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Improving Behavioral Health Workforce Supply And Needs Estimates Using Active Surveillance Data, Shinobu Watanabe-Galloway, Li-Wu Chen, Kate Trout, David Palm, Marlene Deras, Zaeema Naveed Jan 2019

Improving Behavioral Health Workforce Supply And Needs Estimates Using Active Surveillance Data, Shinobu Watanabe-Galloway, Li-Wu Chen, Kate Trout, David Palm, Marlene Deras, Zaeema Naveed

Journal Articles: Epidemiology

INTRODUCTION: Previous studies show that supply of behavioral health professionals in rural areas is inadequate to meet the need. Measuring shortage using licensure data on psychiatrists is a common approach. Although inexpensive, the licensure data have many limitations. An alternative is to implement an active surveillance system, which uses licensure data in addition to active data collection to obtain timely and detailed information.

METHODS: Nebraska Health Professions Tracking Service (HPTS) data were used to examine differences in workforce supply estimates between the passive (licensure data only) and active (HPTS data) surveillance systems. The impact of these differences on the designation …


Hiv Viral Rebound Due To A Possible Drug-Drug Interaction Between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide And Calcium-Containing Products: Report Of 2 Cases, S. Lena Kang-Birken, Dena El-Sayed, John Prichard Jan 2019

Hiv Viral Rebound Due To A Possible Drug-Drug Interaction Between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide And Calcium-Containing Products: Report Of 2 Cases, S. Lena Kang-Birken, Dena El-Sayed, John Prichard

School of Pharmacy Faculty Articles

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a potent fixed-dose, once-daily regimen for HIV-1 treatment and has rare emergence of drug resistance. We report a potential drug-drug interaction in 2 female patients both receiving treatment for HIV and cerebral toxoplasmosis: one case between E/C/F/TAF with calcium carbonate and a second case involving leucovorin as calcium salt. Both cases resulted in rise in HIV RNA levels and emergence of M184 V mutation and resistance to elvitegravir and raltegravir. To the best of our knowledge, these 2 cases are the first reports of rapid emergence of mutation from coadministration of E/C/F/TAF and calcium.


Responsible, Safe, And Effective Use Of Biologics In The Management Of Low Back Pain: American Society Of Interventional Pain Physicians (Asipp) Guidelines, Annu Navani, Laxmaiah Manchikanti, Sheri L. Albers, Richard E. Latchaw, Jaya Sanapati, Alan David Kaye, Sairam Atluri, Sheldon Jordan, Ashim Gupta, David Cedeno, Alejandro Vallejo, Bert Fellows, Nebojsa Nick Knezevic, Miguel Pappolla, Sudhir Diwan, Andrea M. Trescot, Amol Soin, Adam M. Kaye, Steve M. Aydin, Aaron K. Calodney, Kenneth D. Candido, Sanjay Bakshi, Ramsin M. Benyamin, Ricardo Vallejo, Art Watanabe, Douglas Beall, Todd P. Stitik, Patrick M. Foye, Erik M. Helander, Joshua A. Hirsch Jan 2019

Responsible, Safe, And Effective Use Of Biologics In The Management Of Low Back Pain: American Society Of Interventional Pain Physicians (Asipp) Guidelines, Annu Navani, Laxmaiah Manchikanti, Sheri L. Albers, Richard E. Latchaw, Jaya Sanapati, Alan David Kaye, Sairam Atluri, Sheldon Jordan, Ashim Gupta, David Cedeno, Alejandro Vallejo, Bert Fellows, Nebojsa Nick Knezevic, Miguel Pappolla, Sudhir Diwan, Andrea M. Trescot, Amol Soin, Adam M. Kaye, Steve M. Aydin, Aaron K. Calodney, Kenneth D. Candido, Sanjay Bakshi, Ramsin M. Benyamin, Ricardo Vallejo, Art Watanabe, Douglas Beall, Todd P. Stitik, Patrick M. Foye, Erik M. Helander, Joshua A. Hirsch

School of Pharmacy Faculty Articles

BACKGROUND: Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public …


Serological Proteomic Screening And Evaluation Of A Recombinant Egg Antigen For The Diagnosis Of Low-Intensity Schistosoma Mansoni Infections In Endemic Area In Brazil, Vanessa Silva-Moraes, Lisa Marie Shollenberger, William Castro-Borges, Ana Lucia Teles Rabello, Donald A. Harn, Lia Carolina Soares Medeiros, Wander De Jesus Jeremias, Liliane Maria Vidal Siqueira, Caroline Stephane Salviano Pereira, Maria Luysa Camargos Pedrosa, Nathalie Bonatti Franco Almeida, Aureo Almeida, Jose Roberto Lambertucci, Nidia Francisca De Figueiredo Carneiro, Paulo Marcos Zech Coelho, Refaella Fortini Queiroz Grenfell Jan 2019

Serological Proteomic Screening And Evaluation Of A Recombinant Egg Antigen For The Diagnosis Of Low-Intensity Schistosoma Mansoni Infections In Endemic Area In Brazil, Vanessa Silva-Moraes, Lisa Marie Shollenberger, William Castro-Borges, Ana Lucia Teles Rabello, Donald A. Harn, Lia Carolina Soares Medeiros, Wander De Jesus Jeremias, Liliane Maria Vidal Siqueira, Caroline Stephane Salviano Pereira, Maria Luysa Camargos Pedrosa, Nathalie Bonatti Franco Almeida, Aureo Almeida, Jose Roberto Lambertucci, Nidia Francisca De Figueiredo Carneiro, Paulo Marcos Zech Coelho, Refaella Fortini Queiroz Grenfell

Biological Sciences Faculty Publications

Background

Despite decades of use of control programs, schistosomiasis remains a global public health problem. To further reduce prevalence and intensity of infection, or to achieve the goal of elimination in low-endemic areas, there needs to be better diagnostic tools to detect low-intensity infections in low-endemic areas in Brazil. The rationale for development of new diagnostic tools is that the current standard test Kato-Katz (KK) is not sensitive enough to detect low-intensity infections in low-endemic areas. In order to develop new diagnostic tools, we employed a proteomics approach to identify biomarkers associated with schistosome-specific immune responses in hopes of developing …


Residential Household Yard Care Practices Along Urban-Exurban Gradients In Six Climatically-Diverse U.S. Metropolitan Areas, Dexter H. Locke, Colin Polsky, J. Morgan Grove, Peter M. Groffman, Kristen C. Nelson, Kelli L. Larson, Jeannine Cavender-Bares, James B. Heffernan, Rinku Roy Chowdhury, Sarah E. Hobbie, Neil D. Bettez, Sharon J. Hall, Christopher Neill, Laura Ogden, Jarlath O’Neil-Dunne Jan 2019

Residential Household Yard Care Practices Along Urban-Exurban Gradients In Six Climatically-Diverse U.S. Metropolitan Areas, Dexter H. Locke, Colin Polsky, J. Morgan Grove, Peter M. Groffman, Kristen C. Nelson, Kelli L. Larson, Jeannine Cavender-Bares, James B. Heffernan, Rinku Roy Chowdhury, Sarah E. Hobbie, Neil D. Bettez, Sharon J. Hall, Christopher Neill, Laura Ogden, Jarlath O’Neil-Dunne

Geography

Residential land is expanding in the United States, and lawn now covers more area than the country’s leading irrigated crop by area. Given that lawns are widespread across diverse climatic regions and there is rising concern about the environmental impacts associated with their management, there is a clear need to understand the geographic variation, drivers, and outcomes of common yard care practices. We hypothesized that 1) income, age, and the number of neighbors known by name will be positively associated with the odds of having irrigated, fertilized, or applied pesticides in the last year, 2) irrigation, fertilization, and pesticide application …


Disruption Of Immune Homeostasis In Human Dendritic Cells Via Regulation Of Autophagy And Apoptosis By Porphyromonas Gingivalis, Mohamed M Meghil, Omnia K Tawfik, Mahmoud Elashiry, Mythilypriya Rajendran, Roger M Arce, David J Fulton, Patricia V Schoenlein, Christopher W Cutler Jan 2019

Disruption Of Immune Homeostasis In Human Dendritic Cells Via Regulation Of Autophagy And Apoptosis By Porphyromonas Gingivalis, Mohamed M Meghil, Omnia K Tawfik, Mahmoud Elashiry, Mythilypriya Rajendran, Roger M Arce, David J Fulton, Patricia V Schoenlein, Christopher W Cutler

Faculty, Staff and Student Publications

As fundamental processes of immune homeostasis, autophagy, and apoptosis must be maintained to mitigate risk of chronic inflammation and autoimmune diseases. Periodontitis is a chronic inflammatory disease characterized by oral microbial dysbiosis, and dysregulation of dendritic cell (DC) and T cell responses. The aim of this study was to elucidate the underlying mechanisms by which the oral microbe


Gwas Of Qrs Duration Identifies New Loci Specific To Hispanic/Latino Populations, Brenton R Swenson, Tin Louie, Henry J Lin, Raúl Méndez-Giráldez, Jennifer E Below, Cathy C Laurie, Kathleen F Kerr, Heather Highland, Timothy A Thornton, Kelli K Ryckman, Charles Kooperberg, Elsayed Z Soliman, Amanda A Seyerle, Xiuqing Guo, Kent D Taylor, Jie Yao, Susan R Heckbert, Dawood Darbar, Lauren E Petty, Barbara Mcknight, Susan Cheng, Natalie A Bello, Eric A Whitsel, Craig L Hanis, Mike A Nalls, Daniel S Evans, Jerome I Rotter, Tamar Sofer, Christy L Avery, Nona Sotoodehnia Jan 2019

Gwas Of Qrs Duration Identifies New Loci Specific To Hispanic/Latino Populations, Brenton R Swenson, Tin Louie, Henry J Lin, Raúl Méndez-Giráldez, Jennifer E Below, Cathy C Laurie, Kathleen F Kerr, Heather Highland, Timothy A Thornton, Kelli K Ryckman, Charles Kooperberg, Elsayed Z Soliman, Amanda A Seyerle, Xiuqing Guo, Kent D Taylor, Jie Yao, Susan R Heckbert, Dawood Darbar, Lauren E Petty, Barbara Mcknight, Susan Cheng, Natalie A Bello, Eric A Whitsel, Craig L Hanis, Mike A Nalls, Daniel S Evans, Jerome I Rotter, Tamar Sofer, Christy L Avery, Nona Sotoodehnia

Faculty, Staff and Student Publications

BACKGROUND: The electrocardiographically quantified QRS duration measures ventricular depolarization and conduction. QRS prolongation has been associated with poor heart failure prognosis and cardiovascular mortality, including sudden death. While previous genome-wide association studies (GWAS) have identified 32 QRS SNPs across 26 loci among European, African, and Asian-descent populations, the genetics of QRS among Hispanics/Latinos has not been previously explored.

METHODS: We performed a GWAS of QRS duration among Hispanic/Latino ancestry populations (n = 15,124) from four studies using 1000 Genomes imputed genotype data (adjusted for age, sex, global ancestry, clinical and study-specific covariates). Study-specific results were combined using fixed-effects, inverse variance-weighted …


Towards Earlier Identification: Physicians Assistants' Perceptions Of Their Ability To Identify, Diagnose, And Refer Patients With Autism Spectrum Disorder., Denise Rizzolo, Noël E Smith, Timothy C. Mccall Jan 2019

Towards Earlier Identification: Physicians Assistants' Perceptions Of Their Ability To Identify, Diagnose, And Refer Patients With Autism Spectrum Disorder., Denise Rizzolo, Noël E Smith, Timothy C. Mccall

Clinical Research and Leadership Faculty Publications

No abstract provided.


A Pilot Study On The Kinetics Of Metabolites And Microvascular Cutaneous Effects Of Nitric Oxide Inhalation In Healthy Volunteers, Adriano R Tonelli, Kulwant S Aulak, Mostafa K Ahmed, Alfred Hausladen, Batool Abuhalimeh, Charlie J Casa, Stephen C Rogers, David Timm, Allan Doctor, Benjamin Gaston, Raed A Dweik Jan 2019

A Pilot Study On The Kinetics Of Metabolites And Microvascular Cutaneous Effects Of Nitric Oxide Inhalation In Healthy Volunteers, Adriano R Tonelli, Kulwant S Aulak, Mostafa K Ahmed, Alfred Hausladen, Batool Abuhalimeh, Charlie J Casa, Stephen C Rogers, David Timm, Allan Doctor, Benjamin Gaston, Raed A Dweik

Open Access Publications

RATIONALE: Inhaled nitric oxide (NO) exerts a variety of effects through metabolites and these play an important role in regulation of hemodynamics in the body. A detailed investigation into the generation of these metabolites has been overlooked.

OBJECTIVES: We investigated the kinetics of nitrite and S-nitrosothiol-hemoglobin (SNO-Hb) in plasma derived from inhaled NO subjects and how this modifies the cutaneous microvascular response.

FINDINGS: We enrolled 15 healthy volunteers. Plasma nitrite levels at baseline and during NO inhalation (15 minutes at 40 ppm) were 102 (86-118) and 114 (87-129) nM, respectively. The nitrite peak occurred at 5 minutes of discontinuing NO …


The Abcs Of Wheeze: Asthma And Bacterial Communities, Naomi G. Wilson, Ariel Hernandez-Leyva, Andrew L. Kau Jan 2019

The Abcs Of Wheeze: Asthma And Bacterial Communities, Naomi G. Wilson, Ariel Hernandez-Leyva, Andrew L. Kau

Open Access Publications

No abstract provided.


Embracing Differences To Improve Success: American Orthopaedic Association Presidential Address, Boston, Massachusetts, June 23, 2017: Aoa Critical Issues, Regis J O'Keefe Jan 2019

Embracing Differences To Improve Success: American Orthopaedic Association Presidential Address, Boston, Massachusetts, June 23, 2017: Aoa Critical Issues, Regis J O'Keefe

Open Access Publications

No abstract provided.


Dupilumab Improves Symptoms, Quality Of Life, And Productivity In Uncontrolled Persistent Asthma, Jonathan Corren, Mario Castro, Pascal Chanez, Leonardo Fabbri, Vijay N Joish, Nikhil Amin, Neil M H Graham, Vera Mastey, Adeline Abbé, Christine Taniou, Puneet Mahajan, Ariel Teper, Gianluca Pirozzi, Laurent Eckert Jan 2019

Dupilumab Improves Symptoms, Quality Of Life, And Productivity In Uncontrolled Persistent Asthma, Jonathan Corren, Mario Castro, Pascal Chanez, Leonardo Fabbri, Vijay N Joish, Nikhil Amin, Neil M H Graham, Vera Mastey, Adeline Abbé, Christine Taniou, Puneet Mahajan, Ariel Teper, Gianluca Pirozzi, Laurent Eckert

Open Access Publications

BACKGROUND: In a pivotal, phase 2b study (NCT01854047) in patients with uncontrolled persistent asthma, despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2 agonists, dupilumab improved lung function, reduced severe exacerbations, and showed an acceptable safety profile.

OBJECTIVE: To assess the impact of dupilumab on asthma control, symptoms, quality of life (QoL), and productivity.

METHODS: Data are shown for the intention-to-treat population receiving dupilumab 200/300 mg every 2 weeks (doses being assessed in phase 3; NCT02414854), or placebo. Predefined analyses of total scores were conducted at week 24 for the 5-item Asthma Control Questionnaire (ACQ-5), patient-reported morning/evening (AM/PM) asthma symptoms, Asthma …


Glioblastoma Treated With Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy: Safety, Efficacy, And Outcomes, Ashwin A. Kamath, Daniel D. Friedman, S Hassan A. Akbari, Albert H. Kim, Yu Tao, Jinqin Luo, Eric C. Leuthardt Jan 2019

Glioblastoma Treated With Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy: Safety, Efficacy, And Outcomes, Ashwin A. Kamath, Daniel D. Friedman, S Hassan A. Akbari, Albert H. Kim, Yu Tao, Jinqin Luo, Eric C. Leuthardt

Open Access Publications

BACKGROUND: Despite the multitude of available treatments, glioblastoma (GBM) remains an aggressive and uniformly fatal tumor. Laser interstitial thermal therapy (LITT) is a novel, minimally invasive treatment that holds promise for treating patients with GBM who are not candidates for traditional open craniotomy. However, due to the recent introduction of LITT into clinical practice, large series that evaluate safety and long-term outcomes after LITT are lacking.

OBJECTIVE: To present our institution's series of over 50 GBM patients treated with LITT, with regard to safety, efficacy, and outcomes.

METHODS: We performed a retrospective descriptive study of patients with histologically proven GBM …


Syndemic Effects Of Hiv Risk Behaviours: Results From The Nhanes Study, L Smith, C Cao, X Zong, D T Mcdermott, S Stefanac, S Haider, S E Jackson, N Veronese, G F López-Sánchez, A Koyanagi, L Yang, I Grabovac Jan 2019

Syndemic Effects Of Hiv Risk Behaviours: Results From The Nhanes Study, L Smith, C Cao, X Zong, D T Mcdermott, S Stefanac, S Haider, S E Jackson, N Veronese, G F López-Sánchez, A Koyanagi, L Yang, I Grabovac

Open Access Publications

The aim of the present study is to use the syndemic framework to investigate the risk of contracting HIV in the US population. Cross-sectional analyses are from The National Health and Nutrition Examination Survey. We extracted and aggregated data on HIV antibody test, socio-demographic characteristics, alcohol use, drug use, depression, sexual behaviours and sexually transmitted diseases from cycle 2009-2010 to 2015-2016. We carried out weighted regression among young adults (20-39 years) and adults (40-59 years) separately. In total, 5230 men and 5794 women aged 20-59 years were included in the present analyses. In total, 0.8% men and 0.2% women were …


Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges To Clinical Application, Henry Caplan, Scott D Olson, Akshita Kumar, Mitchell George, Karthik S Prabhakara, Pamela Wenzel, Supinder Bedi, Naama E Toledano-Furman, Fabio Triolo, Julian Kamhieh-Milz, Guido Moll, Charles S Cox Jan 2019

Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges To Clinical Application, Henry Caplan, Scott D Olson, Akshita Kumar, Mitchell George, Karthik S Prabhakara, Pamela Wenzel, Supinder Bedi, Naama E Toledano-Furman, Fabio Triolo, Julian Kamhieh-Milz, Guido Moll, Charles S Cox

Faculty, Staff and Student Publications

For several decades, multipotent mesenchymal stromal cells (MSCs) have been extensively studied for their therapeutic potential across a wide range of diseases. In the preclinical setting, MSCs demonstrate consistent ability to promote tissue healing, down-regulate excessive inflammation and improve outcomes in animal models. Several proposed mechanisms of action have been posited and demonstrated across an array of in vitro models. However, translation into clinical practice has proven considerably more difficult. A number of prominent well-funded late-phase clinical trials have failed, thus calling out for new efforts to optimize product delivery in the clinical setting. In this review, we discuss novel …


Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng Jan 2019

Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with an internal tandem duplication in Fms-related tyrosine kinase 3 (FLT3-ITD) is identified as a subgroup with poor outcome and intrinsic resistance to chemotherapy and therefore urgent need for development of novel therapeutic strategies.

Methods: The antitumor effects of melatonin alone or combined with sorafenib were evaluated via flow cytometry and immunoblotting assays in FLT-ITD AML cells. Also, the ex vivo and in vivo models were used to test the synergistic effects of melatonin and sorafenib against leukemia with FLT3/ITD mutation.

Results: Our study shows for the first time that melatonin inhibits proliferation and induces apoptosis …


Resting-State Functional Connectivity Of The Habenula In Mood Disorder Patients With And Without Suicide-Related Behaviors, Elisa Ambrosi, David B Arciniegas, Kaylah N Curtis, Michelle A Patriquin, Gianfranco Spalletta, Gabriele Sani, B Christopher Frueh, J Christopher Fowler, Alok Madan, Ramiro Salas Jan 2019

Resting-State Functional Connectivity Of The Habenula In Mood Disorder Patients With And Without Suicide-Related Behaviors, Elisa Ambrosi, David B Arciniegas, Kaylah N Curtis, Michelle A Patriquin, Gianfranco Spalletta, Gabriele Sani, B Christopher Frueh, J Christopher Fowler, Alok Madan, Ramiro Salas

Staff and Researcher Publications

The habenula is a small midbrain structure that is important for brain signaling and learning from negative events. Thus, the habenula is strongly connected to both the reward system and motor regions. Increasing evidence suggests a role for the habenula in the etiology of psychiatric disorders, including mood and substance use disorders. However, no studies to date have investigated habenular resting-state functional connectivity (rsFC) in suicide-related behaviors (SB). The authors enrolled 123 individuals with major depressive disorder (MDD) or bipolar disorder and a history of suicide-related behaviors (SB+), 74 individuals with MDD or bipolar disorder and a history of suicidal …


Treatment Of Nightmares In Psychiatric Inpatients With Imagery Rehearsal Therapy: An Open Trial And Case Series, Thomas E Ellis, Katrina A Rufino, Michael R Nadorff Jan 2019

Treatment Of Nightmares In Psychiatric Inpatients With Imagery Rehearsal Therapy: An Open Trial And Case Series, Thomas E Ellis, Katrina A Rufino, Michael R Nadorff

Staff and Researcher Publications

Objectives: This study sought to assess the utility of Imagery Rehearsal Therapy (IRT) for nightmares in an inpatient psychiatric setting. Although IRT enjoys a substantial evidence base for efficacy in various populations, data with psychiatric inpatients are lacking.

Participants: Participants were 20 adult psychiatric inpatients (11 male, 9 female; mean age=43.4), in an extended stay psychiatric inpatient facility. All participants were diagnosed with multiple, treatment resistant, comorbid conditions, including mood disorders, anxiety disorders, personality disorders, and substance-related disorders. Patients with active psychosis or significant cognitive impairment were excluded.

Methods: This was an open trial utilizing a case series design. In …


Time-To-Event Analysis For Sports Injury Research Part 1: Time-Varying Exposures, Rasmus Oestergaard Nielsen, Michael Lejbach Bertelsen, Daniel Ramskov, Merete Møller, Adam Hulme, Daniel Theisen, Caroline F. Finch, Lauren Victoria Fortington, Mohammad Ali Mansournia, Erik Thorlund Parner Jan 2019

Time-To-Event Analysis For Sports Injury Research Part 1: Time-Varying Exposures, Rasmus Oestergaard Nielsen, Michael Lejbach Bertelsen, Daniel Ramskov, Merete Møller, Adam Hulme, Daniel Theisen, Caroline F. Finch, Lauren Victoria Fortington, Mohammad Ali Mansournia, Erik Thorlund Parner

Research outputs 2014 to 2021

BACKGROUND: ‘How much change in training load is too much before injury is sustained, among different athletes?’ is a key question in sports medicine and sports science. To address this question the investigator/practitioner must analyse exposure variables that change over time, such as change in training load. Very few studies have included time-varying exposures (eg, training load) and time-varying effect-measure modifiers (eg, previous injury, biomechanics, sleep/stress) when studying sports injury aetiology.

AIM: To discuss advanced statistical methods suitable for the complex analysis of time-varying exposures such as changes in training load and injury-related outcomes.

CONTENT: Time-varying exposures and time-varying effect-measure …


Modeling Cell Line-Specific Recruitment Of Signaling Proteins To The Insulin-Like Growth Factor 1 Receptor, Keesha E. Erickson, Dipak Barua, For Full List Of Authors, See Publisher's Website. Jan 2019

Modeling Cell Line-Specific Recruitment Of Signaling Proteins To The Insulin-Like Growth Factor 1 Receptor, Keesha E. Erickson, Dipak Barua, For Full List Of Authors, See Publisher's Website.

Chemical and Biochemical Engineering Faculty Research & Creative Works

Receptor tyrosine kinases (RTKs) typically contain multiple autophosphorylation sites in their cytoplasmic domains. Once activated, these autophosphorylation sites can recruit downstream signaling proteins containing Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains, which recognize phosphotyrosine-containing short linear motifs (SLiMs). These domains and SLiMs have polyspecific or promiscuous binding activities. Thus, multiple signaling proteins may compete for binding to a common SLiM and vice versa. To investigate the effects of competition on RTK signaling, we used a rule-based modeling approach to develop and analyze models for ligand-induced recruitment of SH2/PTB domain-containing proteins to autophosphorylation sites in the insulin-like growth factor 1 …


Patients' Perceptions And Patient-Reported Outcomes In Progressive-Fibrosing Interstitial Lung Diseases, Jeffrey J. Swigris, Kevin K. Brown, Rayid Abdulqawi, Ketan Buch, Daniel F. Dilling, Dirk Koschel, Krishna Thavarajah, Rade Tomic, Yoshikazu Inoue Dec 2018

Patients' Perceptions And Patient-Reported Outcomes In Progressive-Fibrosing Interstitial Lung Diseases, Jeffrey J. Swigris, Kevin K. Brown, Rayid Abdulqawi, Ketan Buch, Daniel F. Dilling, Dirk Koschel, Krishna Thavarajah, Rade Tomic, Yoshikazu Inoue

Internal Medicine Faculty Publications

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be …


A Herpesvirus Encoded Qa-1 Mimic Inhibits Natural Killer Cell Cytotoxicity Through Cd94/Nkg2a Receptor Engagement, Xiaoli Wang, Sytse J. Piersma, Christopher A. Nelson, Ya-Nan Dai, Ted Christensen, Eric Lazear, Liping Yang, Marjolein Sluijter, Thorbald Van Hall, Ted H. Hansen, Wayne M. Yokoyama, Daved H. Fremont Dec 2018

A Herpesvirus Encoded Qa-1 Mimic Inhibits Natural Killer Cell Cytotoxicity Through Cd94/Nkg2a Receptor Engagement, Xiaoli Wang, Sytse J. Piersma, Christopher A. Nelson, Ya-Nan Dai, Ted Christensen, Eric Lazear, Liping Yang, Marjolein Sluijter, Thorbald Van Hall, Ted H. Hansen, Wayne M. Yokoyama, Daved H. Fremont

Open Access Publications

A recurrent theme in viral immune evasion is the sabotage of MHC-I antigen presentation, which brings virus the concomitant issue of 'missing-self' recognition by NK cells that use inhibitory receptors to detect surface MHC-I proteins. Here, we report that rodent herpesvirus Peru (RHVP) encodes a Qa-1 like protein (pQa-1) via RNA splicing to counteract NK activation. While pQa-1 surface expression is stabilized by the same canonical peptides presented by murine Qa-1, pQa-1 is GPI-anchored and resistant to the activity of RHVP pK3, a ubiquitin ligase that targets MHC-I for degradation. pQa-1 tetramer staining indicates that it recognizes CD94/NKG2A receptors. Consistently, …


Resveratrol Attenuates Allergic Asthma And Associated Inflammation In The Lungs Through Regulation Of Mirna-34a That Targets Foxp3 In Mice, Esraah Alharris, Hasan Alghetaa, Ratanesh K. Seth, Saurabh Chatterjee, Narendra P. Singh, Mitzi Nagarkatti, Prakash Nagarkatti Dec 2018

Resveratrol Attenuates Allergic Asthma And Associated Inflammation In The Lungs Through Regulation Of Mirna-34a That Targets Foxp3 In Mice, Esraah Alharris, Hasan Alghetaa, Ratanesh K. Seth, Saurabh Chatterjee, Narendra P. Singh, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty Publications

Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At …


Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser Dec 2018

Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser

Internal Medicine Faculty Publications

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related …


Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu Dec 2018

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …


Trevo 2000: Results Of A Large Real-World Registry For Stent Retriever For Acute Ischemic Stroke., Mandy J Binning, Bruno Bartolini, Blaise Baxter, Ronald Budzik, Joey English, Rishi Gupta, Hirad Hedayat, Antonin Krajina, David Liebeskind, Raul G Nogueira, Ryan Shields, Erol Veznedaroglu Dec 2018

Trevo 2000: Results Of A Large Real-World Registry For Stent Retriever For Acute Ischemic Stroke., Mandy J Binning, Bruno Bartolini, Blaise Baxter, Ronald Budzik, Joey English, Rishi Gupta, Hirad Hedayat, Antonin Krajina, David Liebeskind, Raul G Nogueira, Ryan Shields, Erol Veznedaroglu

OhioHealth Research Institute Articles

Background Recent randomized controlled trials show benefit of thrombectomy for large vessel occlusion in stroke. Real-world data aid in assessing reproducibility of outcomes outside of clinical trials. The Trevo Retriever Registry is a multicenter, international, prospective study designed to assess outcomes in a large cohort of patients. Methods and Results The Trevo Registry is a prospective database of patients with large vessel occlusion treated with the Trevo device as the first device. The primary end point is revascularization based on modified Thrombolysis in Cerebral Infarction score and secondary end points include 90-day modified Rankin Scale, 90-day mortality, neurological deterioration at …


Precision Of Provider Licensure Data For Mapping Member Accessibility To Medicaid Managed Care Provider Networks, Nathaniel Bell, Ana Lòpez-Defede, Rebecca Wilkerson, Kathy Mayfield-Smith Dec 2018

Precision Of Provider Licensure Data For Mapping Member Accessibility To Medicaid Managed Care Provider Networks, Nathaniel Bell, Ana Lòpez-Defede, Rebecca Wilkerson, Kathy Mayfield-Smith

Faculty Publications

BACKGROUND:

In July 2018, the Centers for Medicare and Medicaid Services (CMS) updated its Medicaid Managed Care (MMC) regulations that govern network and access standards for enrollees. There have been few published studies of whether there is accurate geographic information on primary care providers to monitor network adequacy.

METHODS:

We analyzed a sample of nurse practitioner (NP) and physician address data registered in the state labor, licensing, and regulation (LLR) boards and the National Provider Index (NPI) using employment location data contained in the patient-centered medical home (PCMH) data file. Our main outcome measures were address discordance (%) at the …


Rare But Recurrent Ros1 Fusions Resulting From Chromosome 6q22 Microdeletions Are Targetable Oncogenes In Glioma., Monika A Davare, Jacob J Henderson, Anupriya Agarwal, Jacob P Wagner, Sudarshan R Iyer, Nameeta Shah, Randy Woltjer, Romel Somwar, Stephen W Gilheeney, Ana Decarvalo, Tom Mikkelson, Erwin G Van Meir, Marc Ladanyi, Brian J Druker Dec 2018

Rare But Recurrent Ros1 Fusions Resulting From Chromosome 6q22 Microdeletions Are Targetable Oncogenes In Glioma., Monika A Davare, Jacob J Henderson, Anupriya Agarwal, Jacob P Wagner, Sudarshan R Iyer, Nameeta Shah, Randy Woltjer, Romel Somwar, Stephen W Gilheeney, Ana Decarvalo, Tom Mikkelson, Erwin G Van Meir, Marc Ladanyi, Brian J Druker

Articles, Abstracts, and Reports

PURPOSE: Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.

EXPERIMENTAL DESIGN: Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset. Functional validation of the oncogenic potential and inhibitory sensitivity of discovered ROS1 fusions was performed using three independent cell-based model systems, and an

RESULTS:

CONCLUSIONS: Our findings highlight that CNS tumors should be specifically interrogated for these rare intrachromosomal 6q22 microdeletion …


Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu Dec 2018

Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu

Biostatistics Faculty Publications

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults > 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. …


Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude Dec 2018

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …