Diseases Commons^™

Functional Characteristics Of Four Novel Lone Atrial Fibrillation-Linked Connexin40 Mutants, Mahmoud Noureldin

Electronic Thesis and Dissertation Repository

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Recently, four novel heterozygous Cx40 mutations, K107R, L223M, Q236H, and I257L were identified in 4 of 310 unrelated AF patients. To study possible alterations associated with these mutants, we studied their localization and function using gap junction (GJ)-deficient model cells. Cell pairs expressing Q236H alone or together with wildtype Cx43 showed a significantly lower coupling conductance. Impaired GJ function and dominant negative action on Cx43 of this mutant are consistent with previous findings on the majority of AF-linked Cx40 mutants. The remaining three novel AF-linked mutants did not show …

Pixuna Virus Modifies Host Cell Cytoskeleton To Secure Infection, Pedro Ignacio Gil, Guillermo Albrieu-Llinás, Estela Cecilia Mlewski, Marina Monetti, Laura Fozzatti, Cecilia Cuffini, José Fernández-Romero, Patricia Kunda, María Gabriela Paglini

Publications and Research

Pixuna virus (PIXV) is an enzootic member of the Venezuelan Equine Encephalitis Virus complex and belongs to the New World cluster of alphaviruses. Herein we explore the role of the cellular cytoskeleton during PIXV replication. We first identified that PIXV undergoes an eclipse phase consisting of 4 h followed by 20 h of an exponential phase in Vero cells. The infected cells showed morphological changes due to structural modifications in actin microfilaments (MFs) and microtubules (MTs). Cytoskeletonbinding agents, that alter the architecture and dynamics of MFs and MTs, were used to study the role of cytoskeleton on PIXV replication. The …

Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus

Physiology Faculty Publications

Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer’s disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro. Lastly, although the ABCA7 isoform with an extended …

Hepatic Changes Associated With Chronic Alcohol Exposure In An Alpha-1 Antitrypsin Piz Mouse Model, Zhuoyao Lyu, Alisha M. Gruntman, Brian O'Sullivan-Murphy, Christian Mueller, Terence R. Flotte

Christian Mueller

The PiZ mutation in the alpha-1 antitrypsin (AAT) gene causes the PiZ mutant protein to be sequestered in the endoplasmic reticulum of hepatocytes, causing significant liver pathology in ~10% of PiZZ homozygous AAT disease patients. Current transgenic mouse models of the disease include the liver-specific over-expression of mutant PiZ protein. However, these animal models do not efficiently recapitulate the liver damage found in PiZZ homozygous patients. Since only a small percentage of patients develop liver disease and it is not reproducible in animal models of AATD, it suggests that there are other factors that participate in disease pathogenesis. Here, we …

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an overall increase …

Peripheral Inflammation, Apolipoprotein E4, And Amyloid-Β Interact To Induce Cognitive And Cerebrovascular Dysfunction, Felecia M. Marottoli, Yuriko Katsumata, Kevin P. Koster, Riya Thomas, David W. Fardo, Leon M. Tai

Biostatistics Faculty Publications

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 (APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of …

Risk For Cardiovascular Disease In Blacks With Hiv/Aids In America: A Systematic Review And Meta-Analysis, Calvin Odhiambo, Jessica Davis, Bernard Omolo

Journal of Health Disparities Research and Practice

Cardiovascular disease (CVD) related to HIV infection is becoming a major public health concern in the United Stated. Epidemiologic studies show that prolonged use of Highly Active Antiretroviral Therapy, HIV/AIDS itself, and a combination of traditional vascular risk factors increase the risk for CVD among people with HIV/AIDS. However, little is known about any racial disparities in the risk for CVD in the HIV/AIDS population. We conducted a systematic review and meta-analysis of literature on HIV/AIDS and CVD (June 1, 2010-July 31, 2014) through MEDLINE to examine whether and how HIV-positive African Americans are disproportionately affected by CVD compared to …

Residential Segregation, Neighborhood Social And Physical Context In Obesity Disparities In Hispanic Preschoolers: A Conceptual Model, Catherina Chang Martinez Phd(C), Nasar U. Ahmed Phd, Ruby A. Natale Phd, Psyd

Journal of Health Disparities Research and Practice

During the last decade, there has been a significant inclusion in obesity prevention studies from individual characteristics to household factors then neighborhood factors. The study of place in the context of early childhood obesity studies has been limited to the food and physical built environment. With the persistent disparities in the prevalence of childhood obesity, and Hispanic minorities being increasingly affected, there is a need to reexamine existing models and develop new model conceptual frameworks to examine the role of place and residential segregation in the context of race, ethnicity, social position, and socioeconomic disparities. In the context of place …

Mechanical Properties Of Retrieved Highly Cross-Linked Polyethylene Acetabular Liners In Total Hip Arthroplasty, Gurpreet Singh

Electronic Thesis and Dissertation Repository

Highly cross-linked polyethylene (HXLPE) has replaced the conventional ultra-high-molecular-weight-polyethylene (UHMWPE) as the gold standard bearing surface in total hip arthroplasty (THA) due to superior wear characteristics and survivorship. However, HXLPE has demonstrated poorer mechanical properties, in vivo oxidation, and concerns of rim fractures. The purpose of this project was to study the mechanical properties at the rim of retrieved HXLPE acetabular liners.

We developed a simple technique for measurement of hardness at the rim of irradiated, remelted, HXLPE liners of a specific design. The effect of shelf time on mechanical properties of retrieved liners was determined and showed no correlation …

Superbugs Versus Outsourced Cleaners: Employment Arrangements And The Spread Of Health Care-Associated Infections, Adam Seth Litwin, Ariel C. Avgar, Edmund R. Becker

Adam Seth Litwin

On any given day, about one in 25 hospital patients in the United States has a health care–associated infection (HAI) that the patient contracts as a direct result of his or her treatment. Fortunately, the spread of most HAIs can be halted through proper disinfection of surfaces and equipment. Consequently, cleaners—“environmental services” (EVS) in hospital parlance—must take on the important task of defending hospital patients (as well as staff and the broader community) from the spread of HAIs. Despite the importance of this task, hospitals frequently outsource this function, increasing the likelihood that these workers are under-rewarded, undertrained, and detached …

Congenital Toxoplasmosis In Austria: Prenatal Screening For Prevention Is Cost-Saving, Andrea-Romana Prusa, David C. Kasper, Larry Sawers, Evelyn Walter, Michael Hayde, Eileen Stillwaggon

Economics Faculty Publications

Background:

Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario.

Methodology/Principal Findings:

We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric …

Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique drug …

Risk Factors For Bk Virus Infection After Kidney Transplantation, London, Ontario 2016, Seyed M Hosseini-Moghaddam

Electronic Thesis and Dissertation Repository

Our objective was to determine the risk factors for BK virus infection in renal allograft recipients in the first year after transplantation. In this cohort, we included all patients who received renal allograft at London Health Sciences Centre (LHSC) between 2012 and 2014. We continued post-transplantation follow-up for one year. Of 175 patients (37% female) with median age (range) of 53 (14-82) years, 40 (22.9%) developed BK viremia (median interval:100 days, range: 35-264). Recipient age, recipient gender, hemodialysis (HD) vs peritoneal dialysis (PD), Human Leukocyte Antigens A1, B35 and Cw4 increased the risk of post-transplant BKV infection. However, donor gender, …

A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner

Biomedical Engineering ETDs

Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …

Higher Mineralized Bone Volume Is Associated With A Lower Plain X-Ray Vascular Calcification Score In Hemodialysis Patients, Teresa Adragao, Anibal Ferreira, Joao M. Frazao, Ana Luisa Papoila, Iola Pinto, Marie-Claude Monier-Faugere, Hartmut H. Malluche

Internal Medicine Faculty Publications

Background and objectives

In dialysis patients, there is an increasing evidence that altered bone metabolism is associated with cardiovascular calcifications. The main objective of this study was to analyse, in hemodialysis patients, the relationships between bone turnover, mineralization and volume, evaluated in bone biopsies, with a plain X-ray vascular calcification score.

Design, setting, participants and measurements

In a cross-sectional study, bone biopsies and evaluation of vascular calcifications were performed in fifty hemodialysis patients. Cancellous bone volume, mineralized bone volume, osteoid volume, activation frequency, bone formation rate/bone surface, osteoid thickness and mineralization lag time were determined by histomorphometry. Vascular calcifications were …

Predictors Of Gestational Weight Gain Among White And Latina Women And Associations With Birth Weight, Milagros C. Rosal, Monica L. Wang, Tiffany A. Moore Simas, Jamie S. Bodenlos, Sybil L. Crawford, Katherine Leung, Heather Z. Sankey

Heather Z Sankey MD

This study examined racial/ethnic differences in gestational weight gain (GWG) predictors and association of first-trimester GWG to overall GWG among 271 White women and 300 Latina women. Rates of within-guideline GWG were higher among Latinas than among Whites (28.7% versus 24.4%, p < 0.016). Adjusted odds of above-guideline GWG were higher among prepregnancy overweight (OR = 3.4, CI = 1.8-6.5) and obese (OR = 4.5, CI = 2.3-9.0) women than among healthy weight women and among women with above-guideline first-trimester GWG than among those with within-guideline first-trimester GWG (OR = 4.9, CI = 2.8-8.8). GWG was positively associated with neonate birth …

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein …

Alternative Interventions For Children Coping With Chronic Conditions: A Critical Review Of The Literature, Nina M. Pelsi, Kim S. Amer

DePaul Discoveries

Reduction of stressors and anxiety levels in adolescents with chronic illnesses is a critical concept in pediatric health care in America today. The many stressors associated with chronic illness include displaying physical and mental differences, social stigma, financial difficulty, and family stress. These stressors may affect the adolescent’s ability to learn and cope in everyday life. The current research was a critical review of the literature examining studies done with adolescents coping with chronic diseases and illnesses. The aim was to analyze the most efficacious non-pharmacological methods for reducing stressors in adolescents with chronic illness. A critical review of the …

Is Biological Repair Of Heart On The Horizon?, H R. Ahmad, Satwat Hashmi

Department of Biological & Biomedical Sciences

The stem cells keep us young by endogenously repairing us upon need. They do so bysmartly one step forward towards differentiation while another step backward to nurturethe undifferentiated stem cells. They are building blocks for every organ witha differential rate of repair of worn out tissues. Since stem cells can be cultured with a normal karyo type, they could be the ideal source for heart repair after myocardial infarction. As opposed to lower vertebrates and neonatal mice, cardiac regeneration in adult mammalian heart seems to be difficult to assess with a solid evidence of cytokinesis. It becomes more difficult to …

Managing Renal Cell Carcinoma Associated Paraneoplastic Syndrome With Nephron-Sparing Surgery In A Patient With Von Hippel-Lindau., John M Dibianco, Julie Y An, Sally Tanakchi, Zachary Stanik, Aidan Mcgowan, Mahir Maruf, Abhinav Sidana, Amit Lodha Jain, Akhil Muthigi, Arvin K George, Christopher Bayne, W Marston Linehan, Shawna L Boyle, Adam R Metwalli

Urology Faculty Publications

A patient with germline von Hippel-Lindau (VHL) gene alteration and history of multiple tumors present with classical paraneoplastic syndrome (PNS) associated with renal cell carcinoma (RCC). She underwent open nephron sparing surgery with resolution of symptoms. She remained without recurrence of RCC for the initial 2 years of her follow-up. To the best of our knowledge, this case represents the first in which PNS was specifically resolved using a partial nephrectomy in a patient with VHL. This case report provides initial evidence for the potential role of nephron sparing surgery in the management of paraneoplastic symptoms associated with hereditary RCC.