Medicine and Health Sciences Commons^™

Cognitive, Psychiatric, And Neuropathological Manifestations Of Repetitive Mild Traumatic Brain Injury, Denise Briggs

Wayne State University Dissertations

Millions of athletes participate in contact sports that involve repeated head impacts (e.g., football, ice hockey, boxing), often from a very young age, and it is feared that subsequent impacts can synergize with previous ones so that their effects on the brain become magnified. Repetitive mild traumatic brain injury (rmTBI) has been linked to the development of chronic traumatic encephalopathy (CTE). The neurodegeneration accompanying CTE occurs over many years following repeated head impacts and is characterized by progressive brain atrophy, accumulation of hyper-phosphorylated tau and aggregates of TDP-43, myelinated axonopathy, neuroinflammation and degeneration of white matter tracts. The relationship between …

An Analysis Of Virtual Place Learning/Navigation In Children And Young Adults Prenatally Exposed To Alcohol, Neil Christopher Dodge

Wayne State University Dissertations

Fetal alcohol spectrum disorder refers to the spectrum of disorders resulting from prenatal alcohol exposure and is the leading cause of preventable mental retardation. Rodent studies have found that prenatal alcohol exposure impairs performance on the Morris water maze. This task requires the rodent to use distal room cues to locate a hidden platform in a pool of opaque water. Successful performance on this task is dependent upon hippocampal function. Rodents prenatally exposed to alcohol are impaired on the Morris water maze and show damage to hippocampal neurons. A human analogue of the Morris water maze, the virtual water maze …

Childhood Trauma And Emotion Processing Neurocircuitry, Hilary A. Marusak

Wayne State University Dissertations

Childhood trauma is one of the strongest risk factors for a range of common and debilitating neuropsychiatric disorders, including anxiety, depression, and posttraumatic stress disorder (PTSD). These emotion-related disorders have their roots in childhood and adolescence, underscoring a critical need to understand their biological bases in early life. In this dissertation, we evaluate how childhood trauma impacts emotion processing neurocircuitry in a sample of high-risk urban youth, ages 7-15. In four inter-related studies, we test neural function and functional connectivity of core emotion processing regions, including the amygdala, insula, and pregenual/subgenual anterior cingulate cortex (pgACC/sgACC). To examine the relevance of …

Identification Of Metabolite Biomarkers In Epilepsy Using 1h Mrs, Helen Wu

Wayne State University Dissertations

Epilepsy is a serious neurological disorder that affects 1% percent of the global population. Despite its status as one of the oldest neurological disorders known to man, its mechanisms remain poorly understood. Available medications are not curative but provide symptomatic management and do not work for well for more than 30 percent of patients. Because it is nearly impossible to predict on an individual level who will eventually develop epilepsy, it is also a disorder that can only be diagnosed after the patient has experienced established seizure activity, eliminating any possibility of stopping the disorder in its prodromal phase, before …

Effects Of 7-Day Repeated Treatment With The 5-Ht2a Inverse Agonist/Antagonist Pimavanserin On Methamphetamine Vs. Food Choice In Male Rhesus Monkeys, Matthew L. Banks L. Banks

Pharmacology and Toxicology Publications

Background

Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)_2A receptors modulate mesolimbic dopamine function, such that 5-HT_2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT_2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT_2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys.

Methods …

Identification Of The Metabolic Enzyme Involved Morusin Metabolism And Characterization Of Its Metabolites By Ultraperformance Liquid Chromatogaphy Quadrupole Time-Of-Flight Mass Spectrometry (Uplc/Q-Tof-Ms/Ms), Xianbao Shi, Brianna Mackie, Gang Zhang, Shuman Yang, Yonggui Song, Dan Su, Yali Liu, Lina Shan

Pharmacology and Toxicology Publications

Morusin, the important active component of a traditional Chinese medicine, Morus alba L., has been shown to exhibit many vital pharmacological activities. In this study, six recombinant CYP450 supersomes and liver microsomes were used to perform metabolic studies. Chemical inhibition studies and screening assays with recombinant human cytochrome P450s were also used to characterize the CYP450 isoforms involved in morusin metabolism. The morusin metabolites identified varied greatly among different species. Eight metabolites of morusin were detected in the liver microsomes from pigs (PLMs), rats (RLMs), and monkeys (MLMs) by LC-MS/MS and six metabolites were detected in the liver microsomes from …

Initial Development Of A Patient-Reported Instrument Assessing Harm, Efficacy, And Misuse Of Long-Term Opioid Therapy, William C. Becker, David A. Fiellin, Anne C. Black, Carol T. Kostovich, Robert D. Kerns, Liana Fraenkel

Nursing: School of Nursing Faculty Publications and Other Works

Guidelines on long-term opioid therapy recommend frequent reassessment of harm, efficacy, and misuse of these potentially harmful and sometimes ineffective medications. In primary care, there is a need for a brief, patient-reported instrument. This report details the initial steps in the development of such an instrument. An interdisciplinary team of clinician-scientists performed four discrete steps in this study: (1) conceptualization of the purpose and function of the instrument, (2) assembly of an item pool, (3) expert rating on which items were most important to include in the instrument, and (4) modification of expert-selected items based on a reading level check …

A Urinary Metabolic Signature For Multiple Sclerosis And Neuromyelitis Optica, Teklab Gebregiworgis, Helle H. Nielsen, Chandirasegara Massilamany, Arunakumar Gangaplara, Jay Reddy, Zsolt Illes, Robert Powers

Jay Reddy Publications

Urine is a metabolite-rich biofluid that reflects the body’s effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum …

Metataxonomic And Metagenomic Approaches Vs. Culture-Based Techniques For Clinical Pathology., Sarah K. Hilton, Eduardo Castro-Nallar, Marcos Pérez-Losada, Ian Toma, Timothy A. Mccaffrey, Eric P. Hoffman, Marc O. Siegel, Gary L. Simon, W. Evan Johnson, Keith Crandall

Genomics and Precision Medicine Faculty Publications

Diagnoses that are both timely and accurate are critically important for patients with life-threatening or drug resistant infections. Technological improvements in High-Throughput Sequencing (HTS) have led to its use in pathogen detection and its application in clinical diagnoses of infectious diseases. The present study compares two HTS methods, 16S rRNA marker gene sequencing (metataxonomics) and whole metagenomic shotgun sequencing (metagenomics), in their respective abilities to match the same diagnosis as traditional culture methods (culture inference) for patients with ventilator associated pneumonia (VAP). The metagenomic analysis was able to produce the same diagnosis as culture methods at the species-level for five …

Human Herpesvirus Multiplex Ddpcr Detection In Brain Tissue From Low- And High-Grade Astrocytoma Cases And Controls., Cheng-Te Major Lin, Emily C. Leibovitch, M. Isabel Almira-Suarez, Steven Jacobson

Pathology Faculty Publications

BACKGROUND: Glioblastoma (GBM) is a fatal CNS malignancy, representing 50 % of all gliomas with approximately 12-18 months survival time after initial diagnosis. Recently, the human herpesvirus cytomegalovirus (CMV) has been suggested to have an oncogenic role, yet this association remains controversial. In addition, human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have also been associated with low-grade gliomas, but few studies have examined HHV-6 and EBV in glioblastomas. Droplet digital PCR (ddPCR) is a highly precise diagnostic tool that enables the absolute quantification of target DNA. This study examines the association between multiple human herpesviruses and astrocytomas.

METHODS: This …

The Synergistic Roles Of Cholecystokinin B And Dopamine D5 Receptors On The Regulation Of Renal Sodium Excretion., Xiaoliang Jiang, Wei Chen, Xing Liu, Zihao Wang, Yunpeng Liu, Robin A Felder, John J Gildea, Pedro A. Jose, Chuan Qin, Zhiwei Yang

Medicine Faculty Publications

Renal dopamine D1-like receptors (D1R and D5R) and the gastrin receptor (CCKBR) are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT) cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other's expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was …

Micrornas Are Involved In The Development Of Morphine-Induced Analgesic Tolerance And Regulate Functionally Relevant Changes In Serpini1., Jenica D. Tapocik, Kristin Ceniccola, Cheryl L. Mayo, Melanie L. Schwandt, Matthew Solomon, Bi-Dar Wang, Truong V. Luu, Jacqueline Olender, Thomas Harrigan, Thomas M. Maynard, Greg I. Elmer, Norman H. Lee

Pharmacology and Physiology Faculty Publications

Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The …

Active Stiffening Of F-Actin Network Dominated By Structural Transition Of Actin Filaments Into Bundles, Shengmao Lin, Xinwei Han, Gary C.P. Tsui, David Hui, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

Molecular motor regulated active contractile force is key for cells sensing and responding to their mechanical environment, which leads to characteristic structures and functions of cells. The F-actin network demonstrates a two-order of magnitude increase in its modulus due to contractility; however, the mechanism for this active stiffening remains unclear. Two widely acknowledged hypotheses are that active stiffening of F-actin network is caused by (1) the nonlinear force-extension behavior of cross-linkers, and (2) the loading mode being switched from bending to stretching dominated regime. Direct evidence supporting either theory is lacking. Here we examined these hypotheses and showed that a …

Novel Role Of Cd47 In Obesity-Associated Metabolic Dysfunctions, Heather L. Norman-Burgdolf

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity and its associated comorbidities are of global concern. These complications are largely driven by perturbations in energy homeostasis, inflammation, and oxidative stress within metabolic tissues. Although these underlying pathways have been established, molecular mechanisms augmenting metabolic dysfunction have not been fully defined. CD47, a ubiquitously expressed cell membrane receptor, has been previously implicated in the development of inflammation and oxidative stress in a number of disease conditions. Previous work from our lab and others has confirmed that the most potent ligand of CD47, TSP1, plays a critical role in facilitating inflammation and metabolic dysfunction in diet-induced obesity. Whether these …

Alterations In Plasma Protein C Activity Levels Following Apheresis Platelet Donation And Whole Blood Donation, Frances Duggan, Kathleen O'Sullivan, Joan P. Power, Michael Healy, William G. Murphy

Department of Biological Sciences Publications

Citrate toxicity from platelet apheresis donation has been extensively reported. Effects include symptomatic adverse reactions, silent prolongation of QTc interval on an electrocardiogram and long-term bone effects. While haemostatic impairment is not of concern in healthy plateletpheresis donors, these donors receive doses of citrate during the procedures that induce significant in vivo anticoagulation. We wished to measure the effects this process has on other markers of haemostatic homeostasis, and, in particular, on protein C activity levels. Protein C binds to its activation complex through divalent cation bridges, and is, therefore, susceptible to inactivation by citrate: an effect on protein C …

Nursing Management And Mirror Therapy For Phantom Limb Pain, Bridget Henry

Honors Undergraduate Theses

Phantom limb pain may occur after the accidental removal or surgical amputation of a limb. Phantom limb pain is the experience of pain in the limb that is no longer present. The clinical management of phantom limb pain is essential in the overall reduction of patient rehabilitation and poor patient outcomes. A patient’s degree of phantom limb pain is influenced by their personal response to loss and pain and can have devastating effects to a person’s social performance, occupational role, family role, relationships, and involvement in activities or hobbies. Like most chronic pain, phantom limb pain decreases the quality of …

The Mixed Lineage Kinase-3 Inhibitor Urmc-099 Improves Therapeutic Outcomes For Long-Acting Antiretroviral Therapy., Gang Zhang, Dongwei Guo, Prasanta Dash, Mariluz Araínga, Jayme Wiederin, Nicole A. Haverland, Jaclyn Knibbe-Hollinger, Andrea Martinez-Skinner, Pawel Ciborowski, Val S. Goodfellow, Tadeusz A. Wysocki, Beata J. Wysocki, Larisa Y. Poluektova, Xin-Ming Liu, Joellyn Mcmillan, Santhi Gorantla, Harris A. Gelbard, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) the mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown to facilitate antiviral responses. Long-acting ritonavir-boosted atazanavir (nanoATV/r) nanoformulations co-administered with URMC-099 reduced viral load and the numbers of HIV-1 infected CD4+ T-cells in lymphoid tissues more than either drug alone in infected humanized NOD/SCID/IL2Rγc-/- mice. The drug effects were associated with sustained ART depots. Proteomics analyses demonstrated that the antiretroviral responses were linked to affected phagolysosomal storage pathways leading to sequestration of nanoATV/r in Rab-associated recycling and late endosomes; sites associated with viral …

A Century Of Morphological Variation In Cyprinidae Fishes, Stephen J. Jacquemin, Mark Pyron

Biological Sciences Faculty Publications

Background

Aquatic habitats have been altered over the past century due to a variety of anthropogenic influences. Ecomorphology is an area of aquatic ecology that can both directly and indirectly assess the effects of habitat alterations on organisms. However, few studies have explored long term trends in morphological variation. Long term changes in morphology can potentially impact niche and ultimately contribute to organismal success and the ecosystem. Therefore, in this study we assessed long term morphological variation with body size, sex, time, and hydrology using museum collections of five species of Cyprinidae (Minnows) from lentic and lotic systems over the …

Vitamin D Clinical Relevance In The Recovery From Traumatic Brain Injury Among The Military Population, Yuisa M. Colón

Honors Undergraduate Theses

Background: Traumatic brain injury (TBI) still remains a difficult disorder to treat. TBI has been associated to chronic neuroinflammation and a high risk for neurodegenerative disorders. Since 2001 between ten to twenty percent of all deployed military members have suffered a combat-related TBI. Nearly twenty to thirty percent of those will experience chronic cognitive, behavioral and somatic symptoms after suffering a TBI.
Methods: The objective of this review is to evaluate current literature examining vitamin D as a neurosteroid with protective properties and its clinical relevance after traumatic brain injury. Vitamin D is known to participate in neurobiological …

Medical Interns', Residents' And Attending Physicians' Attitudes Towards Integrative Medicine And Recommended Treatments For Patients With Psoriasis, Jennifer L. Pacyon

PCOM Psychology Dissertations

Background: Psoriasis is a multifactorial disease that effect approximately 7.5 million Americans. There are a variety of traditional treatments for psoriasis (e.g. topical medications, biologics) that for many, are effective in combating the disease. However, traditional treatments often have aversive side effects and may not be appropriate for every patient (e.g. pregnant women). Additionally, the efficacy of these medications are variable leaving some looking for adjunctive treatment options. There is increasing evidence to support the use of adjunctive treatments for psoriatic patients (e.g. psychotherapy, mindfulness). However, research is variable in regards to medical professionals’ attitudes towards integrative medicine (IM) as …

Structural And Functional Characterization Of Enzymes Of A Novel Group Of Tryptophylquinone Cofactor Containing Oxidases, Esha Sehanobish

Electronic Theses and Dissertations

Protein-derived cofactors are redox and catalytic centers that are generally formed by the posttranslational modifications of one or more amino acids. An important class of these cofactors are the quinones derived from tyrosine and tryptophan. Amongst redox proteins, it has been known till now that oxidases either contain a flavin or a tyrosylquinone cofactor, whereas tryptophylquinone ones are present within the dehydrogenases. In recent times, oxidases from a marine bacterium, Marinomonas mediterranea, have been shown to possess the latter. This study involves the characterization of two such proteins, lysine-?-oxidase (LodA) and glycine oxidase (GoxA). They have been reported to contain …

Turn-Around-Time Improvements For Positive Blood Cultures From Incorporation Of Workflow Modifications, Brent Bobik, Allison F. Goldberg, Md, P. Prior, Amity L. Roberts, Phd, D(Abmm)

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Background:

Emergence of direct from positive blood culture bottle identification (ID) methods reveal opportunities for improving bacterial ID and select resistance marker detection turn-around-times. Each system has various advantages and disadvantages; each institution must select the method/s that best fit the laboratory and patient needs. Here we elucidate improvements in 24 hour workflow through incorporating multiple rapid technologies for positive blood culture ID into a 24 hour algorithm.

Methods:

MALDI-TOF (Bruker) analysis with sepsityper extraction (aerobic Gram-positive and anaerobic bacteria); MALDI-TOF analysis with serum separator tube concentration (Gram-negative bacteria); and a FilmArray Blood Culture Panel (Biofire) were utilized. MALDI was …

Pharmacogenomic Management Of Familial Hypercholesterolemia: An Integrative Review Of The Literature, Brian V. Skibo

Honors Undergraduate Theses

The purpose of this thesis is to examine familial hypercholesterolemia (FH) and emerging pharmacogenomics therapies that propose to lower serum low density lipid (LDL) levels. The search of various data bases resulted in nine research articles being selected for review. Syntheses of the articles suggest emerging phamacogenomic drug therapy can improve treatment outcomes for individuals with a diagnosis of FH. The Human Genome Project (HGP) has had far reaching applications for genomic technologies and pharmacagenomic interventions, tailored to human conditions associated with select genomic traits. Synthesis of nine research articles demonstrate that little is known on the topic and reveals …

Expression Levels Of Virulence Genes In Group A Streptococci: A Response To Aerosolized Propylene Glycol, Michael S. Costello

Honors Undergraduate Theses

Electronic cigarette usage is becoming increasingly prevalent among school age children and young adults. A known bactericidal agent, propylene glycol, is often used as a carrier for nicotine, flavoring, and additional constituents of electronic cigarette juice. This study examined the relationship between propylene glycol and virulence gene expression in Streptococcus pyogenes, a respiratory tract pathogen commonly found in school-age individuals. A variety of virulence genes controlled by the three stand alone regulators mga, RofA, and Rgg/RopB were sampled in an effort to understand the pathway by which virulence is affected. The genes chosen encode C5a peptidase, fibronectin binding protein, hyaluronate …

Chronic Pancreatitis, Pain, And Anxiety In An Alcohol And High Fat Mouse Model, Tiffanie Clinkinbeard

Theses and Dissertations--Gerontology

Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP.

In …

Molecular Genetics Of Ms4a6a And Alzheimer's Disease, Ryan Harpole

Lewis Honors College Capstone Collection

Increased Alzheimer’s disease (AD) risk has previously been associated with a SNP called rs610932 near the gene MS4A6A. The goal of this experiment was to quantify the expression of two MS4A6A isoforms in the brains of AD and non-AD subjects, particularly as a function of rs610932 genotype. According to an article titled “Alzheimer’s Disease Susceptibility Variants in the MS4A6A Gene are Associated with Altered Levels of MS4A6A Expression in Blood”, MS4A6A has four different isoforms that have been reported to be differentially expressed in the blood of AD subjects compared to non-AD subjects (Petroula et al., 2014). After statistically …

Limited Trabecular Bone Density Heterogeneity In The Human Skeleton, Habiba Chirchir Phd

Biological Sciences Faculty Research

There is evidence for variation in trabecular bone density and volume within an individual skeleton, albeit in a few anatomical sites, which is partly dependent on mechanical loading. However, little is known regarding the basic variation in trabecular bone density throughout the skeleton in healthy human adults. This is because research on bone density has been confined to a few skeletal elements, which can be readily measured using available imaging technology particularly in clinical settings. This study comprehensively investigates the distribution of trabecular bone density within the human skeleton in nine skeletal sites (femur, proximal and distal tibia, third metatarsal, …

Capillary Endothelia From Two Adpkd Patients Are Polyploidy, Sarmed H. Kathem, Wissam A. Aboualaiwi, Xiaolin Zi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Bilateral renal cyst formation is the main feature of autosomal dominant polycystic kidney disease (ADPKD). We and other laboratories have previously shown that cystlining epithelia of kidneys from ADPKD patients are characterized by polyploidy. In this report, we show that endothelia from the renal capillary beds of two ADPKD patients are also polyploidy. Spectral karyotyping study further confirms our flow cytometry analyses. We suggest that polyploidy may be used as a potential cellular marker in ADPKD.

Therapy Options For Winged Scapula Patients: A Literature Review, Samantha L. Normand

Honors Undergraduate Theses

Winged scapula is a condition characterized by lateral or medial protrusion of the scapula caused by nerve damage leading to muscular paralysis. The purpose of this systematic review of literature is to evaluate the current research literature related to the effectiveness of therapy options for winged scapula. Eleven peer reviewed English language research articles published from 1998 to present were included for evaluation. Study results revealed positive therapeutic outcomes for physical therapy and scapular bracing. Results also showed positive outcomes for the use of transcutaneous electrical nerve stimulation and acupuncture for the treatment of nerve related conditions similar to winged …

Giant Chloroviruses: Five Easy Questions, James L. Van Etten, David Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large, icosahedral, dsDNA-containing viruses that replicate in certain unicellular, chlorella-like green algae [1,2]. They exist in freshwater throughout the world with titers as high as thousands of plaque-forming units (PFU) per ml of indigenous water although titers are typically 1–100 PFU/ml. Titers fluctuate during the year with the highest titers typically occurring in the spring and late fall. Known chlorovirus hosts, which are normally symbionts and are often referred to as zoochlorellae, are associated with either the protozoan Paramecium bursaria (Fig 1A), the coelenterate Hydra viridis, or the heliozoan Acanthocystis turfacea. Zoochlorellae are resistant to viruses …