Digital Commons Network^™

Possible Causes Of Alzheimer’S Disease Related Amyloid-Β Plaques And Neurofibrillary Tangles, Rochelle Rubenstein

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a major cause of dementia in the elderly and is a global health concern. However, researchers are not sure what causes the characteristic amyloid-β plaque accumulation and neurofibrillary tangles in the brain. Several model mechanisms have been proposed to answer this question. This paper examines three of these possibilities. Research suggests that a particular allele of the apoE gene is responsible for the neurodegeneration found in Alzheimer’s disease. Another hypothesis is that the mechanism of Alzheimer’s is related to prion-mediated protein misfolding. Other studies indicate that certain environmental factors can cause the neuropathology of Alzheimer’s. Specifically, this …

Are Contact Lenses An Effective Vehicle For Ocular-Disease Drug Delivery?, Chana Haimowitz

The Science Journal of the Lander College of Arts and Sciences

Due to numerous drawbacks with current modes of treatment for various ocular diseases, researchers are synthesizing drug dispensing contact lenses. The lenses will contribute to greater bioavailability of the drug, the minimization of negative side effects, and increased patient compliance. As treatment for glaucoma, in vivo studies have been conducted with latanoprost, timolol maleate, and brimonidine tartrate-eluting lenses, and have succeeded in reducing intraocular pressure to desired values (Ciolino et al., 2016), (Schultz and Mint, 2002). As treatment for fungal keratitis, in vitro studies prove that econazole and natamycin-eluting contact lenses have been successful in killing 100% of fungi for …

Repurposing Diabetes Drugs To Treat Insulin Resistance In Alzheimer’S Disease‌, Yael Lazarus

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a neurodegenerative condition which results in a significant decline in cognitive status. Novel treatment approaches for Alzheimer’s are sorely needed, as current medications for the disease offer only marginal clinical benefit. Research has discovered a connection between the pathology of Alzheimer’s and Type 2 Diabetes, two serious and seemingly unrelated disorders. Clinical studies have shown that Alzheimer’s disease is associated with brain insulin resistance similar to the pathology of Type 2 Diabetes. This observation has led to the notion that drugs developed for the treatment of Type 2 Diabetes may be beneficial in modifying the cognitive function …

The Relationship Between Periodontitis And Cardiovascular Disease, Jonathan Krupka

The Science Journal of the Lander College of Arts and Sciences

The relationship between periodontal disease and cardiovascular disease has been the subject of much research in recent years. The aim of this study is to review and analyze the relevant literature regarding this relationship, with an emphasis on determining a presence of periodontal bacteria from the periodontal pocket in atheromatous plaques, and to explore the biological role of inflammatory mechanisms that may link periodontitis and cardiovascular disease. Although there seems to be conflicting reports, the overall consensus confirms the presence of periodontal bacteria, such as Porphyromonas gingivalis, in atheromatous plaques. Additionally, the presence of systemic markers of cardiovascular disease in …

Luteinizing Hormone And Alzheimer’S Disease: Impact And Possibilities Of Treatment, Rachel Walkin

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a common neurodegenerative disease that is the 6th leading cause of death in the United States. An estimated 5 million Americans are afflicted nationwide and the cost to the economy is valued at 259 billion dollars. Additionally, unlike other major causes of death in the United States, there is no treatment for Alzheimer’s Disease. Alzheimer’s is a progressive disease and it is strongly tied to aging. In most cases symptoms make their first appearance in the late 60’s and gradually worsen, eventually leading to a loss of cognitive function and death. The two outstanding changes in the …

Should Genetic Testing Be Recommended For Long Qt Syndrome Patients And Their Relatives?, Menachem Braun

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Bladder Antimuscarinics And Cognitive Decline In Elderly Patients, Daniela Claudia Moga, Erin L. Abner, Qishan Wu, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

Introduction: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent.

Methods: A retrospective analysis of data from the National Alzheimer's Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores.

Results: Our analyses included 698 …

Defining The Risk Of Zika And Chikungunya Virus Transmission In Human Population Centers Of The Eastern United States, Carrie A. Manore, Richard S. Ostfeld, Folashade B. Agusto, Holly Gaff, Shannon L. Ladeau

Biological Sciences Faculty Publications

The recent spread of mosquito-transmitted viruses and associated disease to the Americas motivates a new, data-driven evaluation of risk in temperate population centers. Temperate regions are generally expected to pose low risk for significant mosquito-borne disease; however, the spread of the Asian tiger mosquito (Aedes albopictus) across densely populated urban areas has established a new landscape of risk. We use a model informed by field data to assess the conditions likely to facilitate local transmission of chikungunya and Zika viruses from an infected traveler to Ae. albopictus and then to other humans in USA cities with variable human …

Consequences Of Altered Short-Chain Carbon Metabolism In Heart Failure, Julie Horton

Electronic Theses and Dissertations

Cardiovascular disease is currently the foremost cause of death within the United States. Heart failure (HF) is a syndrome defined by the inability of the heart to adequately execute requisite pump function in order to deliver nutrients and oxygen to peripheral tissues, irrespective of etiology. One of the most common causes of HF is chronic pressure overload due to hypertension. Ischemic heart disease is also a common driver of HF, often in conjunction with hypertension. Pressure overload initially causes compensatory metabolic changes. Structural changes follow shortly thereafter typically resulting in left ventricular hypertrophy. Eventually, the heart loses the ability to …

Remote Sensing Observation Of Annual Dust Cycles And Possible Causality Of Kawasaki Disease Outbreaks In Japan, Hesham El-Askary, Nick Lahaye, Erik J. Linstead, William A. Sprigg, Magdi Yacoub

Mathematics, Physics, and Computer Science Faculty Articles and Research

Kawasaki disease (KD) is a rare vascular disease that, if left untreated, can result in irreparable cardiac damage in children. While the symptoms of KD are well-known, as are best practices for treatment, the etiology of the disease and the factors contributing to KD outbreaks remain puzzling to both medical practitioners and scientists alike. Recently, a fungus known as Candida, originating in the farmlands of China, has been blamed for outbreaks in China and Japan, with the hypothesis that it can be transported over long ranges via different wind mechanisms. This paper provides evidence to understand the transport mechanisms …

Gastrointestinal Bleeding Events And Statin Use: A Large Propensity Score-Matched Retrospective Cohort Study, Ashley I. Martinez

Theses and Dissertations--Pharmacy

Literature is conflicting regarding the association between statin use and gastrointestinal (GI) bleeding. This study sought to determine whether there is an association between statin use and GI bleeding by comparing incidence of gastrointestinal events between statin users and an active comparator group.

Data was obtained from a large administrative claims database composed of subjects enrolled in a selection of insurance plans throughout the United States from 2009-2014. New statin users (exposed) and thyroid medication users (active comparator, unexposed) were followed from the baseline period (one year prior to medication initiation) until first event, discontinuation, or disenrollment. Subjects were matched …

Promotion Of Early Pediatric Hearing Detection Through Patient Navigation, Matthew L. Bush

Theses and Dissertations--Clinical and Translational Science

Congenital hearing loss is the most common neonatal sensory disorder and it is crucial to diagnose hearing loss as soon as possible after birth in order to facilitate rapid treatment. Universal standards of infant hearing healthcare dictate that infant hearing screening should be completed by one month of age and abnormal screening tests should be followed with definitive audiological testing by three months of age. Obtaining diagnostic testing can be complicated by limited access to care in rural areas, breakdowns in communication, lack of parental support, and poor coordination of care. There is no established method to address appointment non-adherence …

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Protection From Aortic Aneurysm By Bmal1 Deletion From Smooth Muscle Cells, Jenny Lutshumba

Theses and Dissertations--Physiology

Abdominal aortic aneurysm (AAA) is a devastating condition that occurs primarily among older people with high mortality when a rupture occurs. Currently there is no proven pharmacological therapy for AAA due to poor understanding of the underlying pathogenesis. The brain and muscle transcription factor ARNT-like (Bmal1), which is known to regulate circadian rhythm, has been implicated in vascular pathologies including atherosclerosis and vascular remodeling, but its role in AAA has not been explored.

Vascular smooth muscle is a central player in aneurysm formation and development because it is critical in all three aortic aneurysm hallmark processes including (a) degradation of …

Neuroinflammation In Alzheimer's Disease And Vascular Cognitive Impairment, Erica M. Weekman

Theses and Dissertations--Physiology

It was once believed that the brain was immunologically privileged with no resident or infiltrating immune cells; however, now it is understood that the cells of the brain are capable of a wide range of inflammatory processes and phenotypes. Inflammation in the brain has been implicated in several disease processes such as Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID); however, the role of inflammation in these two dementias is poorly understood.

When we stimulated a pro-inflammatory phenotype with an adeno-associated viral vector in a transgenic mouse model of AD that develops Aβ plaques, we saw a pro-inflammatory …

New Insights Into Post-Sepsis Muscle Weakness Elucidated Using A Novel Animal Model, Allison M. Steele

Theses and Dissertations--Physiology

Sepsis is a severe life-threatening critical illness that damages multiple physiological systems. After hospital discharge, more than 70% of severe sepsis survivors report profound weakness which significantly impacts quality of life. Such weakness gives rise to new limitations of daily living, which ultimately leads to loss of independence in many patients. Despite wide recognition of this serious issue by clinicians and researchers alike, the mechanisms contributing to chronic skeletal muscle dysfunction after sepsis are not well understood. Lack of progress in this field is largely due to the absence of an appropriate animal model; current models are either too mild …

Analysis Of Humoral Immune Responses In Horses With Equine Protozoal Myeloencephalitis, Catherine-Jane Angwin

Theses and Dissertations--Veterinary Science

Equine protozoal myeloencephalitis (EPM), caused by the protozoan parasite Sarcocystis neurona, is one of the most important neurological diseases of horses in the Americas. While seroprevalence of S. neurona in horses is high, clinical manifestation of EPM occurs in less than 1% of infected horses. Factors governing the occurrence and severity of EPM are largely unknown, although horse immunity might play an important role in clinical outcome. We hypothesize that EPM occurs due to an aberrant immune response, which will be discernable in the equine IgG subisotypes a, b, and (T) that recognize S. neurona in infected diseased horses versus …

Hispanic Use Of Alternative Medicine As Demonstrated In Internet Searches, Elad Yom-Tov, William F. Strong, Lupita Rodriguez Strong

Communication Faculty Publications

Objective: We investigated how cultural shifts occur with respect to the use of traditional medicine for influenza-like illness (ILI) within the Latino population near the US-Mexico border.

Methods: We extracted searches of ILI treatments (modern, traditional western, and traditional Hispanic) to the Bing search engine from 5 US states near the US-Mexico border. The incidence of these searches was correlated with county-level demographic data and ILI incidence.

Results: The fraction of queries related to Hispanic medicines is correlated with the distance from the US-Mexico border (Spearman rho = -0.24), which is a slower decay than that observed in the use …

All-Cause Mortality In Hiv-Positive Adults Starting Combination Antiretroviral Therapy: Correcting For Loss To Follow-Up, Nanina Anderegg, Leigh F. Johnson, Elizabeth Zaniewski, Keri N. Althoff, Eric Balestre, Matthew Law, Denis Nash, Bryan E. Shepherd, Constantin T. Yiannoutsos, Matthias Egger

Publications and Research

Objective: To estimate mortality in HIV-positive patients starting combination antiretroviral therapy (ART) and to discuss different approaches to calculating correction factors to account for loss to follow-up.

Methods: A total of 222 096 adult HIV-positive patients who started ART 2009–2014 in clinics participating in the International epidemiology Databases to Evaluate AIDS collaboration in 43 countries in sub-Saharan Africa, Asia Pacific, Latin America, and North America were included. To allow for underascertainment of deaths due to loss to follow-up, two correction factors (one for the period 0–6 months on ART and one for later periods) or 168 correction factors (combinations of …

Assessing Provider Adherence To The 2013 Acc/Aha Hyperlipidemia Guideline, Adrienne Johnston

DNP Projects

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the United States and accounts for more than 17.3 million deaths per year with hyperlipidemia as one of the leading risk factors. The 2013 American Heart Association/American College of Cardiology (AHA/ACC) hyperlipidemia guideline recommends healthy lifestyle habits, risk estimation of the development of cardiovascular disease using a risk calculator, and intensity dosed statin therapy. There has been controversy among providers resulting in confusion and inconsistent application of the guideline. Purpose: The purpose of this project was to examine provider adherence to the AHA/ACC hyperlipidemia guideline in a primary …

Anti-Inflammatory And Immune-Modulating Effects Of Rice Callus Suspension Culture And Blueberry Extract On An In-Vitro Inflammatory Bowel Disease Model, Kyle Michael Driscoll

Dissertations, Master's Theses and Master's Reports

Rice Callus Suspension Culture (RCSC) has been shown to exhibit potent anticancer activity in vitro. In this study we aimed to investigate the anti-inflammatory and immune-modulating properties of RCSC on three inflamed normal colon epithelial cell lines, InEpC, NCM 356, and CCD 841 CoN. As a comparative, we additionally analyzed the anti-inflammatory effects of Highbush blueberries on two inflamed colon cell cultures, NCM 356 and CCD 841 CoN. Furthermore, we sought to characterize the bioactive compounds in RCSC responsible for anti-cancer, anti-inflammatory, and immune-modulating effects. This work will be an essential starting point for understanding and identifying possible bioactive …

Development And Characterization Of Histidine-Tagged Hpv16 L2 And Ms2-Arginine-Tagged Recombinant Proteins For Downstream Processes, Tahiyat Alothaim

Dissertations, Master's Theses and Master's Reports

Human papillomaviruses (HPVs) are the most common sexually transmitted infections. Persistent infection with HPV can lead to anogenital cancers including head and neck cancers. Three prophylactic vaccines have been approved to prevent against some types of HPV infection. However, the vaccines are HPV-type specific and protect mostly against the HPV types included in the vaccines. To offer broader protection against more HPV types, studies in the field are developing candidate vaccines targeting a conserved minor capsid protein, L2. Nevertheless, reagents for developing and assessing L2 vaccines are limited. For example, antibodies to assess the antigenicity of some L2 epitopes are …

Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski

Sanders-Brown Center on Aging Faculty Publications

Background

Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies.

Methods

In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of …

Ligand Trap Of The Activin Receptor Type Iia Inhibits Osteoclast Stimulation Of Bone Remodeling In Diabetic Mice With Chronic Kidney Disease, Toshifumi Sugatani, Olga A. Agapova, Yifu Fang, Alycia G. Berman, Joseph M. Wallace, Hartmut H. Malluche, Marie-Claude Faugere, William Smith, Victoria Sung, Keith A. Hruska

Internal Medicine Faculty Publications

Dysregulation of skeletal remodeling is a component of renal osteodystrophy. Previously, we showed that activin receptor signaling is differentially affected in various tissues in chronic kidney disease (CKD). We tested whether a ligand trap for the activin receptor type 2A (RAP-011) is an effective treatment of the osteodystrophy of the CKD-mineral bone disorder. With a 70% reduction in the glomerular filtration rate, CKD was induced at 14 weeks of age in the ldlr−/− high fat-fed mouse model of atherosclerotic vascular calcification and diabetes. Twenty mice with CKD, hyperphosphatemia, hyperparathyroidism, and elevated activin A were treated with RAP-011, wherease 19 …

Use Of Sex-Specific Clinical And Exercise Risk Scores To Identify Patients At Increased Risk For All-Cause Mortality, Paul C. Cremer, Yuping Wu, Haitham M. Ahmed, Lee M. Pierson, Danielle M. Brennan, Mouaz H. Al-Mallah, Clinton A. Brawner, Jonathan K. Ehrman, Steven J. Keteyian, Roger S. Blumenthal, Michael J. Blaha, Leslie Cho

Mathematics and Statistics Faculty Publications

Importance Risk assessment tools for exercise treadmill testing may have limited external validity. Cardiovascular mortality has decreased in recent decades, and women have been underrepresented in prior cohorts.

Objectives To determine whether exercise and clinical variables are associated with differential mortality outcomes in men and women and to assess whether sex-specific risk scores better estimate all-cause mortality.

Design, Setting, and Participants This retrospective cohort study included 59 877 patients seen at the Cleveland Clinic Foundation (CCF cohort) from January 1, 2000, through December 31, 2010, and 49 278 patients seen at the Henry Ford Hospital (FIT cohort) from January 1, …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …

Human Tear Fluid Reduces Culturability Of Contact Lens-Associated Pseudomonas Aeruginosa Biofilms But Induces Expression Of The Virulence-Associated Type Iii Secretion System, Yvonne T. Wu, Connie Tam, Lucia S. Zhu, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Purpose

The type III secretion system (T3SS) is a significant virulence determinant for Pseudomonas aeruginosa. Using a rodent model, we found that contact lens(CL)-related corneal infections were associated with lens surface biofilms. Here, we studied the impact of human tear fluid on CL-associated biofilm growth and T3SS expression.

Methods

P. aeruginosa biofilms were formed on contact lenses for up to 7 days with or without human tear fluid, then exposed to tear fluid for 5 or 24 h. Biofilms were imaged using confocal microscopy. Bacterial culturability was quantified by viable counts, and T3SS gene expression measured …

Anti-Inflammatory And Neuroprotective Role Of Natural Product Securinine In Activated Glial Cells: Implications For Parkinson’S Disease, Dmitri Leonoudakis, Anand Rane, Suzanne Angeli, Gordon J. Lithgow, Julie K. Andersen, Shankar J. Chinta

Faculty Publications & Research of the TUC College of Pharmacy

Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson’s disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis. In this study, we explored the underlying mechanisms of neuroprotection elicited by securinine, particularly its anti-inflammatory effects …

Steroid Hormone Receptors As Prognostic Markers In Breast Cancer, Maggie C. Louie, Mary B. Sevigny

Faculty Publications & Research of the TUC College of Pharmacy

Despite the existence of many promising anti-cancer therapies, not all breast cancers are equally treatable, due partly to the fact that focus has been primarily on a few select breast cancer biomarkers- notably ERα, PR and HER2. In cases like triple negative breast cancer (ERα-, PR-, and HER2-), there is a complete lack of available biomarkers for prognosis and therapeutic purposes. The goal of this review is to determine if other steroid receptors, like ERβ and AR, could play a prognostic and/or therapeutic role. Data from various in vitro, in vivo, and clinical breast cancer studies were examined …

Single Low-Dose Lipopolysaccharide Preconditioning: Neuroprotective Against Axonal Injury And Modulates Glial Cells, Ryan C. Turner, Zachary J. Naser, Brandon P. Lucke-Wold, Aric F. Logsdon, Reyna L. Vangilder, Rae Reiko Matsumoto, Jason D. Huber

Faculty Publications & Research of the TUC College of Pharmacy

AIM: Over 7 million traumatic brain injuries (TBI) are reported each year in the United States. However, treatments and neuroprotection following TBI are limited because secondary injury cascades are poorly understood. Lipopolysaccharide (LPS) administration before controlled cortical impact can contribute to neuroprotection. However, the underlying mechanisms and whether LPS preconditioning confers neuroprotection against closed-head injuries remains unclear.

METHODS: The authors hypothesized that preconditioning with a low dose of LPS (0.2 mg/kg) would regulate glial reactivity and protect against diffuse axonal injury induced by weight drop. LPS was administered 7 days prior to TBI. LPS administration reduced locomotion, which recovered completely …