md May 2018

Atypical Presentation Of Upshaw Schulman Syndrome: A Case Report, Goutham Ravipati, Bs, David Strayer, Md, Phd, Douglas Drelich, Md

Department of Pathology Honors Program Student Research Symposium

Thrombotic thrombocytopenic purpura (TTP) is a rare coagulation disorder with a typical clinical presentation of low platelets and excessive clotting. Mortality for this disorder may be high if untreated and therefore necessitates a high clinical suspicion. Here we describe a 46-year-old African American woman with a past medical history of multiple cerebrovascular accidents presenting to hematology after a suspected diagnosis of TTP. Presumptive diagnosis of acquired TTP called for treatment with IVIg, but a diagnosis of congenital TTP (Upshaw Schulman syndrome) was made after testing showed a lack of ADAMTS13 antibodies. Treatment with fresh frozen plasma (FFP) showed increase in …


Different Methodologies To Characterize And Diagnose Sickle Cell Disease In Both Developed And Developing Nations, Mohammed Alharbi May 2018

Different Methodologies To Characterize And Diagnose Sickle Cell Disease In Both Developed And Developing Nations, Mohammed Alharbi

Dissertations, Masters Theses, Capstones, and Culminating Projects

Sickle cell disease (SCD) is a genetic blood disorder that causes the RBC to become sickle shaped due to a mutation in the β-globin gene encoding the protein hemoglobin. This disease causes reduced oxygen carrying capacity of RBC resulting in painful crisis, hemolytic anemia, and infection susceptibility. SCD affects around 100,000 individuals in USA alone and 14 million people globally. SCD affected individuals have high mortality rates. Early detection and constant monitoring of this disease is essential. The following review focuses on various methodologies that have emerged in the diagnosis of SCD. Also, low cost methods that can be easily …


Implementation Plan To Integrate The Nanosphere Verigene Assay In A High-Volume Reference Laboratory And The Anticipated Workflow Benefits To Adopting Rapid Blood Culture Testing, Sofia Nazar May 2018

Implementation Plan To Integrate The Nanosphere Verigene Assay In A High-Volume Reference Laboratory And The Anticipated Workflow Benefits To Adopting Rapid Blood Culture Testing, Sofia Nazar

Dissertations, Masters Theses, Capstones, and Culminating Projects

Laboratory processing pathways have a significant impact on the overall management of patients with sepsis. Retrieval and isolation of the suspected pathogen from a patient blood culture specimen is required for a definitive diagnosis of bacterial septicemia. Reference laboratories are high-volume facilities most often located some distance away from the collecting facility. Given the lengthy work up already required for blood culture pathogen analysis, reference laboratories must identify ways to optimize every step of the blood culture pathway in the effort to decrease turnaround time and mitigate lag time to final pathogen identification incurred by prolonged collection-to-incubation times. Rapid molecular …


Synaptic Nanomodules Underlie The Organization And Plasticity Of Spine Synapses., Martin Hruska, Nathan T. Henderson, Sylvain J. Le Marchand, Haani Jafri, Matthew B. Dalva May 2018

Synaptic Nanomodules Underlie The Organization And Plasticity Of Spine Synapses., Martin Hruska, Nathan T. Henderson, Sylvain J. Le Marchand, Haani Jafri, Matthew B. Dalva

Department of Neuroscience Faculty Papers

Experience results in long-lasting changes in dendritic spine size, yet how the molecular architecture of the synapse responds to plasticity remains poorly understood. Here a combined approach of multicolor stimulated emission depletion microscopy (STED) and confocal imaging in rat and mouse demonstrates that structural plasticity is linked to the addition of unitary synaptic nanomodules to spines. Spine synapses in vivo and in vitro contain discrete and aligned subdiffraction modules of pre- and postsynaptic proteins whose number scales linearly with spine size. Live-cell time-lapse super-resolution imaging reveals that NMDA receptor-dependent increases in spine size are accompanied both by enhanced mobility of …


Determining The Role Of Point-Of-Care Hemoglobin Testing In The Resuscitation Of Acutely Hemorrhaging Patients, Eugene P. Warnick, Alexis R. Peedin, Md May 2018

Determining The Role Of Point-Of-Care Hemoglobin Testing In The Resuscitation Of Acutely Hemorrhaging Patients, Eugene P. Warnick, Alexis R. Peedin, Md

Department of Pathology Honors Program Student Research Symposium

Point-of-care hemoglobin (Hb) testing has not been evaluated in the resuscitation of acutely hemorrhaging patients to guide transfusion therapy. This study assessed the correlation of Hb values determined by point-of-care (EPOC) and traditional laboratory (CBC) methods in patients undergoing massive transfusion. All patients transfused per the massive transfusion protocol (MTP) between February 2013 and October 2017 were identified. The EPOC result was most often within 1 g/dL of the CBC result when EPOC resulted in a Hb between 7-10 g/dL and when drawn within 15 minutes of the CBC specimen. In patients on MTP with an EPOC Hb between 7-10 …


Metastatic Lobular Breast Carcinoma In A Meningioma: A Case Study, Sara Chapin, Msii, Lawrence C. Kenyon, Md, Phd May 2018

Metastatic Lobular Breast Carcinoma In A Meningioma: A Case Study, Sara Chapin, Msii, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Hormonal relationships between breast carcinoma and meningioma have long been reported in the literature. This association may be related to the widespread expression of progesterone receptors in meningiomas. Indeed, meningiomas are more common in women and may demonstrate increased growth during pregnancy. Women have an increased risk of meningioma following breast carcinoma diagnosis and vice versa. However, much more uncommon is a tumor to tumor metastases of breast carcinoma into a meningioma. We report a case of a 56 year old female with a past medical history of breast cancer, found to have a right sphenoorbital meningioma with metastatic lobular …


Transplantation Of Thioredoxin-1 Exosomes In A Murine Model Of Hind-Limb Ischemia: A Novel Therapeutic Approach, Shubham Kanake May 2018

Transplantation Of Thioredoxin-1 Exosomes In A Murine Model Of Hind-Limb Ischemia: A Novel Therapeutic Approach, Shubham Kanake

Honors Scholar Theses

Peripheral artery disease is one of the most prevalent cardiovascular diseases in the United States and worldwide. It is estimated that over 8 million people in the United States are affected with peripheral artery disease, and up to 40% of people over 80 years old may have some degree of the disease. Peripheral artery disease can increase one’s chances for having other cardiovascular co-morbidities such as coronary artery disease, among others. Current interventional strategies are endovascular treatments such as transluminal angioplasty and stenting, or in more advanced cases peripheral artery bypass grafting. Medical interventions focus on managing symptoms and treating …