Digital Commons Network^™

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 …

Sustained Efficacy, Safety And Patient-Reported Outcomes Of Certolizumab Pegol In Axial Spondyloarthritis: 4-Year Outcomes From Rapid-Axspa., Désirée Van Der Heijde, Maxime Dougados, Robert Landewé, Joachim Sieper, Walter P Maksymowych, Martin Rudwaleit, Filip Van Den Bosch, Jürgen Braun, Philip Mease, Alan J Kivitz, Jessica Walsh, Owen Davies, Lars Bauer, Bengt Hoepken, Luke Peterson, Atul Deodhar

Articles, Abstracts, and Reports

Objective: The aim was to assess the long-term safety and efficacy of certolizumab pegol over 4 years of continuous treatment in patients with axial spondyloarthritis (axSpA), including both AS and non-radiographic (nr-) axSpA.

Methods: RAPID-axSpA was a phase 3 randomized trial, double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Patients had a clinical diagnosis of axSpA, meeting Assessment of SpondyloArthritis international Society (ASAS) criteria, and had active disease. The assessed outcomes included ASAS20, ASAS40, AS DAS (ASDAS), BASDAI, BASFI and BASMI scores, along with selected measures of remission. Further …

Probing The Metabolic Phenotype Of Breast Cancer Cells By Multiple Tracer Stable Isotope Resolved Metabolomics, Andrew N. Lane, Julie Tan, Yali Wang, Jun Yan, Richard M. Higashi, Teresa W. -M. Fan

Center for Environmental and Systems Biochemistry Faculty Publications

Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using ¹³C₆-glucose, ¹³C-1+2-glucose, ¹³C₅,¹⁵N₂-Gln, ¹³C₃-glycerol, and ¹³C₈-octanoate as tracers. These tracers were designed to probe the central energy producing …

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 …

Healthcare Contact And Treatment Uptake Following Hepatitis C Virus Screening And Counseling Among Rural Appalachian People Who Use Drugs, Dustin B. Stephens, April M. Young, Jennifer R. Havens

Behavioral Science Faculty Publications

Background—Hepatitis C virus (HCV) remains a major contributor to morbidity and mortality worldwide. Since 2009, Kentucky has led the United States in cases of acute HCV, driven largely by injection drug use in rural areas. Improved treatment regimens hold promise of mitigating the impact and transmission of HCV, but numerous barriers obstruct people who inject drugs (PWID) from receiving care, particularly in medically underserved settings.

Methods—503 rural people who use drugs were recruited using respondent-driven sampling and received HCV screening and post-test counseling. Presence of HCV antibodies was assessed using enzyme immunoassay of dried blood samples. Sociodemographic and …

Multimodality Therapy Improves Survival In Intramedullary Spinal Cord Metastasis Of Lung Primary, Hayder Saeed, Reema Patel, Jigisha Thakkar, Lames Hamoodi, Li Chen, John L. Villano

Internal Medicine Faculty Publications

Background: Most metastatic spinal cord lesions are located either in the intradural, extramedullary, or in the epidural compartments. Intramedullary spinal cord metastasis (ISCM) is a rare central nervous system spread of cancer. The aim of this report was to evaluate ISCM in the published literature.

Methods: A literature review of PubMed from 1960 to 2016 was undertaken for the publications having demographic, clinical, histological, and outcome data.

Results: A total of 59 relevant papers were identified, showing 128 cases of intramedullary metastasis from lung cancer. The incidence of lung cancer as the primary malignancy with intramedullary metastasis was 56%. The …

A Longitudinal Study Of The Reciprocal Relationship Between Ever Smoking And Urgency In Early Adolescence, Jessica L. Burris, Elizabeth N. Riley, Gabriella E. Puleo, Gregory T. Smith

Psychology Faculty Publications

Background—Among early adolescents in the United States (U.S.), the prevalence of cigarette smoking is at its lowest level in recent decades. Nonetheless, given the risks of smoking in early development, it remains critically important to study both risk factors for smoking and risks from smoking. This longitudinal study with U.S. early adolescents examines smoking initiation and tests a model of reciprocal prediction between ever smoking and the personality trait of urgency (i.e., mood-based impulsivity), a trait that increases risk for multiple forms of dysfunction.

Methods—Participants (n=1906; 90% 10–11 years old, 50% female, 39% racial minorities at …

Tailoring A Nicu-Based Tobacco Treatment Program For Mothers Who Are Dependent On Opioids, Amanda Fallin-Bennett, Kristin Ashford

Nursing Faculty Publications

Objective—To collect formative information to design a tailored tobacco treatment intervention for women with newborns treated or evaluated for neonatal abstinence syndrome and to explore current tobacco use behaviors and facilitators and barriers to smoking cessation.

Design—Qualitative descriptive study.

Setting—An academic medical center in the southern United States.

Participants—Mothers of newborns who were treated or evaluated for neonatal abstinence syndrome at birth within the preceding three months. Women were recruited who were older than 18 and reported opioid dependence and smoking during pregnancy.

Methods—Participants took part in semi-structured individual interviews that lasted approximately one hour. …

Effects Of Intensive Bp Control In Ckd, Alfred K. Cheung, Mahboob Rahman, David M. Reboussin, Timothy E. Craven, Tom Greene, Paul L. Kimmel, William C. Cushman, Amret T. Hawfield, Karen C. Johnson, Cora E. Lewis, Suzanne Oparil, Michael V. Rocco, Kaycee M. Sink, Paul K. Whelton, Jackson T. Wright, Jan Basile, Srinivasan Beddhu, Udayan Bhatt, Tara I. Chang, Glenn M. Chertow, Michel Chonchol, Barry I. Freedman, William Haley, Joachim H. Ix, Lois A. Katz, Anthony A. Killeen, Vasilios Papademetriou, Ana C. Ricardo, Karen Servilla, Barry Wall, Dawn Wolfgram, Jerry Yee

Nephrology Articles

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of(intensive group;

Incidence, Risks, And Types Of Infections In Pediatric Long-Term Care Facilities, Lisa Saiman, Philip Maykowski, Meghan Murray, Bevin Cohen, Natalie Neu, Gordon R. Hutcheon, Elaine Larson

NYMC Faculty Publications

Importance: The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects.

Objectives: To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs).

Design, Setting, and Participants: This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from …

Efficacy And Safety Of Spironolactone In Acute Heart Failure: The Athena-Hf Randomized Clinical Trial., Javed Butler, Kevin J. Anstrom, G. Michael Felker, Michael M. Givertz, Andreas P Kalogeropoulos, Marvin A. Konstam, Douglas L. Mann, Kenneth B. Margulies, Steven E Mcnulty, Robert J. Mentz, Margaret M. Redfield, W.H. Wilson Tang, David J. Whellan, Monica Shah, Patrice Desvigne-Nickens, Adrian F. Hernandez, Eugene Braunwald

Department of Medicine Faculty Papers

Importance: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF.

Objective: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone.

Design, Setting, and Participants: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone and had …

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) …

Pathway Of Protection: Ethnic Identity, Self-Esteem, And Substance Use Among Multiracial Youth, Sycarah Fisher, Tamika C. B. Zapolski, Chelsea Sheehan, Jessica Barnes-Najor

Educational, School, and Counseling Psychology Faculty Publications

Fifty percent of adolescents have tried an illicit drug and 70% have tried alcohol by the end of high school, with even higher rates among multiracial youth. Ethnic identity is a protective factor against substance use for minority groups. However, little is known about the mechanisms that facilitate its protective effects, and even less is known about this relationship for multiracial youth. The purpose of the present study was to examine the protective effect of ethnic identity on substance use and to determine whether this relationship operated indirectly through self-esteem, a strong predictor of substance use for among adolescent populations. …

The Prognostic Importance Of Scalp Location In Primary Head And Neck Melanoma., Junko Ozao-Choy, Daniel W Nelson, Jason Hiles, Stacey L Stern, Jeong Lim Yoon, Myung Shin Sim, Mark Faries

Articles, Abstracts, and Reports

BACKGROUND AND OBJECTIVES: For patients with cutaneous melanoma, primary tumors located in the head and neck is associated with poor outcomes. The reason for this difference and whether it is applicable to all locations within the head and neck remains unclear. We hypothesized that scalp melanoma is uniquely distinguished from other anatomic sites and is independently responsible for the poor prognosis of head and neck melanoma.

METHODS: Query and analysis of a prospectively maintained melanoma database of all patients treated for primary cutaneous melanoma from 1971 to 2010.

RESULTS: Of 11 384 patients identified, 7% (n = 799) of lesions …

Effects Of Socioeconomic Status On Children With Well-Differentiated Thyroid Cancer., Evan F Garner, Ilan I Maizlin, Matthew B Dellinger, Kenneth W Gow, Melanie Goldfarb, Adam B Goldin, John J Doski, Monica Langer, Jed G Nuchtern, Sanjeev A Vasudevan, Mehul V Raval, Elizabeth A Beierle

Articles, Abstracts, and Reports

BACKGROUND: Well-differentiated thyroid cancer is the most common endocrine malignancy in children. Adult literature has demonstrated socioeconomic disparities in patients undergoing thyroidectomy, but the effects of socioeconomic status on the management of pediatric well-differentiated thyroid cancer remains poorly understood.

METHODS: Patients ≤21 years of age with well-differentiated thyroid cancer remains were reviewed from the National Cancer Data Base. Three socioeconomic surrogate variables were identified: insurance type, median income, and educational quartile. Tumor characteristics, diagnostic intervals, and clinical outcomes were compared within each socioeconomic surrogate variable.

RESULTS: A total of 9,585 children with well-differentiated thyroid cancer remains were reviewed. In multivariate …

The Natural History Of Severe Acute Liver Injury., David G Koch, J L Speiser, V Durkalski, R J Fontana, T Davern, B Mcguire, R T Stravitz, A M Larson, I Liou, Oren K Fix, M L Schilsky, T Mccashland, J E Hay, N Murray, O S Shaikh, D Ganger, A Zaman, S B Han, R T Chung, R S Brown, S Munoz, K R Reddy, L Rossaro, R Satyanarayana, A J Hanje, J Olson, R M Subramanian, C Karvellas, B Hameed, A H Sherker, W M Lee, A Reuben

Articles, Abstracts, and Reports

OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death.

METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × …

Other Tobacco Product Use Among Sexual Minority Young Adult Bar Patrons, Amanda Fallin-Bennett, Nadra E. Lisha, Pamela M. Ling

Nursing Faculty Publications

Introduction—Lesbian, gay, and bisexual (LGB) individuals smoke at rates 1.5–2 times higher than the general population, but less is known about LGB consumption of other tobacco products (OTPs) and gender differences. OTP use among young adult LGB bar patrons and the relationship among past quit attempts, intention to quit, and binge drinking with OTP use was examined.

Methods—A cross-sectional survey of young adults (aged 18–26) in bars/nightclubs in seven U.S. cities between 2012 and 2014 (N=8,010; 1,101 LGB participants) was analyzed in 2016. Logistic regressions examined current use of five OTPs (cigarillos, electronic cigarettes, hookah, chewing tobacco, and …

Advertising Exposure And Use Of E-Cigarettes Among Female Current And Former Tobacco Users Of Childbearing Age, Kristin Ashford, Emily Rayens, Amanda T. Wiggins, Mary Kay Rayens, Amanda Fallin-Bennett, Molly Malany Sayre

Nursing Faculty Publications

Objective: The study examined the relationship between exposure to e‐cigarette advertising and e‐cigarette use by pregnancy status, including use of flavored e‐cigarette products, among women of childbearing age.

Design: A cross‐sectional, correlational design was used.

Subjects: Female current or former tobacco users in Central and Eastern Kentucky, 18–45 years old (N = 194, 52% pregnant).

Measures: Demographics, pregnancy status, cigarette and e‐cigarette use, and exposure to e‐cigarette advertising.

Results: Younger age, white non‐Hispanic race, and greater exposure to e‐cigarette advertising were associated with a higher likelihood of ever using e‐cigarettes (p < .05 for each variable). Pregnancy was not associated with ever use (p = .11). Younger age was associated …

Ibrutinib Unmasks Critical Role Of Bruton Tyrosine Kinase In Primary Cns Lymphoma., Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S. Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Dan Rohle, Marc Rosenblum, Agnes Viale, Viviane S. Tabar, Cameron W. Brennan, Igor T. Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Antonio Omuro, Elena Pentsova, Alissa A. Thomas, Elina Tsyvkin, Ariela Noy, M. Lia Palomba, Paul Hamlin, Craig S. Sauter, Craig H. Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C. Lallana, Vaios Hatzoglou, Anne S. Reiner, Philip H. Gutin, Jason T. Huse, Katherine S. Panageas, Thomas G. Graeber, Nikolaus Schultz, Lisa M. Deangelis, Ingo K. Mellinghoff

Department of Neurology Faculty Papers

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated …

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 …

Increasing Use Of Allogeneic Hematopoietic Cell Transplantation In Patients Aged 70 Years And Older In The United States, Lori Muffly, Marcelo C. Pasquini, Michael Martens, Ruta Brazauskas, Xiaochun Zhu, Kehinde Adekola, Mahmoud Aljurf, Karen K. Ballen, Ashish Bajel, Frederic Baron, Minoo Battiwalla, Amer Beitinjaneh, Jean-Yves Cahn, Mathew Carabasi, Yi-Bin Chen, Saurabh Chhabra, Stefan Ciurea, Edward Copelan, Anita D'Souza, John Edwards, James Foran, Cesar O. Freytes, Henry C. Fung, Robert Peter Gale, Sergio Giralt, Shahrukh K. Hashmi, Gerhard C. Hildebrandt, Vincent Ho, Ann Jakubowski, Hillard Lazarus

Internal Medicine Faculty Publications

In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥ 70 years with hematologic malignancies across the United States. Adults ≥ 70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥ 70 years underwent HCT across 103 transplant centers. The number and proportion of allografts …

Pulmonary Tumor Embolism Secondary To Soft Tissue And Bone Sarcomas: A Case Report And Literature Review., Nicholas Latchana, Vincent C Daniel, Robert W Gould, Raphael E Pollock

Oncology Articles

BACKGROUND: Tumor embolisms (TE) are an underappreciated source of pulmonary embolisms in sarcoma. Most evidence in the literature is limited to case reports and none have described the presence of TE secondary to myxofibrosarcoma. We report the first case of myxofibrosarcoma TE and perform a review of the literature for TE secondary to bone and soft tissue sarcomas (STS).

CASE PRESENTATION: A 36-year-old female presented with debilitating pain of the right upper extremity secondary to a recurrent soft tissue sarcoma. She had distant metastasis to the lung. An MRI revealed a 25-cm shoulder mass involving the proximal arm muscles with …

Effect Of Natriuretic Peptide-Guided Therapy On Hospitalization Or Cardiovascular Mortality In High-Risk Patients With Heart Failure And Reduced Ejection Fraction: A Randomized Clinical Trial., G. Michael Felker, Kevin J. Anstrom, Kirkwood F. Adams, Justin A Ezekowitz, Mona Fiuzat, Nancy Houston-Miller, James L. Januzzi, Daniel B. Mark, Ileana L. Piña, Gayle Passmore, David J. Whellan, Hongqiu Yang, Lawton S. Cooper, Eric S. Leifer, Patrice Desvigne-Nickens, Christopher M O'Connor

Department of Medicine Faculty Papers

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results.

Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF).

Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in …

Tia1 Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia Promote Phase Separation And Alter Stress Granule Dynamics., Ian R. Mackenzie, Alexandra M. Nicholson, Mohona Sarkar, James Messing, Maria D. Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B. Perkerson, Aishe Kurti, Billie J. Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R. Hsiung, Charles Krieger, Melissa E. Murray, Masato Kato, John D. Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A. Zivkovic, Veronica Hirsch-Reinshagen, Raymond P. Roos, Stephan Züchner, Neill R. Graff-Radford, Ronald C. Petersen, Richard J. Caselli, Zbigniew K. Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W. Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B. Boylan, J. Paul Taylor, Rosa Rademakers

Department of Neurology Faculty Papers

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10

Interleukin-6 (Il-6) Rs1800796 And Cyclin Dependent Kinase Inhibitor (Cdkn2a/Cdkn2b) Rs2383207 Are Associated With Ischemic Stroke In Indigenous West African Men, Rufus Akinyemi, Donna K. Arnett, Hemant K. Tiwari, Bruce Ovbiagele, Fred Sarfo, Vinodh Srinivasasainagendra, Marguerite Ryan Irvin, Abiodun Adeoye, Rodney T. Perry, Albert Akpalu, Carolyn Jenkins, Lukman Owolabi, Reginald Obiako, Kolawole Wahab, Emmanuel Sanya, Morenikeji Komolafe, Michael Fawale, Philip Adebayo, Godwin Osaigbovo, Taofiki Sunmonu, Paul Olowoyo, Innocent Chukwuonye, Yahaya Obiabo, Onoja Akpa, Sylvia Melikam, Raelle Saulson, Raj Kalaria, Adesola Ogunniyi, Mayowa Owolabi

Epidemiology and Environmental Health Faculty Publications

Background—Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub – Saharan African populations. Interleukin–6 polymorphisms have been previously associated with ischemic stroke in some non-African populations.

Aim—Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6 and CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study.

Methods—Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known …

Abl Kinase Regulation By Braf/Erk And Cooperation With Akt In Melanoma, Aditi Jain, Rakshamani Tripathi, Courtney P. Turpin, Chi Wang, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

The melanoma incidence continues to increase, and the disease remains incurable for many due to its metastatic nature and high rate of therapeutic resistance. In particular, melanomas harboring BRAF^V600E and PTEN mutations often are resistant to current therapies, including BRAF inhibitors (BRAFi) and immune checkpoint inhibitors. Abl kinases (Abl/Arg) are activated in melanomas and drive progression; however, their mechanism of activation has not been established. Here we elucidate a novel link between BRAF^V600E/ERK signaling and Abl kinases. We demonstrate that BRAF^V600E/ERK play a critical role in binding, phosphorylating and regulating Abl localization and Abl/Arg activation …

In Vivo Study Of Plasmodium Falciparum Chloroquine Susceptibility In Three Departments Of Haiti, Christian P. Raccurt, Philippe Brasseur, Micheline Cicéron, Dana M. Parke, Marcus J. Zervos, Jacques Boncy

Global Health Initiative Articles

BACKGROUND: Malaria is considered a public health priority in Haiti, with a goal to eliminate by year 2020. Chloroquine is the first-line treatment recommended by the Ministry of Public Health and Population. In order to verify the suitability of chloroquine for uncomplicated malaria treatment, an in vivo study of susceptibility of Plasmodium falciparum to chloroquine was conducted from January 2013 to March 2015 in six localities in the south of Haiti.

RESULTS: Sixty-one patients who presented with confirmed P. falciparum malaria were included in the study and followed until day 28 after having taken 25 mg/kg of chloroquine orally over …

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 …

Mindfulness-Based Stress Reduction In Women With Overweight Or Obesity: A Randomized Clinical Trial., Nazia Raja-Khan, Katrina Agito, Julie Shah, Christy M Stetter, Theresa S Gustafson, Holly Socolow, Allen R Kunselman, Diane K. Reibel, Richard S Legro

Marcus Institute of Integrative Health Faculty Papers

OBJECTIVE: To evaluate the feasibility and cardiometabolic effects of mindfulness-based stress reduction (MBSR) in women with overweight or obesity.

METHODS: Eighty-six women with BMI ≥ 25 kg/m

RESULTS: Compared to health education, the MBSR group demonstrated significantly improved mindfulness at 8 weeks (mean change from baseline, 4.5 vs. -1.0; P = 0.03) and significantly decreased perceived stress at 16 weeks (-3.6 vs. -1.3, P = 0.01). In the MBSR group, there were significant reductions in fasting glucose at 8 weeks (-8.9 mg/dL, P = 0.02) and at 16 weeks (-9.3 mg/dL, P = 0.02) compared to baseline. Fasting glucose did …

Substance Use Disorders, Violence, Mental Health, And Hiv: Differentiating A Syndemic Factor By Gender And Sexuality, Kiyomi Tsuyuki, Eileen V. Pitpitan, Maria A. Levi-Minzi, Lianne A. Urada, Steven P. Kurtz, Jamila K. Stockman, Hilary L. Surratt

Center for Health Services Research Faculty Publications

This paper measures syndemic substance use disorder, violence, and mental health and compares the syndemic among HIV-infected heterosexual men, heterosexual women, and men who have sex with men (MSM). Data were from a sample of high needs substance-using, HIV-infected people in South Florida between 2010 and 2012 (n = 481). We used confirmatory factor analysis to measure a syndemic latent variable and applied measurement invariance models to identify group differences in the data structure of syndemic co-morbidities among heterosexual men, heterosexual women, and MSM. We found that variables used to measure the syndemic fit each sub-group, supporting that substance use …