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Translating Intracarotid Artery Transplantation Of Bone Marrow-Derived Ncs-01 Cells For Ischemic Stroke: Behavioral And Histological Readouts And Mechanistic Insights Into Stem Cell Therapy, Yuji Kaneko, Jea-Young Lee, Naoki Tajiri, Julian P. Tuazon, Trenton Lippert, Eleonora Russo, Seong-Jin Yu, Brooke Bonsack, Sydney Corey, Alexandreya B. Coats, Chase Kingsbury, Thomas N. Chase, Minako Koga, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

The present study used in vitro and in vivo stroke models to demonstrate the safety, efficacy, and mechanism of action of adult human bone marrow-derived NCS-01 cells. Coculture with NCS-01 cells protected primary rat cortical cells or human neural progenitor cells from oxygen glucose deprivation. Adult rats that were subjected to middle cerebral artery occlusion, transiently or permanently, and subsequently received intracarotid artery or intravenous transplants of NCS-01 cells displayed dose-dependent improvements in motor and neurological behaviors, and reductions in infarct area and peri-infarct cell loss, much better than intravenous administration. The optimal dose was 7.5 × 106 cells/mL when …

Early Acid/Base And Electrolyte Changes In Permanent Middle Cerebral Artery Occlusion: Aged Male And Female Rats, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Sarah J. Goodwin, David Powell, Doug Lukins, Justin F. Fraser, Keith R. Pennypacker

Neurosurgery Faculty Publications

BACKGROUND: Early changes in acid/base and electrolyte concentrations could provide insights into the development of neuropathology at the onset of stroke. We evaluated associations between acid/base and electrolyte concentrations, and outcomes in permanent middle cerebral artery occlusion (pMCAO) model.

METHODS: 18-month-old male and female Sprague-Dawley rats underwent pMCAO. Pre-, post- (7 min after occlusion), and at 72 hr of pMCAO venous blood samples provided pH, carbon dioxide, oxygen, glucose, hematocrit, hemoglobin, and electrolyte values of ionized calcium, potassium, and sodium. Multiple linear regression determined predictors of infarct and edema volumes from these values, Kaplan-Meier curve analyzed morality between males and …

The Use Of Yank-Time Signal As An Alternative To Identify Kinematic Events And Define Phases In Human Countermovement Jumping, Sofyan Sahrom, Jodie C. Wilkie, Kazunori Nosaka, Anthony J. Blazevich

Research outputs 2014 to 2021

Detailed examinations of both the movement and muscle activation patterns used by animals and humans to complete complex tasks are difficult to obtain in many environments. Therefore, the ability to infer movement and muscle activation patterns after capture of a single set of easily obtained data is highly sought after. One possible solution to this problem is to capture force-time data through the use of appropriate transducers, then interrogate the signal's derivative, the yank-time signal, which amplifies, and thus highlights, temporal force-time changes. Because the countermovement vertical jump (CMJ) is a complex movement that has been well studied in humans, …

The Role Of Interleukin-18 In Myocardial Ischemia/Reperfusion, Yogesh Dhakal

Theses and Dissertations

Acute Myocardial Infarction (AMI) is one of the leading causes of morbidity for cardiovascular diseases (CVDs) in the western world. While mortality rates for AMI has reduced in the last 20 years due to advancements in clinical interventions, patients who have an AMI are significantly more likely to develop heart failure (HF) in the following years. Reperfusion of the ischemic tissue is a necessary procedure to restore blood delivery to cardiomyocytes, minimize myocardial dysfunction, and reduce infarct size. Still, the step of reperfusion itself induces myocardial damage in a phenomenon known as reperfusion injury. Considering that the degree of myocardial …

Serum 25-Hydroxyvitamin D Levels In Children With Mild And Severe Atopic Asthma, Rhoda Ndinda Masaku

Master of Medicine in Paediatrics and Child Health

Background: Asthma is a chronic respiratory illness affecting an estimated 334 million people worldwide, including 14% of the total pediatric population. It results in significant morbidity, and therefore the etiologies and risk factors associated with asthma are of great interest. Serum 25- hydroxyvitamin D (25(OH)D) has substantial immunomodulatory effects on the innate immune system. It reduces the probability of viral respiratory infections and asthma exacerbations by potentiating the anti-inflammatory action of corticosteroids. Objectives: This study was conducted to determine if there was a difference in serum 25-hydroxyvitamin D levels between children with mild and severe atopic asthma and explored the …

Spatially Fractionated Radiation Therapy: History, Present And The Future, Weisi Yan, Mohammad K. Khan, Xiaodong Wu, Charles B. Simone Ii, Jiajin Fan, Eric Gressen, Xin Zhang, Charles L. Limoli, Houda Bahig, Slavisa Tubin, Waleed F. Mourad

Department of Radiation Oncology Faculty Papers

No abstract provided.

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 …

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. …

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 …

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 …

Recent Advances On Visual Cycle Protein Research And Progress On Clinical Translation, Xin Yee Ooi, Rujman Khan, Anjalee Choudhury, Francisco Xavier Elisarraras, Jeff Grigsby, Brandi Obregon, Andrew T C Tsin

School of Medicine Publications

Since the publication of our previous paper, Visual cycle proteins: Structure, function, and roles in human retinal disease (Tsin, et.al, JBC 293:13016, 2018) there has been significant progress on multiple topics discussed in this paper. In the present communication, we further explore research advances on two visual cycle proteins: DES1 and IRBP. In addition, we emphasize the progress of clinical translation of other visual cycle protein research, including the breakthrough of FDA-approved gene therapy for Leber’s congenital amaurosis, and additional gene therapies at different stages of clinical trials for various retinal diseases such as retinitis pigmentosa, diabetic retinopathy, and Stargardt’s …

Sirt3 Promotes Lipophagy And Chaperon-Mediated Autophagy To Protect Hepatocytes Against Lipotoxicity, Tian Zhang, Jingxin Liu, Shengnan Shen, Qiang Tong, Xiaojun Ma, Ligen Lin

Faculty, Staff and Students Publications

Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD+-dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. …

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …

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 …

Ileal Atresia, Obiyo O. Osuchukwu, Rebecca M. Rentea

Manuscripts, Articles, Book Chapters and Other Papers

Ileal and jejunal atresias are usually described together as jejunoileal atresia (JIA). JIA is a common cause of intestinal obstruction in neonates. It is seen in 1 in 5000 to 1 in 14000 live births. Intestinal atresia can occur in any location on the small bowel as a solitary or even multiple lesions. Distally located atresia usually presents with delayed symptoms compared to proximal ones. Occasionally, JIA is associated with other malformations such as cardiac anomalies, gastroschisis, and cystic fibrosis. Evaluation can be initiated before birth with prenatal diagnosis using ultrasound findings of evidence of intestinal obstruction reported in 29% …

The Effect Of Interventions On Radiotherapy-Induced Skin Toxicity: A Systematic Review, Claudia R. Figueroa

Honors Undergraduate Theses

Various studies show a variety of interventions for radiotherapy-induced skin toxicity. Radiotherapy-induced skin toxicity is the most common side effect for women with breast cancer who undergo radiotherapy sessions. Intervention agents include topical creams, barrier films, oral agents, as well as laser therapy. However, despite the variety of intervention agents available, there is still a lack of accepted guidelines to manage radiotherapy-induced skin toxicity. This thesis aims to conduct a systematic review and meta-analysis of published randomized controlled trials with the primary purpose of exploring the available intervention methods to prevent radiotherapy-induced skin toxicity and evaluate the effects of different …

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 …

Residential Radon Exposure, Its Contribution To Lung Cancer, And Social Determinants Of Radon Testing, Stacy Stanifer

Theses and Dissertations--Nursing

Lung cancer is a highly preventable form of cancer. Cigarette smoking is the leading cause of lung cancer followed by radon gas exposure and exposure to secondhand smoke. Kentucky leads the nation in both incidence and mortality from lung cancer. Tobacco use in Kentucky continues to be a major public health concern as nearly one-quarter of adults report current tobacco use and just over one-third of Kentucky homes with children lack rules which prohibit smoking in the home. Radon, a colorless, odorless radioactive gas, occurs naturally from the decay of uranium found in rocks and soil and is harmful when …

Antiresorptive Bone Therapy Use In Advanced Lung Cancer And Associated Outcomes, Noor Naffakh

Theses and Dissertations--Pharmacy

Background/Rationale: Studies have shown antiresorptive agents decrease skeletal related events in metastatic non-small cell lung cancer. However, two prevalence studies have found low utilization rates of antiresorptive therapy in advanced lung cancer. The first study reported a rate of 14.8% during the 1995-2009 time period, while the second study reported a 33% usage rate during the time frame of 2002-2011. We believe these low utilization rates are associated with the poor prognosis of these patients. The prognosis of advanced lung cancer has improved significantly since these trials were conducted, and the utilization of denosumab has not been evaluated. We hypothesize …

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 …

The Effect Of Haptoglobin Phenotypes On Markers Of Neuroinflammation In Patients With Aneurysmal Subarachnoid Hemorrhage, Kevin Hatton

Theses and Dissertations--Clinical and Translational Science

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of hemorrhagic stroke resulting from the spontaneous rupture of an intracranial aneurysm and release of oxygenated blood into the subarachnoid space. In the United States alone, aSAH occurs in approximately 30,000 patients each year and occurs, primarily, in otherwise healthy adults, frequently without warning. Sadly, approximately 40% of patients with aSAH will die in the first 30 days. Of those who survive, only about 75% will be able to live semi-independently again and only about 60% will be able to return to work.

Delayed brain injuries (DBI), which may affect up to …

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 …

Dynamic Blood-Brain Barrier Regulation In Mild Traumatic Brain Injury, Eoin O'Keeffe, Eoin Kelly, Yuzhe Liu, Chiara Giordano, Eugene Wallace, Mark Hynes, Stephen Tiernan, Aidan Meagher, Chris Greene, Stephanie Hughes, Tom Burke, John Kealy, Niamh Doyle, Alison Hay, Michael Farrell, Gerald A. Grant, Alon Friedman, Ronel Veksler, Michael G. Molloy, James F. Meaney, Niall Pender, David Camarillo, Colin P. Doherty, Matthew Campbell

Articles

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast …

Manipulation Of Ar-V7 In Castrate Resistant Prostate Cancer, Sean Simpson

Capstone Showcase

Abstract

Introduction: Prostate cancer is the leading cancer affecting men of all races in the United States, and the second leading cause of cancer death in men. If caught early, many have had success in combating the disease, but if the cancer metastasizes, the 5-year survival rate drops to only 30%. Current treatment options heavily involve hormone therapy, radiation therapy, chemotherapy, and surgery. While these treatments can be effective for early stage prostate cancer, they can fall short in preventing the spread of the cancer to other parts of the body. This review analyzes a new potential way of preventing …

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 …