Open Access. Powered by Scholars. Published by Universities.®

Digital Commons Network™

Open Access. Powered by Scholars. Published by Universities.®

Humans

Discipline
Institution
Publication Year
Publication
Publication Type
File Type

Articles 23581 - 23610 of 28618

Full-Text Articles in Entire DC Network

Building A Bridge Between Genetics And Outcomes Research: Application In Autism (The Autgo Study)., Zohreh Talebizadeh, Ayten Shah, Pcori Eain-2419 Working Group Aug 2018

Building A Bridge Between Genetics And Outcomes Research: Application In Autism (The Autgo Study)., Zohreh Talebizadeh, Ayten Shah, Pcori Eain-2419 Working Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Concerns over the need to improve translational aspects of genetics research studies and engaging community members in the research process have been noted in the literature and raised by patient advocates. In addition to the work done by patient advocacy groups, organizations such as the Patient-Centered Outcomes Research Institute advocate for a change in the culture of research from being researcher-driven to becoming more patient-driven.

OBJECTIVE: Our project, Autism Genetics and Outcomes (AutGO), consists of two phases. The goal for phase I was to initiate a general discussion around the main topic (i.e., linking genetics and outcomes research). We …


The Effect Of Lowering Public Insurance Income Limits On Hospitalizations For Low-Income Children., Jessica L. Bettenhausen, Matt Hall, Jeffrey D. Colvin, Henry T. Puls, Paul J. Chung Aug 2018

The Effect Of Lowering Public Insurance Income Limits On Hospitalizations For Low-Income Children., Jessica L. Bettenhausen, Matt Hall, Jeffrey D. Colvin, Henry T. Puls, Paul J. Chung

Manuscripts, Articles, Book Chapters and Other Papers

Background and objectives: Thirty million children are currently covered by public insurance; however, the future funding and structure of public insurance are uncertain. Our objective was to determine the number, estimated costs, and demographic characteristics of hospitalizations that would become ineligible for public insurance reimbursement under 3 federal poverty level (FPL) eligibility scenarios.

Methods: In this retrospective cohort study using the 2014 State Inpatient Databases, we included all pediatric (age

Results: In 775 460 publicly reimbursed hospitalizations in 14 states, reductions in eligibility limits to 300%, 200%, or 100% of the FPL would have resulted in large numbers of newly …


Influenza-Associated Parotitis During The 2014-2015 Influenza Season In The United States., Melissa A. Rolfes, Alexander J. Millman, Pamela Talley, Lina I. Elbadawi, Natalie A. Kramer, Joh R. Barnes, Lenee Blanton, Jeffrey P. Davis, Stefanie Cole, John J. Dreisig, Rebecca Garten, Thomas Haupt, Mary Anne Jackson, Anna Kocharian, Daniel Leifer, Ruth Lynfield, Karen Martin, Lisa Mchugh, Sara Robinson, George Turabelidze, Lori A. Webber, Meghan Pearce Weinberg, David E. Wentworth, Lyn Finelli, Michael A. Jhung Aug 2018

Influenza-Associated Parotitis During The 2014-2015 Influenza Season In The United States., Melissa A. Rolfes, Alexander J. Millman, Pamela Talley, Lina I. Elbadawi, Natalie A. Kramer, Joh R. Barnes, Lenee Blanton, Jeffrey P. Davis, Stefanie Cole, John J. Dreisig, Rebecca Garten, Thomas Haupt, Mary Anne Jackson, Anna Kocharian, Daniel Leifer, Ruth Lynfield, Karen Martin, Lisa Mchugh, Sara Robinson, George Turabelidze, Lori A. Webber, Meghan Pearce Weinberg, David E. Wentworth, Lyn Finelli, Michael A. Jhung

Manuscripts, Articles, Book Chapters and Other Papers

Background: During the 2014-2015 influenza season in the United States, 256 cases of influenza-associated parotitis were reported from 27 states. We conducted a case-control study and laboratory investigation to further describe this rare clinical manifestation of influenza.

Methods: During February 2015-April 2015, we interviewed 50 cases (with parotitis) and 124 ill controls (without parotitis) with laboratory-confirmed influenza; participants resided in 11 states and were matched by age, state, hospital admission status, and specimen collection date. Influenza viruses were characterized using real-time polymerase chain reaction and next-generation sequencing. We compared cases and controls using conditional logistic regression. Specimens from additional reported …


Technoference: Longitudinal Associations Between Parent Technology Use, Parenting Stress, And Child Behavior Problems., Brandon T. Mcdaniel Phd, Jenny S Radesky Aug 2018

Technoference: Longitudinal Associations Between Parent Technology Use, Parenting Stress, And Child Behavior Problems., Brandon T. Mcdaniel Phd, Jenny S Radesky

Health Services and Informatics Research

BACKGROUND AND OBJECTIVES: Heavy parent digital technology use has been associated with suboptimal parent-child interactions and internalizing/externalizing child behavior, but directionality of associations is unclear. This study aims to investigate longitudinal bidirectional associations between parent technology use and child behavior, and understand whether this is mediated by parenting stress.

METHODS: Participants included 183 couples with a young child (age 0-5 years, mean = 3.0 years) who completed surveys at baseline, 1, 3 and 6 months. Cross-lagged structural equation models of parent technology interference during parent-child activities, parenting stress, and child externalizing and internalizing behavior were tested.

RESULTS: Controlling for potential …


Meta-Analysis Of The Incidence And Patterns Of Second Neoplasms After Photon Craniospinal Irradiation In Children With Medulloblastoma, Abhishek Bavle, Sayani Tewari, Amy Sisson, Murali Chintagumpala, Michael Anderson, Arnold C Paulino Aug 2018

Meta-Analysis Of The Incidence And Patterns Of Second Neoplasms After Photon Craniospinal Irradiation In Children With Medulloblastoma, Abhishek Bavle, Sayani Tewari, Amy Sisson, Murali Chintagumpala, Michael Anderson, Arnold C Paulino

Library Staff Publications

BACKGROUND: Second neoplasms (SNs) are a well-established long-term adverse effect of radiation therapy (RT), but there are limited data regarding their incidence and location relative to the radiation field, specific to medulloblastoma (MB) survivors after craniospinal irradiation (CSI).

METHODS: A systematic literature review, per Preferred Reporting Items for Systematic Reviews and Meta-Analyses, identified six studies reporting the incidence and locations of SNs for 1,114 patients with MB, after CSI, with a median follow-up of ∼9 years (7.6-15.4 years). The study-specific cumulative incidence (CI) of SNs, second benign neoplasms (SBNs), and second malignant neoplasms (SMNs) were standardized to a 10-year time …


Myocardial Dysfunction After Out-Of-Hospital Cardiac Arrest: Predictors And Prognostic Implications., Yuan Yao, Nicholas James Johnson, Sarah Muirhead Perman, Vimal Ramjee, Anne Victoria Grossestreuer, David Foster Gaieski Aug 2018

Myocardial Dysfunction After Out-Of-Hospital Cardiac Arrest: Predictors And Prognostic Implications., Yuan Yao, Nicholas James Johnson, Sarah Muirhead Perman, Vimal Ramjee, Anne Victoria Grossestreuer, David Foster Gaieski

Department of Emergency Medicine Faculty Papers

We aim to determine the incidence of early myocardial dysfunction after out-of-hospital cardiac arrest, risk factors associated with its development, and association with outcome. A retrospective chart review was performed among consecutive out-of-hospital cardiac arrest (OHCA) patients who underwent echocardiography within 24 h of return of spontaneous circulation at three urban teaching hospitals. Our primary outcome is early myocardial dysfunction, defined as a left ventricular ejection fraction < 40% on initial echocardiogram. We also determine risk factors associated with myocardial dysfunction using multivariate analysis, and examine its association with survival and neurologic outcome. A total of 190 patients achieved ROSC and underwent echocardiography within 24 h. Of these, 83 (44%) patients had myocardial dysfunction. A total of 37 (45%) patients with myocardial dysfunction survived to discharge, 39% with intact neurologic status. History of congestive heart failure (OR 6.21; 95% CI 2.54-15.19), male gender (OR 2.27; 95% CI 1.08-4.78), witnessed arrest (OR 4.20; 95% CI 1.78-9.93), more than three doses of epinephrine (OR 6.10; 95% CI 1.12-33.14), more than four defibrillations (OR 4.7; 95% CI 1.35-16.43), longer duration of resuscitation (OR 1.06; 95% CI 1.01-1.10), and therapeutic hypothermia (OR 3.93; 95% CI 1.32-11.75) were associated with myocardial dysfunction. Cardiopulmonary resuscitation immediately initiated by healthcare personnel was associated with lower odds of myocardial dysfunction (OR 0.40; 95% CI 0.17-0.97). There was no association between early myocardial dysfunction and mortality or neurological outcome. Nearly half of OHCA patients have myocardial dysfunction. A number of clinical factors are associated with myocardial dysfunction, and may aid providers in anticipating which patients need early diagnostic evaluation and specific treatments. Early myocardial dysfunction is not associated with neurologically intact survival.


Genetic Testing In Cardiovascular Medicine, Ali J Marian Aug 2018

Genetic Testing In Cardiovascular Medicine, Ali J Marian

The Texas Heart Institute Journal

No abstract provided.


Prognostic Performance Of Prospective Versus Retrospective Electrocardiographic Gating In Coronary Computed Tomographic Angiography, Pradnya Velankar, Kongkiat Chaikriangkrai, Ninad Dewal, Sayf Khaleel Bala, Belqis Elferjani, Sama Alchalabi, Su Min Chang Aug 2018

Prognostic Performance Of Prospective Versus Retrospective Electrocardiographic Gating In Coronary Computed Tomographic Angiography, Pradnya Velankar, Kongkiat Chaikriangkrai, Ninad Dewal, Sayf Khaleel Bala, Belqis Elferjani, Sama Alchalabi, Su Min Chang

The Texas Heart Institute Journal

Coronary computed tomographic angiography (CCTA) with prospective electrocardiographic gating reduces radiation exposure, but its prognostic power for predicting cardiovascular risk in patients with suspected CAD has not been fully validated. To determine whether prospective gating performs as well as retrospective gating in this population, we compared these scan modes in patients undergoing 64-slice CCTA.

From January 2009 through September 2011, 1,407 patients underwent CCTA; of these, 915 (mean age, 57.8 ± 13.5 yr; 54% male) had suspected coronary artery disease at the time of CCTA and were included in the study. Prospective gating was used in 195 (21%) and retrospective …


Physician Burnout: Causes, Consequences, And (?) Cures, Herbert L Fred, Mark S Scheid Aug 2018

Physician Burnout: Causes, Consequences, And (?) Cures, Herbert L Fred, Mark S Scheid

The Texas Heart Institute Journal

No abstract provided.


Sex-Related Differences In Outcomes Of Thoracic Organ Transplantation And Mechanical Circulatory Support, Daoud Daoud, Faisal H Cheema, Jeffrey A Morgan, Gabriel Loor Aug 2018

Sex-Related Differences In Outcomes Of Thoracic Organ Transplantation And Mechanical Circulatory Support, Daoud Daoud, Faisal H Cheema, Jeffrey A Morgan, Gabriel Loor

The Texas Heart Institute Journal

No abstract provided.


High-Risk Cardiovascular Conditions In Sports-Related Sudden Death: Prevalence In 5,169 Schoolchildren Screened Via Cardiac Magnetic Resonance, Paolo Angelini, Benjamin Y Cheong, Veronica V Lenge De Rosen, Alberto Lopez, Carlo Uribe, Anthony H Masso, Syed W Ali, Barry R Davis, Raja Muthupillai, James T Willerson Aug 2018

High-Risk Cardiovascular Conditions In Sports-Related Sudden Death: Prevalence In 5,169 Schoolchildren Screened Via Cardiac Magnetic Resonance, Paolo Angelini, Benjamin Y Cheong, Veronica V Lenge De Rosen, Alberto Lopez, Carlo Uribe, Anthony H Masso, Syed W Ali, Barry R Davis, Raja Muthupillai, James T Willerson

The Texas Heart Institute Journal

Improving preparticipation screening of candidates for sports necessitates establishing the prevalence of high-risk cardiovascular conditions (hr-CVC) that predispose young people to sudden cardiac death (SCD). Our accurate, novel protocol chiefly involved the use of cardiac magnetic resonance (CMR) to estimate this prevalence.

Middle and high school students from a general United States population were screened by means of questionnaires, resting electrocardiograms, and CMR to determine the prevalence of 3 types of hr-CVC: electrocardiographic abnormalities, cardiomyopathies, and anomalous coronary artery origin from the opposite sinus with intramural coronary course (ACAOS-IM). We examined the range of normal left ventricular size and function …


A Novel Fas-Binding Outer Membrane Protein And Lipopolysaccharide Of Leptospira Interrogans Induce Macrophage Apoptosis Through The Fas/Fasl-Caspase-8/-3 Pathway., Peng Du, Shi-Jun Li, David M. Ojcius, Kai-Xuan Li, Wei-Lin Hu, Xu'ai Lin, Ai-Hua Sun, Jie Yan Jul 2018

A Novel Fas-Binding Outer Membrane Protein And Lipopolysaccharide Of Leptospira Interrogans Induce Macrophage Apoptosis Through The Fas/Fasl-Caspase-8/-3 Pathway., Peng Du, Shi-Jun Li, David M. Ojcius, Kai-Xuan Li, Wei-Lin Hu, Xu'ai Lin, Ai-Hua Sun, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Leptospira interrogans is the major causative agent of leptospirosis, an emerging, globally spreading zoonotic infectious disease. The pathogen induces macrophage apoptosis, but the molecular basis and mechanism remain unknown. In the present study, we found that L. interrogans caused apoptosis of phagocytosis-inhibited macrophages, and the product of the L. interrogans LB047 gene (Lep-OMP047) was the unique protein captured by mouse and human Fas proteins. The recombinant expressed Lep-OMP047 (rLep-OMP047) strongly bound mouse and human Fas proteins with equilibrium association constant (K


Apoptosis Signal-Regulating Kinase 1 Inhibition Attenuates Human Airway Smooth Muscle Growth And Migration In Chronic Obstructive Pulmonary Disease., Mathew S. Eapen, Anudeep Kota, Howard Vindin, Kielan D. Mcalinden, Dia Xenaki, Brian G. Oliver, Deepak A. Deshpande, Sukhwinder Singh Sohal, Pawan Sharma Jul 2018

Apoptosis Signal-Regulating Kinase 1 Inhibition Attenuates Human Airway Smooth Muscle Growth And Migration In Chronic Obstructive Pulmonary Disease., Mathew S. Eapen, Anudeep Kota, Howard Vindin, Kielan D. Mcalinden, Dia Xenaki, Brian G. Oliver, Deepak A. Deshpande, Sukhwinder Singh Sohal, Pawan Sharma

Center for Translational Medicine Faculty Papers

Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro. …


Association Between Bone-Specific Physical Activity Scores And Pqct-Derived Measures Of Bone Strength And Geometry In Healthy Young And Middle-Aged Premenopausal Women., Sojung Kim, Breanne S Baker, Pragya Sharma-Ghimire, Debra A Bemben, Michael G Bemben Jul 2018

Association Between Bone-Specific Physical Activity Scores And Pqct-Derived Measures Of Bone Strength And Geometry In Healthy Young And Middle-Aged Premenopausal Women., Sojung Kim, Breanne S Baker, Pragya Sharma-Ghimire, Debra A Bemben, Michael G Bemben

College of Science & Mathematics Departmental Research

The aim of this study was to determine if bone-specific physical activity questionnaire (BPAQ) scores were positively related to bone health in healthy young and middle-aged premenopausal women. The total BPAQ was a stronger predictor of bone strength and bone mineral density of hip in young women as compared to middle-aged premenopausal women.

PURPOSE: The purpose of this study was to determine whether the BPAQ scores were predictive indices of volumetric BMD (vBMD), bone strength, and bone geometry in young and middle-aged premenopausal women.

METHODS: Healthy young (n = 60) and middle-aged premenopausal women (n = 54) between the ages …


Evolution Of Cortical Neurogenesis In Amniotes Controlled By Robo Signaling Levels., Adrián Cárdenas, Ana Villalba, Camino De Juan Romero, Esther Picó, Christina Kyrousi, Athanasia C Tzika, Marc Tessier-Lavigne, Le Ma, Micha Drukker, Silvia Cappello, Víctor Borrell Jul 2018

Evolution Of Cortical Neurogenesis In Amniotes Controlled By Robo Signaling Levels., Adrián Cárdenas, Ana Villalba, Camino De Juan Romero, Esther Picó, Christina Kyrousi, Athanasia C Tzika, Marc Tessier-Lavigne, Le Ma, Micha Drukker, Silvia Cappello, Víctor Borrell

Department of Neuroscience Faculty Papers

Cerebral cortex size differs dramatically between reptiles, birds, and mammals, owing to developmental differences in neuron production. In mammals, signaling pathways regulating neurogenesis have been identified, but genetic differences behind their evolution across amniotes remain unknown. We show that direct neurogenesis from radial glia cells, with limited neuron production, dominates the avian, reptilian, and mammalian paleocortex, whereas in the evolutionarily recent mammalian neocortex, most neurogenesis is indirect via basal progenitors. Gain- and loss-of-function experiments in mouse, chick, and snake embryos and in human cerebral organoids demonstrate that high Slit/Robo and low Dll1 signaling, via Jag1 and Jag2, are necessary and …


Site-1 Protease Deficiency Causes Human Skeletal Dysplasia Due To Defective Inter-Organelle Protein Trafficking, Yuji Kondo, Debabrata Patra, Et Al Jul 2018

Site-1 Protease Deficiency Causes Human Skeletal Dysplasia Due To Defective Inter-Organelle Protein Trafficking, Yuji Kondo, Debabrata Patra, Et Al

Open Access Publications

Site-1 protease (S1P), encoded by MBTPS1, is a serine protease in the Golgi. S1P regulates lipogenesis, endoplasmic reticulum (ER) function, and lysosome biogenesis in mice and in cultured cells. However, how S1P differentially regulates these diverse functions in humans has been unclear. In addition, no human disease with S1P deficiency has been identified. Here, we report a pediatric patient with an amorphic and a severely hypomorphic mutation in MBTPS1. The unique combination of these mutations results in a frequency of functional MBTPS1 transcripts of approximately 1%, a finding that is associated with skeletal dysplasia and elevated blood lysosomal enzymes. We …


Human Fibroblast And Stem Cell Resource From The Dominantly Inherited Alzheimer Network, Celeste M Karch, Damián Hernández, Jen-Chyong Wang, Jacob Marsh, Alex W Hewitt, Simon Hsu, Joanne Norton, Denise Levitch, Tamara Donahue, Wendy Sigurdson, Bernardino Ghetti, Martin Farlow, Jasmeer Chhatwal, Sarah Berman, Carlos Cruchaga, John C Morris, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Alice Pébay, Alison M Goate Jul 2018

Human Fibroblast And Stem Cell Resource From The Dominantly Inherited Alzheimer Network, Celeste M Karch, Damián Hernández, Jen-Chyong Wang, Jacob Marsh, Alex W Hewitt, Simon Hsu, Joanne Norton, Denise Levitch, Tamara Donahue, Wendy Sigurdson, Bernardino Ghetti, Martin Farlow, Jasmeer Chhatwal, Sarah Berman, Carlos Cruchaga, John C Morris, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Alice Pébay, Alison M Goate

Open Access Publications

BACKGROUND: Mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) cause autosomal dominant forms of Alzheimer disease (ADAD). More than 280 pathogenic mutations have been reported in APP, PSEN1, and PSEN2. However, understanding of the basic biological mechanisms that drive the disease are limited. The Dominantly Inherited Alzheimer Network (DIAN) is an international observational study of APP, PSEN1, and PSEN2 mutation carriers with the goal of determining the sequence of changes in presymptomatic mutation carriers who are destined to develop Alzheimer disease.

RESULTS: We generated a library of 98 dermal fibroblast lines from 42 ADAD families …


Plasticity Of Differentiated Cells In Wound Repair And Tumorigenesis, Part I: Stomach And Pancreas, Joseph Burclaff, Jason C Mills Jul 2018

Plasticity Of Differentiated Cells In Wound Repair And Tumorigenesis, Part I: Stomach And Pancreas, Joseph Burclaff, Jason C Mills

Open Access Publications

For the last century or so, the mature, differentiated cells throughout the body have been regarded as largely inert with respect to their regenerative potential, yet recent research shows that they can become progenitor-like and re-enter the cell cycle. Indeed, we recently proposed that mature cells can become regenerative via a conserved set of molecular mechanisms ('paligenosis'), suggesting that a program for regeneration exists alongside programs for death (apoptosis) and division (mitosis). In two Reviews describing how emerging concepts of cellular plasticity are changing how the field views regeneration and tumorigenesis, we present the commonalities in the molecular and cellular …


Beta1pix Exchange Factor Stabilizes The Ubiquitin Ligase Nedd4-2 And Plays A Critical Role In Enac Regulation By Ampk In Kidney Epithelial Cells, Pei-Yin Ho, Hui Li, Tengis S. Pavlov, Roland D. Tuerk, Diego Tabares, René Brunisholz, Dietbert Neumann, Alexander Staruschenko, Kenneth R. Hallows Jul 2018

Beta1pix Exchange Factor Stabilizes The Ubiquitin Ligase Nedd4-2 And Plays A Critical Role In Enac Regulation By Ampk In Kidney Epithelial Cells, Pei-Yin Ho, Hui Li, Tengis S. Pavlov, Roland D. Tuerk, Diego Tabares, René Brunisholz, Dietbert Neumann, Alexander Staruschenko, Kenneth R. Hallows

Hypertension and Vascular Research Articles

Our previous work has established that the metabolic sensor AMP-activated protein kinase (AMPK) inhibits the epithelial Na+ channel (ENaC) by promoting its binding to neural precursor cell-expressed, developmentally down-regulated 4-2, E3 ubiquitin protein ligase (Nedd4-2). Here, using MS analysis and in vitro phosphorylation, we show that AMPK phosphorylates Nedd4-2 at the Ser-444 (Xenopus Nedd4-2) site critical for Nedd4-2 stability. We further demonstrate that the Pak-interacting exchange factor β1Pix is required for AMPK-mediated inhibition of ENaC-dependent currents in both CHO and murine kidney cortical collecting duct (CCD) cells. Short hairpin RNA-mediated knockdown of β1Pix expression in CCD cells attenuated the …


Oscillometry And Pulmonary Mri Measurements Of Ventilation Heterogeneity In Obstructive Lung Disease: Relationship To Quality Of Life And Disease Control, Heather M Young, Fumin Guo, Rachel L Eddy, Geoffrey Maksym, Grace Parraga Jul 2018

Oscillometry And Pulmonary Mri Measurements Of Ventilation Heterogeneity In Obstructive Lung Disease: Relationship To Quality Of Life And Disease Control, Heather M Young, Fumin Guo, Rachel L Eddy, Geoffrey Maksym, Grace Parraga

Medical Biophysics Publications

Ventilation heterogeneity is a hallmark finding in obstructive lung disease and may be evaluated using a variety of methods, including multiple-breath gas washout and pulmonary imaging. Such methods provide an opportunity to better understand the relationships between structural and functional abnormalities in the lungs, and their relationships with important clinical outcomes. We measured ventilation heterogeneity and respiratory impedance in 100 subjects [50 patients with asthma, 22 ex-smokers, and 28 patients with chronic obstructive pulmonary disease (COPD)] using oscillometry and hyperpolarized


Discovery And Validation Of Autosomal Dominant Alzheimer's Disease Mutations, Simon Hsu, Brian A Gordon, Russ Hornbeck, Joanne B Norton, Denise Levitch, Adia Louden, Ellen Ziegemeier, Robert Laforce, Jasmeer Chhatwal, Gregory S Day, Eric Mcdade, John C Morris, Anne M Fagan, Tammie L S Benzinger, Alison M Goate, Carlos Cruchaga, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Celeste M Karch Jul 2018

Discovery And Validation Of Autosomal Dominant Alzheimer's Disease Mutations, Simon Hsu, Brian A Gordon, Russ Hornbeck, Joanne B Norton, Denise Levitch, Adia Louden, Ellen Ziegemeier, Robert Laforce, Jasmeer Chhatwal, Gregory S Day, Eric Mcdade, John C Morris, Anne M Fagan, Tammie L S Benzinger, Alison M Goate, Carlos Cruchaga, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Celeste M Karch

Open Access Publications

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. Mutations in amyloid-β precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the pathogenic cause of autosomal dominant AD (ADAD). However, polymorphisms also exist within these genes.

METHODS: In order to distinguish polymorphisms from pathogenic mutations, the DIAN Expanded Registry has implemented an algorithm for determining ADAD pathogenicity using available information from multiple domains, including genetic, bioinformatic, clinical, imaging, and biofluid measures and in vitro analyses.

RESULTS: We propose that PSEN1 M84V, PSEN1 A396T, PSEN2 R284G, and APP T719N are likely pathogenic …


Antimalarial Proteasome Inhibitor Reveals Collateral Sensitivity From Intersubunit Interactions And Fitness Cost Of Resistance., Laura A. Kirkman, Wenhu Zhan, Joseph Visone, Alexis Dziedziech, Pradeep K. Singh, Hao Fan, Xinran Tong, Igor Bruzual, Ryoma Hara, Masanori Kawasaki, Toshihiro Imaeda, Rei Okamoto, Kenjiro Sato, Mayako Michino, Elena Fernandez Alvaro, Liselle F. Guiang, Laura M. Sanz, Daniel J. Mota, Kavitha Govindasamy, Rong Wang, Yan Ling, Patrick K. Tumwebaze, George Sukenick, Lei Shi, Jeremie Vendome, Purnima Bhanot, Philip J. Rosenthal, Kazuyoshi Aso, Michael A. Foley, Roland A. Cooper, Bjorn Kafsack, J Stone Doggett, Carl F. Nathan, Gang Lin Jul 2018

Antimalarial Proteasome Inhibitor Reveals Collateral Sensitivity From Intersubunit Interactions And Fitness Cost Of Resistance., Laura A. Kirkman, Wenhu Zhan, Joseph Visone, Alexis Dziedziech, Pradeep K. Singh, Hao Fan, Xinran Tong, Igor Bruzual, Ryoma Hara, Masanori Kawasaki, Toshihiro Imaeda, Rei Okamoto, Kenjiro Sato, Mayako Michino, Elena Fernandez Alvaro, Liselle F. Guiang, Laura M. Sanz, Daniel J. Mota, Kavitha Govindasamy, Rong Wang, Yan Ling, Patrick K. Tumwebaze, George Sukenick, Lei Shi, Jeremie Vendome, Purnima Bhanot, Philip J. Rosenthal, Kazuyoshi Aso, Michael A. Foley, Roland A. Cooper, Bjorn Kafsack, J Stone Doggett, Carl F. Nathan, Gang Lin

Natural Sciences and Mathematics | Faculty Scholarship

We describe noncovalent, reversible asparagine ethylenediamine (AsnEDA) inhibitors of the Plasmodium falciparum proteasome (Pf20S) β5 subunit that spare all active subunits of human constitutive and immuno-proteasomes. The compounds are active against erythrocytic, sexual, and liver-stage parasites, against parasites resistant to current antimalarials, and against P. falciparum strains from patients in Africa. The β5 inhibitors synergize with a β2 inhibitor in vitro and in mice and with artemisinin. P. falciparum selected for resistance to an AsnEDA β5 inhibitor surprisingly harbored a point mutation in the noncatalytic β6 subunit. The β6 mutant was resistant to the species-selective Pf20S β5 inhibitor but remained …


Novel Management Strategies For Medically-Refractory Vasospasm Following Aneurysmal Subarachnoid Hemorrhage, Fawaz Al-Mufti, Krishna Amuluru, Nitesh Damodara, Mohammad El-Ghanem, Rolla Nuoman, Naveed Kamal, Sarmad Al-Marsoummi, Nicholas A. Morris, Neha S. Dangayach, Stephan A. Mayer Jul 2018

Novel Management Strategies For Medically-Refractory Vasospasm Following Aneurysmal Subarachnoid Hemorrhage, Fawaz Al-Mufti, Krishna Amuluru, Nitesh Damodara, Mohammad El-Ghanem, Rolla Nuoman, Naveed Kamal, Sarmad Al-Marsoummi, Nicholas A. Morris, Neha S. Dangayach, Stephan A. Mayer

Neurology Articles

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is an important cause of further morbidity and mortality after an already devastating condition. Though traditionally attributed to vasospasm of large capacitance arteries and the resulting down-stream disruption of cerebral blood flow, the pathogenesis of DCI has proven to be more complex with early brain injury, blood-brain barrier disruption, microthrombosis, cortical spreading depolarizations, and the failure of cerebral autoregulation as newly elucidated factors. Vasospasm is a known consequence of SAH. The standard of care includes close monitoring for neurological deterioration, most often with serial clinical examinations, transcranial Doppler ultrasonography, and vascular …


Co-Expression Of Cd39 And Cd103 Identifies Tumor-Reactive Cd8 T Cells In Human Solid Tumors., Thomas Duhen, Rebekka Duhen, Ryan Montler, Jake Moses, Tarsem Moudgil, Noel F De Miranda, Cheri P Goodall, Tiffany C Blair, Bernard A Fox, Jason E Mcdermott, Shu-Ching Chang, Gary Grunkemeier, Rom Leidner, Richard Bryan Bell, Andrew D Weinberg Jul 2018

Co-Expression Of Cd39 And Cd103 Identifies Tumor-Reactive Cd8 T Cells In Human Solid Tumors., Thomas Duhen, Rebekka Duhen, Ryan Montler, Jake Moses, Tarsem Moudgil, Noel F De Miranda, Cheri P Goodall, Tiffany C Blair, Bernard A Fox, Jason E Mcdermott, Shu-Ching Chang, Gary Grunkemeier, Rom Leidner, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies of CD103+CD39+ CD8 …


Recurrent Tumor-Specific Regulation Of Alternative Polyadenylation Of Cancer-Related Genes., Zhuyi Xue, René L Warren, Ewan A Gibb, Daniel Macmillan, Johnathan Wong, Readman Chiu, S Austin Hammond, Chen Yang, Ka Ming Nip, Catherine A Ennis, Abigail Hahn, Sheila Reynolds, Inanc Birol Jul 2018

Recurrent Tumor-Specific Regulation Of Alternative Polyadenylation Of Cancer-Related Genes., Zhuyi Xue, René L Warren, Ewan A Gibb, Daniel Macmillan, Johnathan Wong, Readman Chiu, S Austin Hammond, Chen Yang, Ka Ming Nip, Catherine A Ennis, Abigail Hahn, Sheila Reynolds, Inanc Birol

Articles, Abstracts, and Reports

BACKGROUND: Alternative polyadenylation (APA) results in messenger RNA molecules with different 3' untranslated regions (3' UTRs), affecting the molecules' stability, localization, and translation. APA is pervasive and implicated in cancer. Earlier reports on APA focused on 3' UTR length modifications and commonly characterized APA events as 3' UTR shortening or lengthening. However, such characterization oversimplifies the processing of 3' ends of transcripts and fails to adequately describe the various scenarios we observe.

RESULTS: We built a cloud-based targeted de novo transcript assembly and analysis pipeline that incorporates our previously developed cleavage site prediction tool, KLEAT. We applied this pipeline to …


Hepatic Tristetraprolin Promotes Insulin Resistance Through Rna Destabilization Of Fgf21, Konrad T. Sawicki, Hsiang-Chun Chang, Jason S. Shapiro, Marina Bayeva, Adam De Jesus, Brian N. Finck, Jason A. Wertheim, Perry J. Blackshear, Hossein Ardehali Jul 2018

Hepatic Tristetraprolin Promotes Insulin Resistance Through Rna Destabilization Of Fgf21, Konrad T. Sawicki, Hsiang-Chun Chang, Jason S. Shapiro, Marina Bayeva, Adam De Jesus, Brian N. Finck, Jason A. Wertheim, Perry J. Blackshear, Hossein Ardehali

Open Access Publications

The role of posttranscriptional metabolic gene regulatory programs in diabetes is not well understood. Here, we show that the RNA-binding protein tristetraprolin (TTP) is reduced in the livers of diabetic mice and humans and is transcriptionally induced in response to insulin treatment in murine livers in vitro and in vivo. Liver-specific Ttp-KO (lsTtp-KO) mice challenged with high-fat diet (HFD) have improved glucose tolerance and peripheral insulin sensitivity compared with littermate controls. Analysis of secreted hepatic factors demonstrated that fibroblast growth factor 21 (FGF21) is posttranscriptionally repressed by TTP. Consistent with increased FGF21, lsTtp-KO mice fed HFD have increased brown fat …


Association Of Inferior Vena Cava Filter Placement For Venous Thromboembolic Disease And A Contraindication To Anticoagulation With 30-Day Mortality, Tyson E. Turner, Mohammed J. Saeed, Eric Novak, David L. Brown Jul 2018

Association Of Inferior Vena Cava Filter Placement For Venous Thromboembolic Disease And A Contraindication To Anticoagulation With 30-Day Mortality, Tyson E. Turner, Mohammed J. Saeed, Eric Novak, David L. Brown

Open Access Publications

Importance: Despite the absence of data from randomized clinical trials, professional societies recommend inferior vena cava (IVC) filters for patients with venous thromboembolic disease (VTE) and a contraindication to anticoagulation therapy. Prior observational studies of IVC filters have suggested a mortality benefit associated with IVC filter insertion but have often failed to adjust for immortal time bias, which is the time before IVC filter insertion, during which death can only occur in the control group.

Objective: To determine the association of IVC filter placement with 30-day mortality after adjustment for immortal time bias.

Design, Setting, and Participants: This comparative effectiveness, …


The Effect Of Abnormal Vitamin D Levels In Athletes., Jakub Sikora-Klak, Steven J Narvy, Justin Yang, Eric Makhni, F Daniel Kharrazi, Nima Mehran Jul 2018

The Effect Of Abnormal Vitamin D Levels In Athletes., Jakub Sikora-Klak, Steven J Narvy, Justin Yang, Eric Makhni, F Daniel Kharrazi, Nima Mehran

Articles, Abstracts, and Reports

Vitamin D is a lipophilic prohormone integral to musculoskeletal, autoimmune, oncologic, cardiovascular, and mental health. Of particular importance to the orthopedic surgeon is the role of vitamin D in the regulation of bone mass, muscle strength, and physical performance. Although vitamin D-related skeletal pathologies are rare in industrialized nations, emerging research in the field has shown that most American adults have inadequate levels of vitamin D. Even among athletes, there is a high prevalence of vitamin D deficiency, which may place competitors at risk of stress fractures, illness, and delayed muscle recovery. Adequately identifying vitamin D-deficient individuals in need of …


Development Of Igrow: A Curriculum For Youth/Adult Dyads To Increase Gardening Skills, Culinary Competence, And Family Meal Time For Youths And Their Adult Caregivers, Jade A White, Rebecca L Hagedorn, Nicole L. Waterland, Makenzie L. Barr, Oluremi A Famodu, Amy E. Root, Adrienne A. White, Sarah E. Colby, Lisa Franzen-Castle, Kendra Kattelmann, Melissa D. Olfert Jul 2018

Development Of Igrow: A Curriculum For Youth/Adult Dyads To Increase Gardening Skills, Culinary Competence, And Family Meal Time For Youths And Their Adult Caregivers, Jade A White, Rebecca L Hagedorn, Nicole L. Waterland, Makenzie L. Barr, Oluremi A Famodu, Amy E. Root, Adrienne A. White, Sarah E. Colby, Lisa Franzen-Castle, Kendra Kattelmann, Melissa D. Olfert

Health and Nutritional Sciences Faculty Publications

This manuscript describes the development of a “learn by actively participating” curriculum for youth and their adult caregivers (dyad pair) to increase gardening skills, culinary competence, and family meal time. The curriculum was developed by integrating “iCook 4-H” and Junior Masters Gardener “Health and Nutrition from the Garden”, and “Essential Elements of 4-H Youth Development” curriculums with additional resources for gardening activities from the USDA’s My Plate and garden-based recipes. Expert reviewers (n = 11) provided feedback on the curriculum content, session structure, dosage, age appropriateness, and balance of the three focused areas. Seven family dyads (n = 14) participated …


Supervision In Community Mental Health: Understanding Intensity Of Ebt Focus., Leah Lucid, Rosemary Meza, Michael D Pullmann, Nathaniel Jungbluth, Esther Deblinger, Shannon Dorsey Jul 2018

Supervision In Community Mental Health: Understanding Intensity Of Ebt Focus., Leah Lucid, Rosemary Meza, Michael D Pullmann, Nathaniel Jungbluth, Esther Deblinger, Shannon Dorsey

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The goal of the present study was to examine clinician, supervisor, and organizational factors that are associated with the intensity of evidence-based treatment (EBT) focus in workplace-based clinical supervision of a specific EBT, Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). Supervisors (n = 56) and clinicians (n = 207) from mental health organizations across Washington State completed online self-report questionnaires. Multilevel modeling (MLM) analyses were used to examine the relative influence of nested clinician and supervisor factors on the intensity of EBT focus in supervision. We found that 33% of the variance in clinician report of EBT supervision intensity clustered at the …