Digital Commons Network^™

Equine Arteritis Virus Elicits A Mucosal Antibody Response In The Reproductive Tract Of Persistently Infected Stallions, Mariano Carossino, Bettina Wagner, Alan T. Loynachan, R. Frank Cook, Igor F. Canisso, Lakshman Chelvarajan, Casey L. Edwards, Bora Nam, John F. Timoney, Peter J. Timoney, Udeni B. R. Balasuriya

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine arteritis virus (EAV) has the ability to establish persistent infection in the reproductive tract of the stallion (carrier) and is continuously shed in its semen. We have recently demonstrated that EAV persists within stromal cells and a subset of lymphocytes in the stallion accessory sex glands in the presence of a significant local inflammatory response. In the present study, we demonstrated that EAV elicits a mucosal antibody response in the reproductive tract during persistent infection with homing of plasma cells into accessory sex glands. The EAV-specific immunoglobulin isotypes in seminal plasma included IgA, IgG1, IgG3/5, and IgG4/7. Interestingly, seminal …

Systems Biology Approach To Late-Onset Alzheimer's Disease Genome-Wide Association Study Identifies Novel Candidate Genes Validated Using Brain Expression Data And Caenorhabditis Elegans Experiments, Shubhabrata Mukherjee, Joshua C. Russell, Daniel T. Carr, Jeremy D. Burgess, Mariet Allen, Daniel J. Serie, Kevin L. Boehme, John S. K. Kauwe, Adam C. Naj, David W. Fardo, Dennis W. Dickson, Thomas J. Montine, Nilufer Ertekin-Taner, Matt R. Kaeberlein, Paul K. Crane

Biostatistics Faculty Publications

Introduction—We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci.

Methods—We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions.

Results—We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ …

Hmgb1-Rage Pathway Drives Peroxynitrite Signaling-Induced Ibd-Like Inflammation In Murine Nonalcoholic Fatty Liver Disease, Varun Chandrashekaran, Ratanesh K. Seth, Diptadip Dattaroy, Firas Alhasson, Jacek Ziolenka, James Carson, Franklin G. Berger, Balaraman Kalyanaraman, Anna Mae Diehl, Saurabh Chatterjee

Faculty Publications

Recent clinical studies found a strong association of colonic inflammation and Inflammatory bowel disease (IBD)-like phenotype with NonAlcoholic Fatty liver Disease (NAFLD) yet the mechanisms remain unknown. The present study identifies high mobility group box 1 (HMGB1) as a key mediator of intestinal inflammation in NAFLD and outlines a detailed redox signaling mechanism for such a pathway. NAFLD mice showed liver damage and release of elevated HMGB1 in systemic circulation and increased intestinal tyrosine nitration that was dependent on NADPH oxidase. Intestines from NAFLD mice showed higher Toll like receptor 4 (TLR4) activation and proinflammatory cytokine release, an outcome strongly …

Increased Habenular Connectivity In Opioid Users Is Associated With An Α5 Subunit Nicotinic Receptor Genetic Variant, Kaylah Curtis, Humsini Viswanath, Kenia M Velasquez, David L Molfese, Mark J Harding, Eduardo Aramayo, Philip R Baldwin, Elisa Ambrosi, Alok Madan, Michelle Patriquin, B Christopher Frueh, J Christopher Fowler, Thomas R Kosten, David A Nielsen, Ramiro Salas

Staff and Researcher Publications

Background and objectives: Opioid use disorder (OUD) is a chronic disorder with relapse based on both desire for reinforcement (craving) and avoidance of withdrawal. The aversive aspect of dependence and relapse has been associated with a small brain structure called the habenula, which expresses large numbers of both opioid and nicotinic receptors. Additionally, opioid withdrawal symptoms can be induced in opioid-treated rodents by blocking not only opioid, but also nicotinic receptors. This receptor co-localization and cross-induction of withdrawal therefore might lead to genetic variation in the nicotinic receptor influencing development of human opioid dependence through its impact on the aversive …

Effects Of Once-Weekly Exenatide On Cardiovascular Outcomes In Type 2 Diabetes, Rury R Holman, M Angelyn Bethel, Robert J Mentz, Vivian P Thompson, Yuliya Lokhnygina, John B Buse, Juliana C Chan, Jasmine Choi, Stephanie M Gustavson, Nayyar Iqbal, Aldo P Maggioni, Steven P Marso, Peter Öhman, Neha J Pagidipati, Neil Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez

Faculty, Staff and Student Publications

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.

METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.

RESULTS: …

Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka

Department of Neuroscience Faculty Papers

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the …

Insights Into Onchocerca Volvulus Population Biology Through Multilocus Immunophenotyping, Carmelle T Norice-Tra, José Ribeiro, Sasisekhar Bennuru, Michael P Fay, Rahul Tyagi, Makedonka Mitreva, Thomas B Nutman

2010-2019 OA Pubs

We have developed a serologically based immunophenotyping approach to study Onchocerca volvulus (Ov) population diversity. Using genomic sequence data and polymerase chain reaction-based genotyping, we identified nonsynonymous single-nucleotide polymorphisms (SNPs) in the genes of 16 major immunogenic Ov proteins: Ov-CHI-1/Ov-CHI-2, Ov16, Ov-FAR-1, Ov-CPI-1, Ov-B20, Ov-ASP-1, Ov-TMY-1, OvSOD1, OvGST1, Ov-CAL-1, M3/M4, Ov-RAL-1, Ov-RAL-2, Ov-ALT-1, Ov-FBA-1, and Ov-B8. We assessed the immunoreactivity of onchocerciasis patient sera (n = 152) from the Americas, West Africa, Central Africa, and East Africa against peptides derived from 10 of these proteins containing SNPs. Statistically significant variation in immunoreactivity among the regions was seen in SNP-containing peptides …

Gucy2c Signaling Opposes The Acute Radiation-Induced Gi Syndrome., Peng Li, Evan Wuthrick, Jeff A. Rappaport, Crystal Kraft, Jieru E. Lin, Glen Marszalowicz, Adam E. Snook, Tingting Zhan, Terry M. Hyslop, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

High doses of ionizing radiation induce acute damage to epithelial cells of the gastrointestinal (GI) tract, mediating toxicities restricting the therapeutic efficacy of radiation in cancer and morbidity and mortality in nuclear disasters. No approved prophylaxis or therapy exists for these toxicities, in part reflecting an incomplete understanding of mechanisms contributing to the acute radiation-induced GI syndrome (RIGS). Guanylate cyclase C (GUCY2C) and its hormones guanylin and uroguanylin have recently emerged as one paracrine axis defending intestinal mucosal integrity against mutational, chemical, and inflammatory injury. Here, we reveal a role for the GUCY2C paracrine axis in compensatory mechanisms opposing RIGS. …

Impact Of Vitamin A And Carotenoids On The Risk Of Tuberculosis Progression, Omowunmi Aibana, Molly F Franke, Chuan-Chin Huang, Jerome T Galea, Roger Calderon, Zibiao Zhang, Mercedes C Becerra, Emily R Smith, Alayne G Ronnenberg, Carmen Contreras, Rosa Yataco, Leonid Lecca, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Low and deficient levels of vitamin A are common in low- and middle-income countries where tuberculosis burden is high. We assessed the impact of baseline levels of vitamin A and carotenoids on tuberculosis disease risk.

METHODS: We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary tuberculosis case patients in Lima, Peru. We defined case patients as human immunodeficiency virus (HIV)-negative HHCs with blood samples in whom tuberculosis disease developed ≥15 days after enrollment of the index patient. For each case patient, we randomly selected 4 controls from among contacts in whom tuberculosis …

Direct Oral Anticoagulant- Vs Vitamin K Antagonist-Related Nontraumatic Intracerebral Hemorrhage, Georgios Tsivgoulis, Vasileios-Arsenios Lioutas, Panayiotis N. Varelas, Aristeidis H. Katsanos, Nitin Goyal, Robert Mikulik, Kristian Barlinn, Christos Krogias, Vijay K. Sharma, Konstantinos Vadikolias, Efthymios Dardiotis, Theodore Karapanayiotides, Alexandra Pappa, Christina Zompola, Sokratis Triantafyllou, Odysseas Kargiotis, Michael Ioakeimidis, Sotirios Giannopoulos, Ali Kerro, Argyrios Tsantes, Chandan Mehta, Mathew Jones, Christoph Schroeder, Casey Norton, Anastasios Bonakis, Jason Chang, Anne W. Alexandrov, Panayiotis Mitsias, Andrei V. Alexandrov

Neurology Articles

OBJECTIVE: To compare the neuroimaging profile and clinical outcomes among patients with intracerebral hemorrhage (ICH) related to use of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF).

METHODS: We evaluated consecutive patients with NVAF with nontraumatic, anticoagulant-related ICH admitted at 13 tertiary stroke care centers over a 12-month period. We also performed a systematic review and meta-analysis of eligible observational studies reporting baseline characteristics and outcomes among patients with VKA- or DOAC-related ICH.

RESULTS: We prospectively evaluated 161 patients with anticoagulation-related ICH (mean age 75.6 ± 9.8 years, 57.8% men, median admission NIH Stroke …

A Pilot Clinical Trial Of Recombinant Human Angiotensin-Converting Enzyme 2 In Acute Respiratory Distress Syndrome., Akram Khan, Cody Benthin, Brian Zeno, Timothy E Albertson, John Boyd, Jason D Christie, Richard Hall, Germain Poirier, Juan J Ronco, Mark Tidswell, Kelly Hardes, William M Powley, Tracey J Wright, Sarah K Siederer, David A Fairman, David A Lipson, Andrew I Bayliffe, Aili L Lazaar

Trauma and Acute Care Articles

BACKGROUND: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury.

METHODS: We conducted a two-part phase II trial comprising an open-label intrapatient dose escalation and a randomized, double-blind, placebo-controlled phase in ten intensive care units in North America. Patients were between the ages of 18 and 80 years, had an American-European Consensus Criteria consensus diagnosis of ARDS, and had been mechanically ventilated for less than 72 h. …

Serum D-Dimer Test Is Promising For The Diagnosis Of Periprosthetic Joint Infection And Timing Of Reimplantation., Alisina Shahi, Michael M. Kheir, Majd Tarabichi, Hamid R.S. Hosseinzadeh, Timothy L. Tan, Javad Parvizi

Rothman Institute Papers

BACKGROUND: Despite the availability of a battery of tests, the diagnosis of periprosthetic joint infection (PJI) continues to be challenging. Serum D-dimer assessment is a widely available test that detects fibrinolytic activities that occur during infection. We hypothesized that patients with PJI may have a high level of circulating D-dimer and that the presence of a high level of serum D-dimer may be a sign of persistent infection in patients awaiting reimplantation.

METHODS: This prospective study was initiated to enroll patients undergoing primary and revision arthroplasty. Our cohort consisted of 245 patients undergoing primary arthroplasty (n = 23), revision for …

Activating Transcription Factor 3 Promotes Loss Of The Acinar Cell Phenotype In Response To Cerulein-Induced Pancreatitis In Mice, Elena N Fazio, Claire C Young, Jelena Toma, Michael Levy, Kurt R Berger, Charis L Johnson, Rashid Mehmood, Patrick Swan, Alphonse Chu, Sean P Cregan, F Jeffrey Dilworth, Christopher J Howlett, Christopher L Pin

Paediatrics Publications

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of >30% of differentially expressed genes during the initiation of pancreatitis. …

Overdose Deaths Related To Fentanyl And Its Analogs – Ohio, January-February 2017, Raminta Daniulaityte, Matthew P. Juhascik, Kraig E. Strayer, Ioana E. Sizemore, Kent E. Harshbarger, Heather M. Antonides, Robert G. Carlson

Population and Public Health Sciences Faculty Publications

What is already known about this topic? Illicitly manufactured fentanyl has become a significant contributor to unintentional overdose deaths in the United States. What is added by this report? Approximately 90% of unintentional overdose deaths examined in 24 Ohio counties that occurred during January–February 2017 involved fentanyl, fentanyl analogs, or both, whereas heroin was identified in the minority (6%) of cases, with somewhat higher prevalence in Appalachian counties. Fentanyl is commonly appearing in combination with other analogs. What are the implications for public health practice? These findings highlight the urgent need to make illicitly manufactured fentanyl testing a part of …

Reduced Ability Of Calcitriol To Promote Augmented Dopamine Release In The Lesioned Striatum Of Aged Rats, Wayne A. Cass, Laura E. Peters

Neuroscience Faculty Publications

Parkinson’s disease (PD) is a progressive and debilitating neurodegenerative disorder that affects over one million people in the United States. Previous studies, carried out in young adult rats, have shown that calcitriol, the active metabolite of vitamin D, can be neuroprotective in 6-hydroxydopamine (6-OHDA) models of PD. However, as PD usually affects older individuals, the ability of calcitriol to promote dopaminergic recovery was examined in lesioned young adult (4 month old), middle-aged (14 month old) and aged (22 month old) rats. Animals were given a single injection of 12 μg 6-OHDA into the right striatum. Four weeks later they were …

Intracranial Eeg Fluctuates Over Months After Implanting Electrodes In Human Brain., Hoameng Ung, Steven N. Baldassano, Hank Bink, Abba M. Krieger, Shawniqua Williams, Flavia Vitale, Chengyuan Wu, Dean Freestone, Ewan Nurse, Kent Leyde, Kathryn A. Davis, Mark Cook, Brian Litt

Department of Neurosurgery Faculty Papers

OBJECTIVE: Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings.

APPROACH: Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for …

Strain Specific Effects Of Low Level Lead Exposure On Associative Learning And Memory In Rats., Megha Verma, J. S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Exposure to lead (Pb) remains a significant public health concern. Lead exposure in early life impairs the normal development of numerous cognitive and neurobehavioral processes. Previous work has shown that the effects of developmental Pb exposure on gene expression patterns in the brain are modulated by various factors including the developmental timing of the exposure, level of exposure, sex, and genetic background. Using gene microarray profiling, we previously reported a significant strain-specific effect of Pb exposure on the hippocampal transcriptome, with the greatest number of differentially expressed transcripts in Long Evans (LE) rats and the fewest in Sprague Dawley (SD) …

Amlexanox Enhances Premature Termination Codon Read-Through In Col7a1 And Expression Of Full Length Type Vii Collagen: Potential Therapy For Recessive Dystrophic Epidermolysis Bullosa., Velina S. Atanasova, Qiujie Jiang, Marco Prisco, Christina Gruber, Josefina Piñón Hofbauer, Mei Chen, Cristina Has, Leena Bruckner-Tuderman, John A. Mcgrath, Jouni Uitto, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder caused by the lack of functional type VII collagen, leading to skin fragility and subsequent trauma-induced separation of the epidermis from the underlying dermis. A total of 46% of patients with RDEB harbor at least one premature termination codon (PTC) mutation in COL7A1, and previous studies have shown that aminoglycosides are able to overcome RDEB PTC mutations by inducing "read-through" and incorporation of an amino acid at the PTC site. However, aminoglycoside toxicity will likely prevent widespread clinical application. Here the FDA-approved drug amlexanox was tested for its ability …

Targeting Hepatic Heparin-Binding Egf-Like Growth Factor (Hb-Egf) Induces Anti-Hyperlipidemia Leading To Reduction Of Angiotensin Ii-Induced Aneurysm Development, Seonwook Kim, Lihua Yang, Seongu Kim, Richard G. Lee, Mark J. Graham, Judith A. Berliner, Aldons J. Lusis, Lei Cai, Ryan E. Temel, Debra L. Rateri, Sangderk Lee

Saha Cardiovascular Research Center Faculty Publications

Objective

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model.

Approach and results

Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin …

Idarucizumab For Dabigatran Reversal - Full Cohort Analysis., Charles V. Pollack, Paul A. Reilly, Joanne Van Ryn, John W. Eikelboom, Stephan Glund, Richard A. Bernstein, Robert Dubiel, Menno V. Huisman, Elaine M. Hylek, Chak-Wah Kam, Pieter W. Kamphuisen, Jörg Kreuzer, Jerrold H. Levy, Gordon Royle, Frank W. Sellke, Joachim Stangier, Thorsten Steiner, Peter Verhamme, Bushi Wang, Laura Young, Jeffrey I. Weitz

Department of Emergency Medicine Faculty Papers

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran.

METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration …

(Re)Grounding Grounded Theory: A Close Reading Of Theory In Four Schools, Tavis Apramian, Sayra Cristancho, Chris Watling, Lorelei Lingard

Health and Rehabilitation Sciences Publications

The debate over what counts as theory has dominated methodological conversations in grounded theory research for decades. Four of the schools of thought in that debate – Glaserian, Straussian, Charmazian, and Clarkeian – hold different assumptions about what theory is and how it is made. The first two schools understand theory as an abstraction that exactingly accounts for exceptions. The second two schools understand theory as a process of describing voices hidden from public view. While Glaserian and Straussian coding processes focus on coding exceptions, Charmazian and Clarkeian coding processes focus on building a story of the participants or social …

A Naturally Generated Decoy Of The Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance In Tumors, Nikhil Hebbar, Ravshan Burikhanov, Nidhi Shukla, Shirley Qiu, Yanming Zhao, Kojo S. J. Elenitoba-Johnson, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth. A VASA segment of Par-4 mediated its binding and degradation by the ubiquitin ligase Fbxo45, resulting in loss of Par-4 proapoptotic function. Conversely, PAF, which contains this VASA …

Increased Expression Of M1 And M2 Phenotypic Markers In Isolated Microglia After Four-Day Binge Alcohol Exposure In Male Rats, Hui Peng, Chelsea Rhea Geil Nickell, Kevin Y. Chen, Justin A. Mcclain, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Microglia activation and neuroinflammation are common features of neurodegenerative conditions, including alcohol use disorders (AUDs). When activated, microglia span a continuum of diverse phenotypes ranging from classically activated, pro-inflammatory (M1) microglia/macrophages to alternatively activated, growth-promoting (M2) microglia/macrophages. Identifying microglia phenotypes is critical for understanding the role of microglia in the pathogenesis of AUDs. Therefore, male rats were gavaged with 25% (w/v) ethanol or isocaloric control diet every 8 h for 4 days and sacrificed at 0, 2, 4, and 7 days after alcohol exposure (e.g., T0, T2, etc.). Microglia were isolated from hippocampus and entorhinal cortices by Percoll density gradient …

The Impact Of Smoking On Sentinel Node Metastasis Of Primary Cutaneous Melanoma., Maris S Jones, Peter C Jones, Stacey L Stern, David Elashoff, Dave S B Hoon, John Thompson, Nicola Mozzillo, Omgo E Nieweg, Dirk Noyes, Harald J Hoekstra, Jonathan S Zager, Daniel F Roses, Alessandro Testori, Brendon J Coventry, Mark B Smithers, Robert Andtbacka, Doreen Agnese, Erwin Schultz, Eddy C Hsueh, Mark Kelley, Schlomo Schneebaum, Lisa Jacobs, Tawnya Bowles, Mohammed Kashani-Sabet, Douglas Johnson, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy.

METHODS: Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis.

RESULTS: Current smoking was strongly associated with SLN metastasis (p = 0.004), even after adjusting for other predictors of metastasis. Among …

A Randomized Placebo-Controlled Trial Of N-Acetylcysteine For Cannabis Use Disorder In Adults, Kevin M. Gray, Susan C. Sonne, Erin A. Mcclure, Udi E. Ghitza, Abigail G. Matthews, Aimee L. Mcrae-Clark, Kathleen M. Carroll, Jennifer S. Potter, Katharina Wiest, Larissa J. Mooney, Albert Hasson, Sharon L. Walsh, Michelle R. Lofwall, Shanna Babalonis, Robert W. Lindblad, Steven Sparenborg, Aimee Wahle, Jacqueline S. King, Nathaniel L. Baker, Rachel L. Tomko, Louise F. Haynes, Ryan G. Vandrey, Frances R. Levin

Behavioral Science Faculty Publications

Background—Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults.

Methods—In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All …

Using Neonatal Skin To Study The Developmental Programming Of Aging, Leryn J. Reynolds, Brett J. Dickens, Benjamin B. Green, Carmen J. Marsit, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Numerous studies have examined how both negative and positive maternal exposures (environmental contaminants, nutrition, exercise, etc.) impact offspring risk for age-associated diseases such as obesity, type 2 diabetes, hypertension, and others. The purpose of this study was to introduce the foreskin as a novel model to examine developmental programming in human neonates, particularly in regard to adipogenesis and insulin receptor signaling, major contributors to age-associated diseases such as obesity and diabetes. Neonatal foreskin was collected following circumcision and primary dermal fibroblasts were isolated to perform adipocyte differentiation and insulin stimulation experiments. Human neonatal foreskin primary fibroblasts take up lipid when …

In Vivo Evaluation Of Stem Cell Aggregates On Osteochondral Regeneration., Banupriya Sridharan, Amy D. Laflin, Michael A. Holtz, Donna M. Pacicca, Nicholas K. Wischmeier, Michael S. Detamore

Manuscripts, Articles, Book Chapters and Other Papers

To date, many osteochondral regenerative approaches have utilized varied combinations of biocompatible materials and cells to engineer cartilage. Even in cell-based approaches, to date, no study has utilized stem cell aggregates alone for regenerating articular cartilage. Thus, the purpose of this study was to evaluate the performance of a novel stem cell-based aggregate approach in a fibrin carrier to regenerate osteochondral defects in the Sprague-Dawley rat trochlear groove model. Two different densities of rat bone marrow mesenchymal stem cell (rBMSC) aggregates were fabricated by the hanging drop technique. At 8 weeks, the cell aggregates supported the defects and served as …

Seroepidemiology Of Sarcocystis Neurona And Neospora Hughesi Infections In Domestic Donkeys (Equus Asinus) In Durango, Mexico, Cosme Alvarado-Esquivel, Daniel K. Howe, Michelle R. Yeargan, Domingo Alvarado-Esquivel, José Alfredo Zamarripa-Barboza, Jitender P. Dubey

Maxwell H. Gluck Equine Research Center Faculty Publications

There is currently no information regarding Sarcocystis neurona and Neospora hughesi infections in donkeys in Mexico. Here, we determined the presence of antibodies against S. neurona and N. hughesi in donkeys in the northern Mexican state of Durango. Serum samples of 239 domestic donkeys (Equus asinus) were assayed for S. neurona and N. hughesi antibodies using home-made enzyme-linked immunoassays; six (2.5%) of the 239 donkeys tested seropositive for S. neurona. The seroprevalence of S. neurona infection was comparable among donkeys regardless of their origin, health status, or sex. Multivariate analysis showed that seropositivity to S. neurona was …

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 …

Tumor-Treating Fields Plus Chemotherapy Versus Chemotherapy Alone For Glioblastoma At First Recurrence: A Post Hoc Analysis Of The Ef-14 Trial., Santosh Kesari, Zvi Ram

Articles, Abstracts, and Reports

BACKGROUND: This post hoc analysis of the EF-14 trial (NCT00916409) of tumor-treating fields (TTFields) plus temozolomide versus temozolomide alone in newly diagnosed glioblastoma compared the efficacy of TTFields plus chemotherapy (physician's choice) versus chemotherapy alone after first recurrence.

METHODS: Patients on TTFields plus temozolomide continued TTFields plus second-line chemotherapy after first recurrence. Some patients on temozolomide alone crossed over after approval of TTFields for recurrent GBM. The primary efficacy outcome was overall survival (OS).

RESULTS: After disease progression, 131 patients received TTFields plus chemotherapy and 73 chemotherapy alone. Thirteen patients in the original temozolomide-alone group crossed over to receive TTFields …