Digital Commons Network^™

Examining The Role Of Metabolic Pathways As Therapeutic Modalities For Triple Negative Breast Cancer, Jeremy Andrew Johnson

Theses and Dissertations--Toxicology and Cancer Biology

Triple negative breast cancer (TNBC) comprises 15-20% of breast cancers, affects a younger patient population than other subtypes, and is very aggressive. TNBC is comprised of a diverse group of tumors that have proven refractory to targeted therapy and can be difficult to treat. Patients generally receive neoadjuvant chemotherapy (NAC), surgery, and radiotherapy. The standard of care for NAC includes a taxane, an anthracycline, and/or cyclophosphamide, and administration of NAC has resulted in pathological complete response (pCR) in 30-40% of patients. However, a majority of TNBC patients will not reach pCR and instead have residual disease (RD), which is associated …

Digest Of The Philadelphia College Of Osteopathic Medicine, Philadelphia College Of Osteopathic Medicine

PCOM Digest 2020s

The (2020 No. 1) issue of the digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Updates

• Institutional Heritage: Founders’ Day 2020

• Marking a New Era of Healthcare Education in South Georgia

• Southwest Georgia: A Sense of Place

• Health Care in Rural Georgia

• Class Notes

Host Transcriptional Response To Persistent Infection With A Live-Attenuated Porcine Reproductive And Respiratory Syndrome Virus Strain, Jayeshbhai Chaudhari, Chia-Sin Liew, Aspen M. Workman, Jean-Jack Riethoven, David J. Steffen, Sarah Vitosh-Sillman, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Both virulent and live-attenuated porcine reproductive and respiratory syndrome virus (PRRSV) strains can establish persistent infection in lymphoid tissues of pigs. To investigate the mechanisms of PRRSV persistence, we performed a transcriptional analysis of inguinal lymphoid tissue collected from pigs experimentally infected with an attenuated PRRSV strain at 46 days post infection. A total of 6404 differentially expressed genes (DEGs) were detected of which 3960 DEGs were upregulated and 2444 DEGs were downregulated. Specifically, genes involved in innate immune responses and chemokines and receptors associated with T-cell homing to lymphoid tissues were down regulated. As a result, homing of virus-specific …

Potential Impacts Of Artificial Intelligence On Spine Imaging Interpretation And Diagnosis, David Howard Durrant

Walden Dissertations and Doctoral Studies

Spine and related disorders represent one of the most common causes of pain and disability in the United States. Imaging represents an important diagnostic procedure in spine care. Imaging studies contain actionable data and insights undetectable through routine visual analysis. Convergent advances in imaging, artificial intelligence (AI), and radiomic methods has revealed the potential of multiscale in vivo interrogation to improve the assessment and monitoring of pathology. AI offers various types of decision support through the analysis of structured and unstructured data. The primary purpose of this qualitative exploratory case study was to identify the potential impacts of AI solutions …

A Prospective Study Comparing Tendon-To-Bone Interface Healing Using An Interposition Bioresorbable Scaffold With A Vented Anchor For Primary Rotator Cuff Repair In Sheep., Jeremiah Easley, Christian Puttlitz, Eileen Hackett, Cecily Broomfield, Lucas Nakamura, Michael Hawes, Charles Getz, Mark Frankle, Patrick St Pierre, Robert Tashjian, P Dean Cummings, Joseph Abboud, Derek Harper, Kirk Mcgilvray

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The purpose of this study was to evaluate the biomechanical and histologic properties of rotator cuff repairs using a vented anchor attached to a bioresorbable interpositional scaffold composed of aligned PLGA (poly(l-lactide-co-glycoside)) microfibers in an animal model compared to standard anchors in an ovine model.

METHODS: Fifty-six (n = 56) skeletally mature sheep were randomly assigned to a repair of an acute infraspinatus tendon detachment using a innovative anchor-PLGA scaffold device (Treatment) or a similar anchor without the scaffold (Control). Animals were humanely euthanized at 7 and 12 weeks post repair. Histologic and biomechanical properties of the repairs were …

Evaluating Historical Paradigms Of Sterility In Perinatal Microbiology And Ramifications For Pregnancy Outcomes, Jonathan Greenberg

Wayne State University Dissertations

Next-generation sequencing technologies, especially 16S rRNA gene and metagenomic sequencing have allowed investigations of low microbial biomass tissues of the human body. While these sequencing methodologies have provided large amounts of reliable data for higher microbial biomass sites, such as the mouth, intestine, and vagina, tissues of low microbial biomass sites are subject to specific caveats that were not appropriately considered in early investigations of these sites. Low microbial biomass sites of particular interest have included those of the reproductive and urinary systems. Utilization of DNA sequencing methodologies have allowed researchers to challenge existing paradigms of sterility around these sites …

Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog

Wayne State University Dissertations

The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …

Commentary On: Cosmeceuticals: The Principles And Practice Of Skin Rejuvenation Of Nonprescription Topical Therapy, Clifford P. Clark, Ashley Goldston

Surgery Faculty Publications

No abstract provided.

Anthropogenic Suffering Of Farmed Animals: The Other Side Of Zoonoses, Jean-Jacques Kona-Boun

Animal Sentience

Wiebers & Feigin’s (W&F’s) target article warns of the zoonotic threat to human health from factory farming and urges phasing out meat production and consumption, for the benefit of both human and nonhuman animals. This commentary focuses on the physical and emotional suffering of farmed animals. This varies by species, production system and geographic location, but suffering is there throughout all stages of production — breeding, housing, transport, usage and slaughter. Ubiquitous monitoring of all facilities where farmed animals are kept, with surveillance cameras recording all phases of production would help reduce some forms of suffering. Other forms are caused …

Biopsychological Predictors Of Pain And Function In Patients With Rotator Cuff Conditions, Nicole Cascia

Theses and Dissertations--Rehabilitation Sciences

Predicting worse patient-reported outcomes in those with Rotator Cuff (RC) conditions is dependent on examining both biological and psychological impairments. In order to help determine which biopsychological factors are associated with pain and function in patients with RC related conditions and to determine who may be at an increased risk for worse outcomes after Reverse Shoulder Arthroplasty (RSA), biopsychological associations between patient demographics, scapular motion, humeral motion, RC tear size, pain associated psychological distress, and function were clinically evaluated to investigate prediction models for pain and function. The central hypothesis is that in a group of patients with symptomatic Cuff …

Anterior Cruciate Ligament Injury-Induced Alterations In Inflammation And Muscle Physiology, Emily R. Hunt

Theses and Dissertations--Rehabilitation Sciences

Long term weakness and atrophy of the quadriceps muscle are a direct result of anterior cruciate ligament (ACL) injuries and persist for up to 10 years post injury. Muscle atrophy ensues regardless of ligamentous reconstruction surgery, indicating that muscle atrophy following injury is a function of the ligament rupture and not reconstruction surgery. Elucidating the mechanisms underlying quadriceps atrophy following ACL rupture is crucial for developing interventions to restore proper quadriceps size and mitigate weakness thereby allowing for improved patient function. In addition to understanding the specific mechanisms that contribute to quadriceps atrophy following ACL rupture, the timing of atrophic …

Identifying And Addressing Barriers To Treatment For Child Sexual Abuse Survivors And Their Non-Offending Caregivers, Kate Theimer, Akemi E. Mii, Emily Sonnen, Kelsey Mccoy, Katie Meidlinger, Brittany Biles, T. Zachary Huit, Mary F. Flood, David J. Hansen

Department of Psychology: Faculty Publications

Mental health treatment is a critical part of an effective and compassionate response to the disclosure of child sexual abuse (CSA). Given the vast negative consequences for children and families following CSA, engagement in treatment can benefit youth and their non-offending caregivers. Yet, these families face unique barriers to treatment initiation, adherence, and effectiveness. The identification of these barriers allows clinicians, researchers, and policy makers to increase treatment utilization, engagement, and value. The current review and its recommendations derive from the existing literature combined with knowledge gained from a clinical research team with more than 20 years of experience offering …

Tumor Immunology: Understanding The Immune System And Cancer To Enhance The Efficacy Of Cancer Immunotherapies, Natasha Malibu Lenart

Master's Theses

Tumor cells are notorious for their ability to escape immune surveillance, but developments in the understanding of the tumor microenvironment and how the immune system can be re-activated in tumors have had significant clinical impact. Commercially available and experimental methods such as adoptive cellular therapy, cytokine stimulation, and immune checkpoint blockade are promising immunotherapies for a variety of cancers, including solid tumors and hematological malignancies. However, induction of persistent, long-term anti-tumor immunity after initial treatment is infamously difficult. as a result, scientists are searching for new approaches to improve established immunotherapies. by employing combination treatments or enhancing the functionality of …

An Assessment Of Pet Dose Reduction With Penalized Likelihood Image Reconstruction Using A Computationally Efficient Model Observer, Howard C. Gifford, C. Ross Schmidtlein, Andrzej Krol, Yuesheng Xu

Mathematics & Statistics Faculty Publications

Developing PET reconstruction algorithms with improved low-count capabilities may provide a timely and cost- effective means of reducing radiation dose in promising clinical applications such as immuno-PET that require long-lived radiotracers. For many PET clinics, the reconstruction protocol consists of postsmoothed ordered-sets expectation-maximization (OSEM) reconstruction, but penalized likelihood methods based on total-variation (TV) regularization could substantially reduce dose. We performed a task-based comparison of postsmoothed OSEM and higher-order TV (HOTV) reconstructions using simulated images of a contrast-detail phantom. An anthropomorphic visual-search model observer read the images in a location-known receiver operating characteristic (ROC) format. Acquisition counts, target uptake, and target …

In Vitro And In Vivio Evaluation Of A Moisture Treatment Cream Containing Three Critical Elements Of Natural Skin Moisturization, David H. Mcdaniel, Jeffrey S. Dover, Mitchell Wortzman, Diane B. Nelson

Biological Sciences Faculty Publications

Objectives

To evaluate skin barrier and hydration effects of a new rebalancing moisture treatment (TRMT) and to assess efficacy and tolerability in subjects with photodamaged skin.

Methods

In an epidermal skin model, tissues (n = 5/group) were topically treated with 25 µL of TRMT, 25 µL of a market‐leading moisturizer (MLM), or untreated for 60 minutes. Hydration was measured at 0, 15, and 30 minutes. Tissues were harvested for gene expression analysis of markers associated with skin barrier and hydration: Claudin (CLD), Aquaporin (AQP), Hyaluronic Acid Syntheses (HAS), and Hyaluronidase (HYAL). A clinical study evaluated twice‐daily application of TRMT, assessing …

Statistical Analysis Of Fnirs Data: Consideration Of Spatial Varying Coefficient Model Of Prefrontal Cortex Activity Changes During Speech Motor Learning In Apraxia Of Speech, Rachel Johnson, Jennifer Matthews, Norou Diawara, Rachel Carroll

Communication Disorders & Special Education Faculty Publications

Apraxia of speech is an impairment in the planning and programming of speech typically accompanied by aphasia (language impairment) secondary to a left hemisphere stroke. It is unknown if the structural and functional connections to the damaged area implicate the integrity of the cognitive functions of the prefrontal cortex (PFC). The present study examines the feasibility of measuring hemodynamic activity in the PFC in response to the structure of practice and during treatment. This multiple-baseline single case-design study involving two individuals with chronic acquired apraxia of speech measured the hemodynamic changes in PFC activity during treatment across the intervention period …

Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.

First, we generated a novel transgenic animal using the epithelial-specific …

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Molecular Features, Epidemiological Risk Factors, And Evidence-Based Clinical Recommendations, Ryan Decoster

Theses and Dissertations--Clinical and Translational Science

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer of the immune system that can form around textured-surface breast implants. In this dissertation, the cellular and molecular mechanisms of BIA-ALCL are reviewed with a focus on the role of oncogenic JAK-STAT3 signaling in BIA-ALCL tumorigenesis and progression. Herein, the epidemiology of BIA-ALCL is systematically studied to better define the risk of BIA-ALCL and to determine the oncologic safety of smooth surface devices relative to BIA-ALCL formation. Next, a systematic review is conducted which critically appraises current clinical guidelines in order to establish an evidence base to better inform …

Donor Age Effects On The Proliferative And Chondrogenic/Osteogenic Differentiation Performance Of Equine Bone Marrow- And Adipose Tissue Derived Mesenchymal Stem Cells In Culture, Jasmin Bagge

Theses and Dissertations--Veterinary Science

Orthopedic injuries are a major cause of lameness and morbidity in horses. Bone marrow (BM)- and adipose tissue (AT) derived mesenchymal stem cells (MSCs) have shown potential to facilitate the repair of orthopedic injuries and are being used increasingly in veterinary clinics. Presently, the use of MSCs as a therapy for equine patients is most commonly applied as autologous transplants, using BM- and AT-MSCs harvested from the patient shortly after the time of injury. Cell-based therapies are therefore delayed to enable primary cell numbers to be expanded in culture. Of concern, however, are human and rodent studies that have shown …

Comparative Chondrogenesis Of Interzone And Anlagen Cells In Equine Skeletal Development, Chanhee Mok

Theses and Dissertations--Veterinary Science

At the presumptive sites of future synovial joints during mammalian skeletogenesis, articular cartilage develops from interzone located between the cartilaginous anlagen of bones. Thus, two types of cartilaginous tissues differentiate in close proximity. While anlagen cartilage is transient, progressing through endochondral ossification to form bones, articular cartilage is stable and functions throughout life to facilitate both low friction movement and load distribution. Despite important life-long functional properties, articular cartilage has a very limited intrinsic ability to repair structural defects. On the other hand, structural lesions in bones generally heal well by forming a cartilaginous callus and recapitulating endochondral ossification to …

Electrochemical Detection Of Neurotransmitters, Saikat Banerjee, Stephanie Mccracken, Md Faruk Hossain, Gymama Slaughter

Bioelectrics Publications

Neurotransmitters are important chemical messengers in the nervous system that play a crucial role in physiological and physical health. Abnormal levels of neurotransmitters have been correlated with physical, psychotic, and neurodegenerative diseases such as Alzheimer's, Parkinson's, dementia, addiction, depression, and schizophrenia. Although multiple neurotechnological approaches have been reported in the literature, the detection and monitoring of neurotransmitters in the brain remains a challenge and continues to garner significant attention. Neurotechnology that provides high-throughput, as well as fast and specific quantification of target analytes in the brain, without negatively impacting the implanted region is highly desired for the monitoring of the …

Malignant Insulinoma With Multiple Liver Metastases And Hypercalcitoninemia In A Patient With Type 2 Diabetes Mellitus Presenting As Recurrent Episodes Of Diaphoresis Due To Severe Hypoglycemia, Marco Ciacciarelli, Gianluca Caruso, Marco Rengo, Piero Maceroni, Carmen Misurale, Eleonora D'Armiento, Cristina Napoli, Alberto Lombardini, Umberto Ceratti, Ruben Manuel Luciano Colunga Biancatelli, Leonardo Calvosa, Romina Milanese, Sonia Ferri, Teresa Massaro, Andrea Larusso, Veronica Sorrentino, Vincenzo Petrozza

Bioelectrics Publications

Insulinoma is an insulin-producing pancreatic neuroendocrine tumor that can be malignant in about 10% of cases. Locoregional invasion, lymph node metastases, or remote metastases are the main criteria of malignant insulinoma. Its incidence in patients with pre-existing diabetes mellitus (DM) is exceptionally rare. In this report, we describe a 66-year-old man with long-standing type 2 DM who presented with recurrent episodes of diaphoresis due to severe hypoglycemia despite the withdrawal of insulin therapy, hypercalcitoninemia, and biochemical and radiological findings suggestive of metastatic malignant insulinoma. Unfortunately, after few days of diazoxide treatment, edema, hypotension, oliguria, and water retention were observed, patient’s …

Breast Cancer Recurrence Rate In Patients Treated For Early Breast Cancer, Cecilia Munguti

Master of Medicine in General Surgery

Background: Breast cancer, the leading cause of cancer in Kenya among women, has a prevalence of 57.1 per 100,000 women and an annual mortality of 3.7 per 100,000. Early breast cancer is curable, but has a residual risk of recurrence of 10.4% in the first 5 years. Fifty percent of the recurrences occur after the first 5 years after diagnosis. Recurrent breast cancer is associated with poorer prognosis and higher mortality rates. Objectives: The primary objective was to determine the breast cancer recurrence rates for women managed for DCIS and early breast cancer at Aga Khan University Hospital. Secondary objectives …

The Efficacy Of Adding Eicosapentaenoic Acid To Statin Monotherapy In The Prevention Of Acute Coronary Syndrome In Patients With Coronary Artery Disease, Carlo Escudero

Capstone Showcase

Introduction: Coronary artery disease (CAD) is a chronic medical condition caused by the buildup of plaque within the coronary artery endothelium. If left untreated it can progress to an acute coronary syndrome (ACS) which can lead to myocardial ischemia and death. Statins are lipid lowering agents used in clinical practice for the medical management of CAD. However, incidence of major adverse cardiovascular (CV) events still occurs despite optimal statin therapy. Currently eicosapentaenoic acid (EPA) has been promoted to be effective when added to statin therapy in lowering the incidence of CV events in patients with hypercholesterolemia. This paper will address …

Effect Of Epinephrine On Outcomes In Out-Of-Hospital Cardiac Arrest, Ian Lumsden

Capstone Showcase

Abstract

Introduction

Epinephrine administration during cardiac arrest has been the standard of care for decades. In the United States, epinephrine administration has been recommended by the American Heart Association since the first cardiac arrest guidelines were published in 1974. However, epinephrine use became the standard of care with strong medical rational but with limited data on outcomes. The intent of this research is to review available literature and determine if in (P) an adult population in non-traumatic out-of-hospital cardiac arrest (I) treatment with epinephrine administration (C) compared to cardiac care without the administration of epinephrine (O) results in improved survival …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Oxidative Stress Analysis Of Placental Tissue In The Rupp Pregnant Rat, Natalie Ganios

Williams Honors College, Honors Research Projects

Preeclampsia is a disease associated with a vasoconstrictive phenotype due to disrupted signaling in the vascular endothelial growth factor (VEGF) relaxation pathway. The purpose of these studies is to determine the level of oxidative damage that is occurring in the placenta of the reduced uterine perfusion pressure (RUPP) rat, which serves as a common model for preeclampsia. RUPP and SHAM placenta tissue will be examined for oxidative stress as an indicator of tissue damage associated with the pathologically induced ischemia. Oxidative stress in the placental tissue will be measured by performing the following oxidative stress assays: 8-isoprostane test, TBARS assay, …

Modulation Of Epileptogenesis: A Paradigm For The Integration Of Enzyme-Based Microelectrode Arrays And Optogenetics, Corwin R. Butler, Jeffery A. Boychuk, Francois Pomerleau, Ramona Alcala, Peter Huettl, Yi Ai, Johan Jakobsson, Sidney W. Whiteheart, Greg A. Gerhardt, Bret N. Smith, John T. Slevin

Physiology Faculty Publications

BACKGROUND: Genesis of acquired epilepsy includes transformations spanning genetic-to- network-level modifications, disrupting the regional excitatory/inhibitory balance. Methodology concurrently tracking changes at multiple levels is lacking. Here, viral vectors are used to differentially express two opsin proteins in neuronal populations within dentate gyrus (DG) of hippocampus. When activated, these opsins induced excitatory or inhibitory neural output that differentially affected neural networks and epileptogenesis. In vivo measures included behavioral observation coupled to real-time measures of regional glutamate flux using ceramic-based amperometric microelectrode arrays (MEAs).

RESULTS: Using MEA technology, phasic increases of extracellular glutamate were recorded immediately upon application of blue light/488 nm …

Occult Hepatitis B Virus Infection In A Cohort Of Hiv Infected Antiretroviral Therapy Naïve Adults, Adil Suleiman Salyani

Master of Medicine in Internal Medicine

Background: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are endemic to sub-Saharan Africa (SSA) with co-infection being common. Infection with HIV is a risk factor for occult hepatitis B virus infection (OBI), defined as presence of HBV deoxyribonucleic acid (DNA) in the absence of hepatitis B surface antigen (HBsAg). Occult hepatitis B virus infection is further classified based on HBV DNA level as true (/mL) or false (≥200 IU/mL). Presence of OBI is associated with development of liver cirrhosis and hepatocellular carcinoma (HCC). Objectives: The primary outcome was to determine the prevalence of OBI in anti-retroviral therapy (ART) …

Discordance Between Breast Imaging And Histopathology Findings After Ultrasound Guided Core Needle Biopsy, Margaret Mutinda Mwania

Master of Medicine in Imaging and Diagnostic Radiology

Introduction: Breast cancer is the most prevalent cancer among women worldwide with an estimated global incidence of 11.6%. According to the GLOBOCAN factsheet, in 2018 breast cancer incidence in Kenya was 40.3 per 100,000. Early detection and diagnosis of breast cancer has been shown to reduce mortality and increase years of life gained. Breast lesion diagnosis is heavily based on imaging and pathology and typically findings are reported independent of one another. Correlation of imaging findings and pathology after biopsy is found to be of critical importance in detecting possible sampling error, concordance versus discordance, recommend appropriate management and thus …