Digital Commons Network^™

Clinical Characteristics And Treatment Patterns Of Children And Adults With Iga Nephropathy Or Iga Vasculitis: Findings From The Curegn Study., David T. Selewski, Josephine M. Ambruzs, Gerald B. Appel, Andrew S. Bomback, Raed Bou Matar, Yi Cai, Daniel C. Cattran, Aftab S. Chishti, Vivette D. D'Agati, Cynthia J. D'Alessandri-Silva, Rasheed A. Gbadegesin, Jonathan J. Hogan, Sandra Iragorri, J Charles Jennette, Bruce A. Julian, Myda Khalid, Richard A. Lafayette, Helen Liapis, Francesca Lugani, Sarah A. Mansfield, Sherene Mason, Patrick H. Nachman, Cynthia C. Nast, Carla M. Nester, Damien G. Noone, Jan Novak, Michelle M. O'Shaughnessy, Heather N. Reich, Michelle N. Rheault, Dana V. Rizk, Manish K. Saha, Neil S. Sanghani, C John Sperati, Rajasree Sreedharan, Tarak Srivastava, Agnieszka Swiatecka-Urban, Katherine Twombley, Tetyana L. Vasylyeva, Donald J. Weaver, Hong Yin, Jarcy Zee, Ronald J. Falk, Ali G. Gharavi, Brenda W. Gillespie, Debbie S. Gipson, Larry A. Greenbaum, Lawrence B. Holzman, Matthias Kretzler, Bruce M. Robinson, William E. Smoyer, Michael Flessner, Lisa M. Guay-Woodford, Krzysztof Kiryluk, Curegn Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients.

Methods: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment.

Results: A total of 667 patients (506 IgAN, 161 IgAV) constitute …

Proteomics Of Human Liver Membrane Transporters: A Focus On Fetuses And Newborn Infants., Bianca D. Van Groen, Evita Van De Steeg, Miriam G. Mooij, Marola M H Van Lipzig, Barbara A E De Koning, Robert M. Verdijk, Heleen M. Wortelboer, R Gaedigk, Chengpeng Bi, J Steven Leeder, Ron H N Van Schaik, Joost Van Rosmalen, Dick Tibboel, Wouter H. Vaes, Saskia N. De Wildt

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples.

METHODS: Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3, NTCP, OCT1, OATP1B1, OATP1B3, OATP2B1 and ATP1A1 were quantified with LC-MS/MS in isolated crude membrane fractions of snap-frozen post-mortem fetal and pediatric, and surgical adult liver samples. mRNA expression was quantified using RNA sequencing, and genetic variants with TaqMan assays. We explored relationships between protein expression and age …

Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. Curtis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Current laboratory testing of cerebrospinal fluid (CSF) does not consistently discriminate between different central nervous system (CNS) disease states. Rapidly distinguishing CNS infections from other brain and spinal cord disorders that share a similar clinical presentation is critical. New approaches focusing on aspects of disease biology, such as immune response profiles that can have stimulus-specific attributes, may be helpful. We undertook this preliminary proof-of-concept study using multiplex ELISA to measure CSF cytokine levels in various CNS disorders (infections, autoimmune/demyelinating diseases, lymphomas, and gliomas) to determine the potential utility of cytokine patterns in differentiating CNS infections from other CNS diseases. Both …

Neutrophil To Lymphocyte Ratio: A Prognostic Indicator For Astronaut Health, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Brian Crucian, Sharmila Bhattacharya

Publications

Short-term and long-term spaceflight missions can cause immune system dysfunction in astronauts. Recent studies indicate elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in astronaut blood, along with unchanged or reduced lymphocyte counts, and reduced T cell function, during short-(days) and long-(months) term spaceflight. A high PMN to lymphocyte ratio (NLR) can acts as a strong predictor of poor prognosis in cancer, and as a biomarker for subclinical inflammation in humans and chronic stress in mouse models, however, the NLR has not yet been identified as a predictor of astronaut health during spaceflight. For this, complete blood cell count …

The Influence Of Body Mass Index On Survival And Length Of Stay In Patients With Septic Shock, Yasir Jawaid, Waseem Ahmed, Damir Kusmic, Aman Ajmeri, Kanaan Mansoor, Cristie Mannino, Thomas Judge, Larry E. Carter, Akash V. Ajmera

Marshall Journal of Medicine

Background: Obesity is one of the most widespread epidemics of our time. In fact, currently 65.7% of US adults age 20 and older are overweight, while 30.6% are obese. It has been well-established that obesity has numerous adverse effects on long-term health, however the specific effect on patients treated for sepsis and septic shock is unclear. Body Mass Index (BMI) is a measure of total body fat content and surrogate marker for obesity. In our study, we aimed to identify if BMI was an independent risk factor for poor survival or increased length of stay (LOS) in patients with sepsis. …

Predominance Of Triple Wild-Type And Igf2r Mutations In Mucosal Melanomas., Yuuki Iida, Matthew P Salomon, Keisuke Hata, Kevin Tran, Shuichi Ohe, Chester Griffiths, Sandy C Hsu, Nellie Nelson, Dave S B Hoon

Articles, Abstracts, and Reports

BACKGROUND: Primary mucosal melanoma (MM) is a rare subtype of melanoma that arises from melanocytes in the mucosa. MM has not been well profiled for mutations and its etiology is not well understood, rendering current treatment strategies unsuccessful. Hence, we investigated mutational landscape for MM to understand its etiology and to clarify mutations that are potentially relevant for MM treatment.

METHODS: Forty one MM and 48 cutaneous melanoma (CM) tissues were profiled for mutations using targeted deep next-generation sequencing (NGS) for 89 cancer-related genes. A total of 997 mutations within exons were analyzed for their mutational spectrum and prevalence of …

Forecast Or Fall: Prediction's Importance To Postural Control, Chris J. Dakin, David A.E. Bolton

Kinesiology and Health Science Faculty Publications

To interact successfully with an uncertain environment, organisms must be able to respond to both unanticipated and anticipated events. For unanticipated events, organisms have evolved stereotyped motor behaviors mapped to the statistical regularities of the environment, which can be trigged by specific sensory stimuli. These 'reflexive' responses are more or less hardwired to prevent falls and represent, maybe, the best available solution to maintaining posture given limited available time and information. With the gift of foresight, however, motor behaviors can be tuned or prepared in advance, improving the ability of the organism to compensate for, and interact with, the changing …

Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Objective: To assess the potential relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China.

Methods: A case–control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures.

Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% …

Glimepiride Administered In Chow Reversibly Impairs Glucose Tolerance In Mice, Dana M. Niedowicz, Sabire Özcan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Sulfonylureas are a class of antidiabetes medications prescribed to millions of individuals worldwide. Rodents have been used extensively to study sulfonylureas in the laboratory. Here, we report the results of studies treating mice with a sulfonylurea (glimepiride) in order to understand how the drug affects glucose homeostasis and tolerance. We tested the effect of glimepiride on fasting blood glucose, glucose tolerance, and insulin secretion, using glimepiride sourced from a local pharmacy. We also examined the effect on glucagon, gluconeogenesis, and insulin sensitivity. Unexpectedly, glimepiride exposure in mice was associated with fasting hyperglycemia, glucose intolerance, and decreased insulin. There was no …

Patient Barriers For Weight Management Among African American Women, Owen Bowie, Jennifer Kusch, George L. Morris Iii, Tracy Flood, Jessica Gill, Renee E. Walker, Ron A. Cisler, Jennifer T. Fink

Journal of Patient-Centered Research and Reviews

Purpose: The primary aim of this study was to assess the perceptions of local African American women who are overweight or obese using semi-structured focus groups to identify barriers to weight management and factors that support strategy success. The secondary aim of this study was to determine recommendations for patient-centered weight management interventions established specifically for African American women in the Milwaukee-area community.

Methods: Three semi-structured focus groups to explore barriers to weight management were performed among women patients. Participants (N = 41) were recruited via email, postal mail, and phone as available from an academic medical center in Milwaukee, …

Conference Proceedings: Aurora Scientific Day 2018

Journal of Patient-Centered Research and Reviews

This journal supplement includes selected abstracts from among the more than 50 presented at the 44th annual Aurora Scientific Day research symposium. Held May 25, 2018, in Milwaukee, Wisconsin, Aurora Scientific Day provides a forum for original research conducted by faculty, fellows, residents, and other allied health professionals affiliated with Aurora Health Care, an integrated health system with hospitals and clinics in Wisconsin and Illinois.

Stress-Induced Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya

Publications

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role …

Bacterial Contamination Of Platelets For Transfusion: Strategies For Prevention., Jerrold H. Levy, Matthew D. Neal, Jay H. Herman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Platelet transfusions carry greater risks of infection, sepsis, and death than any other blood product, owing primarily to bacterial contamination. Many patients may be at particular risk, including critically ill patients in the intensive care unit. This narrative review provides an overview of the problem and an update on strategies for the prevention, detection, and reduction/inactivation of bacterial contaminants in platelets. Bacterial contamination and septic transfusion reactions are major sources of morbidity and mortality. Between 1:1000 and 1:2500 platelet units are bacterially contaminated. The skin bacterial microflora is a primary source of contamination, and enteric contaminants are rare but may …

Collagen Prolyl 4-Hydroxylase 1 Is Essential For Hif-1Α Stabilization And Tnbc Chemoresistance, Gaofeng Xiong, Rachel L. Stewart, Jie Chen, Tianyan Gao, Timothy L. Scott, Luis M. Samayoa, Kathleen L. O'Connor, Andrew N. Lane, Ren Xu

Markey Cancer Center Faculty Publications

Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived …

Metabolic Reprogramming Of Murine Cardiomyocytes During Autophagy Requires The Extracellular Nutrient Sensor Decorin., Maria A. Gubbiotti, Erin L. Seifert, Ulrich Rodeck, Jan B. Hoek, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The extracellular matrix is a master regulator of tissue homeostasis in health and disease. Here we examined how the small, leucine-rich, extracellular matrix proteoglycan decorin regulates cardiomyocyte metabolism during fasting in vivo. First, we validated in Dcn^-/- mice that decorin plays an essential role in autophagy induced by fasting. High-Throughput metabolomics analyses of cardiac tissue in Dcn^-/- mice subjected to fasting revealed striking differences in the hexosamine biosynthetic pathway resulting in aberrant cardiac O-β-N-Acetylglycosylation as compared with WT mice. Functionally, Dcn^-/- mice maintained cardiac function at a level comparable with nonfasted animals whereas fasted WT mice showed …

Multiple Tumor Suppressors Regulate A Hif-Dependent Negative Feedback Loop Via Isgf3 In Human Clear Cell Renal Cancer., Lili Liao, Zongzhi Z. Liu, Lauren Langbein, Weijia Cai, Eun-Ah Cho, Jie Na, Xiaohua Niu, Wei Jiang, Zhijiu Zhong, Wesley L. Cai, Geetha Jagannathan, Essel Dulaimi, Joseph R. Testa, Robert G. Uzzo, Yuxin Wang, George R. Stark, Jianxin Sun, Stephen C. Peiper, Yaomin Xu, Qin Yan, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft …

Myocardial Ischemia Reperfusion Injury: Apoptotic, Inflammatory And Oxidative Stress Role Of Galectin-3, Suhail Al-Salam, Satwat Hashmi

Department of Biological & Biomedical Sciences

Background/aims: Myocardial reperfusion has the potential to salvage the ischemic myocardium after a period of coronary occlusion. Reperfusion, however, can cause a wide spectrum of deleterious effects. Galectin-3 (GAL-3), a beta galactoside binding lectin, is closely associated with myocardial infarction (MI), myocardial fibrosis and heart failure. In our study, we investigated its role in ischemia-reperfusion injuries (IR) as this phenomenon is extremely relevant to the early intervention after acute MI.
Methods: C57B6/J wild type (WT) mice and GAL-3 knockout (KO) mice were used for murine model of IR injury in the heart where a period of 30 minutes ischemia was …

Synthesis And Antiproliferative Activities Of Doxorubicin Thiol Conjugates And Doxorubicin-Ss-Cyclic Peptide, Shaban Darwish, Neda Sadeghiani, Shirley Fong, Saghar Mozaffari, Parinaz Hamidi, Thimanthi Withana, Sun Yang, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Myocardial toxicity and drug resistance caused by drug efflux are major limitations of doxorubicin (Dox)-based chemotherapy. Dox structure modification could be used to develop conjugates with an improved biological profile, such as antiproliferative activity and higher cellular retention. Thus, Dox thiol conjugates, Dox thiol (Dox-SH), thiol-reactive Dox-SS-pyridine (SS = disulfide), and a Dox-SS-cell-penetrating cyclic peptide, Dox-SS-[C(WR)4K], were synthesized. Dox was reacted with Traut's reagent to generate Dox-SH. The thiol group was activated by the reaction with dithiodipyridine to afford the corresponding Dox-SS-Pyridine (Dox-SS-Pyr). A cyclic cell-penetrating peptide containing a cysteine residue [C(WR)4K] was prepared using Fmoc solid-phase strategy. Dox-SS-Py was …

Modulation Of Hypoxia-Induced Chemoresistance To Polymeric Micellar Cisplatin: The Effect Of Ligand Modification Of Micellar Carrier Versus Inhibition Of The Mediators Of Drug Resistance, Hoda Soleymani Abyaneh, Amir Hassan Soleimani, Mohammad Reza Vakili, Rania Soudy, Kamaljit Kaur, Francesco Cuda, Ali Tavassoli, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the modulation of HICR against cisplatin micelles: a) the development of actively targeted micelles; and b) combination therapy with modulators of HICR in MDA-MB-231 cells. Actively targeted cisplatin micelles were prepared through surface modification of acetal-poly(ethylene oxide)-poly(-carboxyl-"-caprolactone) (acetal-PEO-PCCL) micelles with epidermal growth factor receptor (EGFR)-targeting peptide, GE11 (YHWYGYTPQNVI). Our results showed that hypoxia induced resistance against free and …

Gene Gangs Of The Chloroviruses: Conserved Clusters Of Collinear Monocistronic Genes, Phillip Seitzer, Adrien Jeanniard, Fangrui Ma, James L. Van Etten, Marc T. Facciotti, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses (family Phycodnaviridae) are dsDNA viruses found throughout the world’s inland waters. The open reading frames in the genomes of 41 sequenced chloroviruses (330 + 40 kbp each) representing three virus types were analyzed for evidence of evolutionarily conserved local genomic “contexts”, the organization of biological information into units of a scale larger than a gene. Despite a general loss of synteny between virus types, we informatically detected a highly conserved genomic context defined by groups of three or more genes that we have termed “gene gangs”. Unlike previously described local genomic contexts, the definition of gene gangs requires only …

Exome Sequencing Identifies Gene Variants And Networks Associated With Extreme Respiratory Outcomes Following Preterm Birth, Aaron Hamvas, Rui Feng, Yingtao Bi, Fan Wang, Soumyaroop Bhattacharya, Jared Mereness, Madhurima Kaushal, C Michael Cotten, Philip L Ballard, Thomas J Mariani

Faculty, Staff and Student Publications

BACKGROUND: Previous studies have identified genetic variants associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants. However, findings with genome-wide significance have been rare, and not replicated. We hypothesized that whole exome sequencing (WES) of premature subjects with extremely divergent phenotypic outcomes could facilitate the identification of genetic variants or gene networks contributing disease risk.

RESULTS: The Prematurity and Respiratory Outcomes Program (PROP) recruited a cohort of > 765 extremely preterm infants for the identification of markers of respiratory morbidity. We completed WES on 146 PROP subjects (85 affected, 61 unaffected) representing extreme phenotypes of early respiratory morbidity. We tested for …

Expression Analysis Of Cyclooxygenase-2 In Patients Suffering From Esophageal Squamous Cell Carcinoma, Shahida Tasneem, Muhammad Tahir Sarwa, Muhammad Rizwan Bashi, Hamid Hussain, Jawad Ahmed, Shahid Pervez

Department of Pathology and Laboratory Medicine

Esophageal squamous cell carcinoma (ESCC) is one of the aggressive malignancies and mechanisms underlying its pathogenesis remain unclear. Cyclooxygenase-2 (COX-2) enzyme system plays a crucial role in many gastrointestinal malignancies and is an important regulator of cell growth, proliferation, apoptosis, differentiation and transformation. More precise outcome of COX-2 in ESCC is less investigated. In this study we investigated the risk factors of ESCC and expression of COX-2 in Carcinoma in situ (CIS) and ESCC compared to normal esophageal mucosa. ESCC relationship to clinico-pathological parameters using immunohistochemistry was also part of this investigation. Current study was conducted in the Institute of …

The Impact Of Stuttering On Development Of Self-Identity, Relationships, And Quality Of Life In Women Who Stutter, Charn Nang, Deborah J. Hersh, Katie Milton, Su Re Lau

Research outputs 2014 to 2021

Purpose: The experiences of women who stutter have been underresearched. Clinicians have little guidance from the research literature on issues specific to women who stutter and are likely to have less clinical contact with this group than with men who stutter because of the higher prevalence of stuttering in men. This study explored the experiences of a small group of women who stutter with a particular focus on what the main current issues are and how gender may have influenced experiences with stuttering.

Method: This qualitative study involved recruitment of 9 women who stutter (aged 35-80 years) through a support …

Dual Inhibition Of Bcl-2/Bcl-Xl And Xpo1 Is Synthetically Lethal In Glioblastoma Model Systems, Enyuan Shang, Yiru Zhang, Chang Shu, Chiaki Tsuge Ishida, Elena Bianchetti, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

XPO1 has recently emerged as a viable treatment target for solid malignancies, including glioblastoma (GBM), the most common primary malignant brain tumor in adults. However, given that tumors become commonly resistant to single treatments, the identification of combination therapies is critical. Therefore, we tested the hypothesis that inhibition of anti-apoptotic Bcl-2 family members and XPO1 are synthetically lethal. To this purpose, two clinically validated drug compounds, the BH3-mimetic, ABT263, and the XPO1 inhibitor, Selinexor, were used in preclinical GBM model systems. Our results show that inhibition of XPO1 reduces cellular viability in glioblastoma cell cultures. Moreover, addition of ABT263 significantly …

Effect Of Aspirin On Cardiovascular Events And Bleeding In The Healthy Elderly, John J Mcneil, Rory Wolfe, Robyn L Woods, Andrew M Tonkin, Geoffrey A Donnan, Mark R Nelson, Christopher M Reid, Jessica E Lockery, Brenda Kirpach, Elsdon Storey, Raj C Shah, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Colin I Johnston, Joanne Ryan, Barbara Radziszewska, Michael Jelinek, Mobin Malik, Charles B Eaton, Donna Brauer, Geoff Cloud, Erica M Wood, Suzanne E Mahady, Suzanne Satterfield, Richard Grimm, Anne M Murray

Faculty, Staff and Student Publications

BACKGROUND: Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk.

METHODS: From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a …

Effect Of Aspirin On All-Cause Mortality In The Healthy Elderly, John J Mcneil, Mark R Nelson, Robyn L Woods, Jessica E Lockery, Rory Wolfe, Christopher M Reid, Brenda Kirpach, Raj C Shah, Diane G Ives, Elsdon Storey, Joanne Ryan, Andrew M Tonkin, Anne B Newman, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Geoffrey A Donnan, Peter Gibbs, Colin I Johnston, Barbara Radziszewska, Richard Grimm, Anne M Murray

Faculty, Staff and Student Publications

BACKGROUND: In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo.

METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics …

Effect Of Aspirin On Disability-Free Survival In The Healthy Elderly, John J Mcneil, Robyn L Woods, Mark R Nelson, Christopher M Reid, Brenda Kirpach, Rory Wolfe, Elsdon Storey, Raj C Shah, Jessica E Lockery, Andrew M Tonkin, Anne B Newman, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Geoffrey A Donnan, Peter Gibbs, Colin I Johnston, Joanne Ryan, Barbara Radziszewska, Richard Grimm, Anne M Murray

Faculty, Staff and Student Publications

BACKGROUND: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.

METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end …

Leukemia Inhibitory Factor Modulates The Peripheral Immune Response In A Rat Model Of Emergent Large Vessel Occlusion, Stephanie M. Davis, Lisa A. Collier, Edric D. Winford, Christopher C. Leonardo, Craig T. Ajmo Jr., Elspeth A. Foran, Timothy J. Kopper, John C. Gensel, Keith R. Pennypacker

Neurology Faculty Publications

Background: The migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation of antioxidant enzymes, promotes an anti-inflammatory phenotype in several types of immune cells. The goal of this study was to determine whether LIF treatment modulates the peripheral immune response after stroke.

Methods: Young male (3 month) Sprague-Dawley rats underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals were administered LIF (125 μg/kg) or …

Cd133 Expression In Glioblastoma Multiforme: A Literature Review, Syed Ijlal Ahmed, Gohar Javed, Altaf Ali Laghari, Syeda Beenish Bareeqa, Saba Farrukh, Shajeeah Zahid, Syeda Sana Samar, Kashif Aziz

Section of Neurosurgery

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most common primary brain tumor. Extensive research has been carried out to discover the factors associated with the course and progression of GBM. CD133 is a glycoprotein antigen found in normal and malignant tissues. CD133 has been recognized as a marker for the growth of cancer cells. The association between this tissue marker and GBM is being investigated. The aim of this review was to evaluate the role of CD133 as a tumor marker for the prognosis of GBM.

Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Metformin, an oral anti-hyperglycemic drug which inhibits mitochondrial complex I and oxidative phosphorylation has been reported to correlate with improved outcomes in head and neck squamous cell carcinoma (HNSCC) and other cancers. This effect is postulated to occur through disruption of tumor-driven metabolic and immune dysregulation in the tumor microenvironment (TME). We report new findings on the impact of metformin on the tumor and immune elements of the TME from a clinical trial of metformin in HNSCC. Methods: Human papilloma virus-(HPV-) tobacco+ mucosal HNSCC samples (n = 12) were compared to HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples (n …