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Structural Basis For The Homotypic Fusion Of Chlamydial Inclusions By The Snare-Like Protein Inca., Gino Cingolani, Michael Mccauley, Anna Lobley, Alexander J Bryer, Jordan Wesolowski, Deanna L Greco, Ravi K Lokareddy, Erik Ronzone, Juan R Perilla, Fabienne Paumet Jun 2019

Structural Basis For The Homotypic Fusion Of Chlamydial Inclusions By The Snare-Like Protein Inca., Gino Cingolani, Michael Mccauley, Anna Lobley, Alexander J Bryer, Jordan Wesolowski, Deanna L Greco, Ravi K Lokareddy, Erik Ronzone, Juan R Perilla, Fabienne Paumet

Department of Biochemistry and Molecular Biology Faculty Papers

Many intracellular bacteria, including Chlamydia, establish a parasitic membrane-bound organelle inside the host cell that is essential for the bacteria's survival. Chlamydia trachomatis forms inclusions that are decorated with poorly characterized membrane proteins known as Incs. The prototypical Inc, called IncA, enhances Chlamydia pathogenicity by promoting the homotypic fusion of inclusions and shares structural and functional similarity to eukaryotic SNAREs. Here, we present the atomic structure of the cytoplasmic domain of IncA, which reveals a non-canonical four-helix bundle. Structure-based mutagenesis, molecular dynamics simulation, and functional cellular assays identify an intramolecular clamp that is essential for IncA-mediated homotypic membrane fusion during …


Intracellular Retention Of Mutant Lysyl Oxidase Leads To Aortic Dilation In Response To Increased Hemodynamic Stress, Vivian S Lee, Carmen M Halabi, Thomas J Broekelmann, Philip C Trackman, Nathan O Stitziel, Robert P Mecham Jun 2019

Intracellular Retention Of Mutant Lysyl Oxidase Leads To Aortic Dilation In Response To Increased Hemodynamic Stress, Vivian S Lee, Carmen M Halabi, Thomas J Broekelmann, Philip C Trackman, Nathan O Stitziel, Robert P Mecham

Open Access Publications

Heterozygous missense mutations in lysyl oxidase (LOX) are associated with thoracic aortic aneurysms and dissections. To assess how LOX mutations modify protein function and lead to aortic disease, we studied the factors that influence the onset and progression of vascular aneurysms in mice bearing a Lox mutation (p.M292R) linked to aortic dilation in humans. We show that mice heterozygous for the M292R mutation did not develop aneurysmal disease unless challenged with increased hemodynamic stress. Vessel dilation was confined to the ascending aorta although both the ascending and descending aortae showed changes in vessel wall structure, smooth muscle cell number and …


Points-To-Consider On The Return Of Results In Epigenetic Research., Stephanie O M Dyke, Katie M. Saulnier, Charles Dupras, Amy P. Webster, Karen Maschke, Mark Rothstein, Reiner Siebert, Jörn Walter, Stephan Beck, T Pastinen, Yann Joly May 2019

Points-To-Consider On The Return Of Results In Epigenetic Research., Stephanie O M Dyke, Katie M. Saulnier, Charles Dupras, Amy P. Webster, Karen Maschke, Mark Rothstein, Reiner Siebert, Jörn Walter, Stephan Beck, T Pastinen, Yann Joly

Manuscripts, Articles, Book Chapters and Other Papers

As epigenetic studies become more common and lead to new insights into health and disease, the return of individual epigenetic results to research participants, in particular in large-scale epigenomic studies, will be of growing importance. Members of the International Human Epigenome Consortium (IHEC) Bioethics Workgroup considered the potential ethical, legal, and social issues (ELSI) involved in returning epigenetic research results and incidental findings in order to produce a set of 'Points-to-consider' (P-t-C) for the epigenetics research community. These P-t-C draw on existing guidance on the return of genetic research results, while also integrating the IHEC Bioethics Workgroup's ELSI research on …


Comparison Of Methods Used To Estimate The Global Burden Of Disease Related To Undernutrition And Suboptimal Breastfeeding, Alexander C. Mclain, Edward A. Frongillo Jr., Sonja Y. Hess, Ellen G. Piwoz May 2019

Comparison Of Methods Used To Estimate The Global Burden Of Disease Related To Undernutrition And Suboptimal Breastfeeding, Alexander C. Mclain, Edward A. Frongillo Jr., Sonja Y. Hess, Ellen G. Piwoz

Faculty Publications

The Global Burden of Disease study (GBD) is an ambitious effort to estimate the disease burden attributable to various risk factors. The results from the GBD are used around the world to monitor the UN established Sustainable Development Goals, set health policies and research strategies, among others. The GBD along with other studies, such as those from the Maternal Child Epidemiology Estimation Group and the Lancet Breastfeeding Series Group, produce estimates of the nutrition-related global burden of disease that exhibit considerable differences. These differences are difficult to reconcile due to the estimation methods, which in recent years have substantially increased …


How To Conduct Clinical Trials In Children: A Tutorial., Valentina Shakhnovich, Christoph P. Hornik, Gregory L. Kearns, Jaylene Weigel, Susan M. Abdel-Rahman May 2019

How To Conduct Clinical Trials In Children: A Tutorial., Valentina Shakhnovich, Christoph P. Hornik, Gregory L. Kearns, Jaylene Weigel, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

Despite a growing interest in, and commitment to, implementing pediatric clinical trials, approximately one in every five trials in children fails because of inappropriate study design, suboptimal experiment planning, or inadequate participant enrollment. This tutorial, presented from the perspectives of seasoned pediatric investigators, an experienced research coordinator, and an established pediatric clinical trials network, is designed to provide practical guidance for successfully implementing pediatric clinical trials at an academic center or another comparable institution.


Pharmacogene Variation Consortium Gene Introduction: Nudt15., Jun J. Yang, Michelle Whirl-Carrillo, Stuart A. Scott, Amy J. Turner, Matthias Schwab, Yoichi Tanaka, Guilherme Suarez-Kurtz, Elke Schaeffeler, Teri E. Klein, Neil A. Miller, Andrea Gaedigk May 2019

Pharmacogene Variation Consortium Gene Introduction: Nudt15., Jun J. Yang, Michelle Whirl-Carrillo, Stuart A. Scott, Amy J. Turner, Matthias Schwab, Yoichi Tanaka, Guilherme Suarez-Kurtz, Elke Schaeffeler, Teri E. Klein, Neil A. Miller, Andrea Gaedigk

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.


Process Improvement For Follow-Up Radiology Report Recommendations Of Lung Nodules., Philip S. Lim, Doron Schneider, Jonathan Sternlieb, Michel Taupin, Nicholas Sich, Joan Diaz, Eileen Jameson, Bryan Frambes, Sharon Taylor Apr 2019

Process Improvement For Follow-Up Radiology Report Recommendations Of Lung Nodules., Philip S. Lim, Doron Schneider, Jonathan Sternlieb, Michel Taupin, Nicholas Sich, Joan Diaz, Eileen Jameson, Bryan Frambes, Sharon Taylor

Abington Jefferson Health Papers

In the modern healthcare system, there are still wide gaps of communication of imaging results to physician and patient stakeholders and tracking of whether follow-up has occurred. Patients are also unaware of the significance of findings in radiology reports. With the increase in use of cross-sectional imaging such as CT, patients are not only being diagnosed with primary urgent findings but also with incidental findings such as lung nodules; however, they are not being told of their imaging findings nor what actions to take to mitigate their risks. In addition, patients at high risk for developing lung cancer often obtain …


Down Syndrome Mouse Models Have An Abnormal Enteric Nervous System, Ellen M Schill, Christina M Wright, Alisha Jamil, Jonathan M Lacombe, Randall J Roper, Robert O Heuckeroth Apr 2019

Down Syndrome Mouse Models Have An Abnormal Enteric Nervous System, Ellen M Schill, Christina M Wright, Alisha Jamil, Jonathan M Lacombe, Randall J Roper, Robert O Heuckeroth

Open Access Publications

Children with trisomy 21 (Down syndrome [DS]) have a 130-fold increased incidence of Hirschsprung Disease (HSCR), a developmental defect where the enteric nervous system (ENS) is missing from distal bowel (i.e., distal bowel is aganglionic). Treatment for HSCR is surgical resection of aganglionic bowel, but many children have bowel problems after surgery. Post-surgical problems like enterocolitis and soiling are especially common in children with DS. To determine how trisomy 21 affects ENS development, we evaluated the ENS in two DS mouse models, Ts65Dn and Tc1. These mice are trisomic for many chromosome 21 homologous genes, including Dscam and Dyrk1a, which …


The Effect Of Bpifa1/Splunc1 Genetic Variation On Its Expression And Function In Asthmatic Airway Epithelium, Niccolette Schaefer, Mario Castro, Andrea M. Coverstone, Jonathan Boomer, Et Al Apr 2019

The Effect Of Bpifa1/Splunc1 Genetic Variation On Its Expression And Function In Asthmatic Airway Epithelium, Niccolette Schaefer, Mario Castro, Andrea M. Coverstone, Jonathan Boomer, Et Al

Open Access Publications

Bacterial permeability family member A1 (BPIFA1), also known as short palate, lung, and nasal epithelium clone 1 (SPLUNC1), is a protein involved in the antiinflammatory response. The goal of this study was to determine whether BPIFA1 expression in asthmatic airways is regulated by genetic variations, altering epithelial responses to type 2 cytokines (e.g., IL-13). Nasal epithelial cells from patients with mild to severe asthma were collected from the National Heart, Lung, and Blood Institute Severe Asthma Research Program centers, genotyped for rs750064, and measured for BPIFA1. To determine the function of rs750064, cells were cultured at air-liquid interface and treated …


Extracellular Vesicles As Biological Shuttles For Targeted Therapies., Stefania Raimondo, Gianluca Giavaresi, Aurelio Lorico, Riccardo Alessandro Apr 2019

Extracellular Vesicles As Biological Shuttles For Targeted Therapies., Stefania Raimondo, Gianluca Giavaresi, Aurelio Lorico, Riccardo Alessandro

College of Osteopathic Medicine (TUN) Publications and Research

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)-specialized membrane-bound nanocarriers for intercellular communication-suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, …


Gasdermin Pores Permeabilize Mitochondria To Augment Caspase-3 Activation During Apoptosis And Inflammasome Activation., Corey Rogers, Dan A. Erkes, Alexandria Nardone, Andrew E. Aplin, Teresa Fernandes-Alnemri, Emad S. Alnemri Apr 2019

Gasdermin Pores Permeabilize Mitochondria To Augment Caspase-3 Activation During Apoptosis And Inflammasome Activation., Corey Rogers, Dan A. Erkes, Alexandria Nardone, Andrew E. Aplin, Teresa Fernandes-Alnemri, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells. GSDME deficiency also accelerates cell growth in culture and in a mouse model of melanoma. Phosphomimetic mutation of the highly conserved phosphorylatable Thr6 residue of GSDME, inhibits its pore-forming activity, thus uncovering a potential mechanism by which GSDME …


Whatsapp: A Real-Time Tool To Reduce The Knowledge Gap And Share The Best Clinical Practices In Psoriasis, Luis D Mazzuoccolo, Maria Noel Esposito, Paula C Luna, Sharon Seiref, Mirtha Dominguez, Cristina M Echeverria Apr 2019

Whatsapp: A Real-Time Tool To Reduce The Knowledge Gap And Share The Best Clinical Practices In Psoriasis, Luis D Mazzuoccolo, Maria Noel Esposito, Paula C Luna, Sharon Seiref, Mirtha Dominguez, Cristina M Echeverria

Project ECHO Bibliography

BACKGROUND: Psoriasis is a chronic inflammatory disease that affects around 100 million people worldwide. The burden of disease is high, but more recent therapies show promising results. Clinicians need, however, more training in the use of such therapies.

INTRODUCTION: Project ECHO

MATERIALS AND METHODS: One hundred thirty-two dermatologists in Argentina were invited to participate in the WhatsApp discussion group. After 1 year of participation, a follow-up questionnaire was used to assess the effectiveness of the project.

RESULTS: Eighty dermatologists participated. All questions placed in the discussion were answered by a psoriasis specialist, 79% of which were answered within the first …


Rationale And Methods For A Multicenter Clinical Trial Assessing Exercise And Intensive Vascular Risk Reduction In Preventing Dementia (Rrad Study), Amanda N. Szabo-Reed, Eric Vidoni, Ellen F. Binder, Jeffrey Burns, C. Munro Cullum, William P. Gahan, Aditi Gupta, Linda S. Hynan, Diana R. Kerwin, Heidi Rossetti, Ann M. Stowe, Wanpen Vongpatanasin, David C. Zhu, Rong Zhang, Jeffrey N. Keller Apr 2019

Rationale And Methods For A Multicenter Clinical Trial Assessing Exercise And Intensive Vascular Risk Reduction In Preventing Dementia (Rrad Study), Amanda N. Szabo-Reed, Eric Vidoni, Ellen F. Binder, Jeffrey Burns, C. Munro Cullum, William P. Gahan, Aditi Gupta, Linda S. Hynan, Diana R. Kerwin, Heidi Rossetti, Ann M. Stowe, Wanpen Vongpatanasin, David C. Zhu, Rong Zhang, Jeffrey N. Keller

Neurology Faculty Publications

Alzheimer's Disease (AD) is an age-related disease with modifiable risk factors such as hypertension, hypercholesterolemia, obesity, and physical inactivity influencing the onset and progression. There is however, no direct evidence that reducing these risk factors prevents or slows AD. The Risk Reduction for Alzheimer's Disease (rrAD) trial is designed to study the independent and combined effects of intensive pharmacological control of blood pressure and cholesterol and exercise training on neurocognitive function. Six hundred and forty cognitively normal older adults age 60 to 85 years with hypertension and increased risk for dementia will be enrolled. Participants are randomized into one of …


Do Psychopathic Birds Of A Feather Flock Together? Psychopathic Personality Traits And Romantic Preferences, Ashley L Watts, Jessica C Rohr, Katherine L Mccauley, Sarah Francis Smith, Kristin Landfield Howe, Scott O Lilienfeld Apr 2019

Do Psychopathic Birds Of A Feather Flock Together? Psychopathic Personality Traits And Romantic Preferences, Ashley L Watts, Jessica C Rohr, Katherine L Mccauley, Sarah Francis Smith, Kristin Landfield Howe, Scott O Lilienfeld

Staff and Researcher Publications

Objective: The goal of the present studies was to investigate whether people are especially attracted to psychopathic traits, and whether there are individual differences in such attraction.

Method: Female undergraduates (N = 270; Mage = 19; 57% White, 20% Asian, 8% Black) and female and male community members (N = 426; Mage = 37; 56% female; 81% Caucasian, 10% African American, 4% Asian) reported on their own personality and constructed their ideal mate for a dating, short-term, and long-term relationship from a list of 70 characteristics drawn from well-validated criteria for psychopathic personality and diagnostic criteria for DSM-5 personality disorders …


Alterations In Phosphorylation Of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection., Elizabeth K K Glennon, Laura S Austin, Nadia Arang, Heather S Kain, Fred D Mast, Kamalakannan Vijayan, John D Aitchison, Stefan H I Kappe, Alexis Kaushansky Mar 2019

Alterations In Phosphorylation Of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection., Elizabeth K K Glennon, Laura S Austin, Nadia Arang, Heather S Kain, Fred D Mast, Kamalakannan Vijayan, John D Aitchison, Stefan H I Kappe, Alexis Kaushansky

Articles, Abstracts, and Reports

Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated ribosomal protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast …


H3k27m Induces Defective Chromatin Spread Of Prc2-Mediated Repressive H3k27me2/Me3 And Is Essential For Glioma Tumorigenesis., Ashot S. Harutyunyan, Brian Krug, Haifen Chen, Simon Papillon-Cavanagh, Michele Zeinieh, Nicolas De Jay, Shriya Deshmukh, Carol C L Chen, Jad Belle, Leonie G. Mikael, Dylan M. Marchione, Rui Li, Hamid Nikbakht, Bo Hu, Gael Cagnone, Warren A. Cheung, Abdulshakour Mohammadnia, Denise Bechet, Damien Faury, Melissa K. Mcconechy, Manav Pathania, Siddhant U. Jain, Benjamin Ellezam, Alexander G. Weil, Alexandre Montpetit, Paolo Salomoni, Tomi Pastinen, Chao Lu, Peter W. Lewis, Benjamin A. Garcia, Claudia L. Kleinman, Nada Jabado, Jacek Majewski Mar 2019

H3k27m Induces Defective Chromatin Spread Of Prc2-Mediated Repressive H3k27me2/Me3 And Is Essential For Glioma Tumorigenesis., Ashot S. Harutyunyan, Brian Krug, Haifen Chen, Simon Papillon-Cavanagh, Michele Zeinieh, Nicolas De Jay, Shriya Deshmukh, Carol C L Chen, Jad Belle, Leonie G. Mikael, Dylan M. Marchione, Rui Li, Hamid Nikbakht, Bo Hu, Gael Cagnone, Warren A. Cheung, Abdulshakour Mohammadnia, Denise Bechet, Damien Faury, Melissa K. Mcconechy, Manav Pathania, Siddhant U. Jain, Benjamin Ellezam, Alexander G. Weil, Alexandre Montpetit, Paolo Salomoni, Tomi Pastinen, Chao Lu, Peter W. Lewis, Benjamin A. Garcia, Claudia L. Kleinman, Nada Jabado, Jacek Majewski

Manuscripts, Articles, Book Chapters and Other Papers

Lys-27-Met mutations in histone 3 genes (H3K27M) characterize a subgroup of deadly gliomas and decrease genome-wide H3K27 trimethylation. Here we use primary H3K27M tumor lines and isogenic CRISPR-edited controls to assess H3K27M effects in vitro and in vivo. We find that whereas H3K27me3 and H3K27me2 are normally deposited by PRC2 across broad regions, their deposition is severely reduced in H3.3K27M cells. H3K27me3 is unable to spread from large unmethylated CpG islands, while H3K27me2 can be deposited outside these PRC2 high-affinity sites but to levels corresponding to H3K27me3 deposition in wild-type cells. Our findings indicate that PRC2 recruitment and propagation on …


Development And Validation Of The Policies, Opportunities, Initiatives And Notable Topics (Points) Audit For Campuses And Worksites., Tanya M Horacek, Marlei Simon, Elif Dede Yildirim, Adrienne A White, Karla P Shelnutt, Kristin Riggsbee, Melissa D. Olfert, Jesse Stabile Morrell, Anne E Mathews, Wenjun Zhou, Tandalayo Kidd, Kendra Kattelmann, Geoffrey Greene, Lisa Franzen-Castle, Sarah Colby, Carol Byrd-Bredbenner, Onikia Brown Mar 2019

Development And Validation Of The Policies, Opportunities, Initiatives And Notable Topics (Points) Audit For Campuses And Worksites., Tanya M Horacek, Marlei Simon, Elif Dede Yildirim, Adrienne A White, Karla P Shelnutt, Kristin Riggsbee, Melissa D. Olfert, Jesse Stabile Morrell, Anne E Mathews, Wenjun Zhou, Tandalayo Kidd, Kendra Kattelmann, Geoffrey Greene, Lisa Franzen-Castle, Sarah Colby, Carol Byrd-Bredbenner, Onikia Brown

Health and Nutritional Sciences Faculty Publications

Background: Workplace or campus wellness/obesity-prevention policies and initiatives can improve health. Research tools to assess worksite or campus policies/initiatives are scarce. Thus, the aim of this research is to develop and validate the policies, opportunities, initiatives, and notable topics (POINTS) audit. Methods: POINTS was developed and refined via expert review, pilot-testing, and field testing. Trained researchers completed a web-based review from a student-focus or employee-focus regarding 34 health-promoting topics for colleges. Each topic was evaluated on a 0⁻2 scale: 0 = no policy/initiative, 1 = initiatives, 2 = written policy. When a written policy was detected, additional policy support questions …


Comparison Of A Prototype For Indications-Based Prescribing With 2 Commercial Prescribing Systems, Pamela M. Garabedian, Joanna Abraham, Et Al Mar 2019

Comparison Of A Prototype For Indications-Based Prescribing With 2 Commercial Prescribing Systems, Pamela M. Garabedian, Joanna Abraham, Et Al

Open Access Publications

Importance: The indication (reason for use) for a medication is rarely included on prescriptions despite repeated recommendations to do so. One barrier has been the way existing electronic prescribing systems have been designed.

Objective: To evaluate, in comparison with the prescribing modules of 2 leading electronic health record prescribing systems, the efficiency, error rate, and satisfaction with a new computerized provider order entry prototype for the outpatient setting that allows clinicians to initiate prescribing using the indication.

Design, Setting, and Participants: This quality improvement study used usability tests requiring internal medicine physicians, residents, and physician assistants to enter prescriptions electronically, …


Neoantigen Screening Identifies Broad Tp53 Mutant Immunogenicity In Patients With Epithelial Cancers., Parisa Malekzadeh, Anna Pasetto, Paul F Robbins, Maria R Parkhurst, Biman C Paria, Li Jia, Jared J Gartner, Victoria Hill, Zhiya Yu, Nicholas P Restifo, Abraham Sachs, Eric Tran, Winifred Lo, Robert Pt Somerville, Steven A Rosenberg, Drew C Deniger Mar 2019

Neoantigen Screening Identifies Broad Tp53 Mutant Immunogenicity In Patients With Epithelial Cancers., Parisa Malekzadeh, Anna Pasetto, Paul F Robbins, Maria R Parkhurst, Biman C Paria, Li Jia, Jared J Gartner, Victoria Hill, Zhiya Yu, Nicholas P Restifo, Abraham Sachs, Eric Tran, Winifred Lo, Robert Pt Somerville, Steven A Rosenberg, Drew C Deniger

Articles, Abstracts, and Reports

No abstract provided.


A Pilot Study Identifying Brain-Targeting Adaptive Immunity In Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury, Sterling B. Ortega, Poornima Pandiyan, Jana Windsor, Vanessa O. Torres, Uma M. Selvaraj, Amy Lee, Michael Morriss, Fenghua Tian, Lakshmi Raman, Ann M. Stowe Mar 2019

A Pilot Study Identifying Brain-Targeting Adaptive Immunity In Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury, Sterling B. Ortega, Poornima Pandiyan, Jana Windsor, Vanessa O. Torres, Uma M. Selvaraj, Amy Lee, Michael Morriss, Fenghua Tian, Lakshmi Raman, Ann M. Stowe

Neurology Faculty Publications

OBJECTIVES: Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury.

DESIGN: A single center prospective observational study.

SETTING: Pediatric and cardiac ICUs at a single tertiary care, academic center.

PATIENTS: Twenty pediatric extracorporeal membrane oxygenation patients (0-14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Venous blood samples were …


Genetics Of Group A Streptococci, Kyu Hong Cho, Gary C Port, Michael Caparon Mar 2019

Genetics Of Group A Streptococci, Kyu Hong Cho, Gary C Port, Michael Caparon

Open Access Publications

No abstract provided.


Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath Feb 2019

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …


Insulin Resistance And Chronic Kidney Disease Progression, Cardiovascular Events, And Death: Findings From The Chronic Renal Insufficiency Cohort Study, Sarah J Schrauben, Patricia Kao, Et Al Feb 2019

Insulin Resistance And Chronic Kidney Disease Progression, Cardiovascular Events, And Death: Findings From The Chronic Renal Insufficiency Cohort Study, Sarah J Schrauben, Patricia Kao, Et Al

Open Access Publications

BACKGROUND: Insulin resistance contributes to the metabolic syndrome, which is associated with the development of kidney disease. However, it is unclear if insulin resistance independently contributes to an increased risk of chronic kidney disease (CKD) progression or CKD complications. Additionally, predisposing factors responsible for insulin resistance in the absence of diabetes in CKD are not well described. This study aimed to describe factors associated with insulin resistance and characterize the relationship of insulin resistance to CKD progression, cardiovascular events and death among a cohort of non-diabetics with CKD.

METHODS: Data was utilized from Chronic Renal Insufficiency Cohort Study participants without …


A Visual Interactive Analytic Tool For Filtering And Summarizing Large Health Data Sets Coded With Hierarchical Terminologies (Viads)., Xia Jing, Matthew Emerson, David Masters, Matthew Brooks, Jacob Buskirk, Nasseef Abukamail, Chang Liu, James J. Cimino, Jay H. Shubrook, Sonsoles De Lacalle, Yuchun Zhou, Vimla L. Patel Feb 2019

A Visual Interactive Analytic Tool For Filtering And Summarizing Large Health Data Sets Coded With Hierarchical Terminologies (Viads)., Xia Jing, Matthew Emerson, David Masters, Matthew Brooks, Jacob Buskirk, Nasseef Abukamail, Chang Liu, James J. Cimino, Jay H. Shubrook, Sonsoles De Lacalle, Yuchun Zhou, Vimla L. Patel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

BACKGROUND: Vast volumes of data, coded through hierarchical terminologies (e.g., International Classification of Diseases, Tenth Revision-Clinical Modification [ICD10-CM], Medical Subject Headings [MeSH]), are generated routinely in electronic health record systems and medical literature databases. Although graphic representations can help to augment human understanding of such data sets, a graph with hundreds or thousands of nodes challenges human comprehension. To improve comprehension, new tools are needed to extract the overviews of such data sets. We aim to develop a visual interactive analytic tool for filtering and summarizing large health data sets coded with hierarchical terminologies (VIADS) as an online, and publicly …


Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye Feb 2019

Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, …


Gene Therapy Targeting Sarm1 Blocks Pathological Axon Degeneration In Mice, Stefanie Geisler, Shay X. Huang, Amy Strickland, Ryan A. Doan, Daniel W. Summers, Xianrong Mao, Jiwoong Park, Aaron Diantonio, Jeffrey Milbrandt Feb 2019

Gene Therapy Targeting Sarm1 Blocks Pathological Axon Degeneration In Mice, Stefanie Geisler, Shay X. Huang, Amy Strickland, Ryan A. Doan, Daniel W. Summers, Xianrong Mao, Jiwoong Park, Aaron Diantonio, Jeffrey Milbrandt

Open Access Publications

Axonal degeneration (AxD) following nerve injury, chemotherapy, and in several neurological disorders is an active process driven by SARM1, an injury-activated NADase. Axons of SARM1-null mice exhibit greatly delayed AxD after transection and in models of neurological disease, suggesting that inhibiting SARM1 is a promising strategy to reduce pathological AxD. Unfortunately, no drugs exist to target SARM1. We, therefore, developed SARM1 dominant-negatives that potently block AxD in cellular models of axotomy and neuropathy. To assess efficacy in vivo, we used adeno-associated virus-mediated expression of the most potent SARM1 dominant-negative and nerve transection as a model of severe AxD. While axons …


Gen-1 Immunotherapy For The Treatment Of Ovarian Cancer, Premal H Thaker, Nicholas Borys, Jason Fewell, Khursheed Anwer Feb 2019

Gen-1 Immunotherapy For The Treatment Of Ovarian Cancer, Premal H Thaker, Nicholas Borys, Jason Fewell, Khursheed Anwer

2010-2019 OA Pubs

GEN-1 is a gene-based immunotherapy, comprising a human IL-12 gene expression plasmid and a synthetic plasmid delivery system, delivered intraperitoneally (ip.) to produce local and persistent levels of a pleiotropic immunocytokine, IL-12, at the tumor site in patients with advanced ovarian cancer. The goal of local and persistent IL-12 delivery is to remodel the highly immunosuppressive tumor microenvironment to favor immune stimulation while avoiding serious systemic toxicities, a major limitation of recombinant IL-12 therapy. Safe and sustained local production of IL-12 and related immunocytokines at the tumor site could produce potentially more favorable immunological changes in the tumor microenvironment and …


The History And Future Of Digital Health In The Field Of Behavioral Medicine., Danielle Arigo, Danielle E Jake-Schoffman, Kathleen Wolin, Ellen Beckjord, Eric B Hekler, Sherry L Pagoto Feb 2019

The History And Future Of Digital Health In The Field Of Behavioral Medicine., Danielle Arigo, Danielle E Jake-Schoffman, Kathleen Wolin, Ellen Beckjord, Eric B Hekler, Sherry L Pagoto

College of Science & Mathematics Departmental Research

Since its earliest days, the field of behavioral medicine has leveraged technology to increase the reach and effectiveness of its interventions. Here, we highlight key areas of opportunity and recommend next steps to further advance intervention development, evaluation, and commercialization with a focus on three technologies: mobile applications (apps), social media, and wearable devices. Ultimately, we argue that future of digital health behavioral science research lies in finding ways to advance more robust academic-industry partnerships. These include academics consciously working towards preparing and training the work force of the twenty first century for digital health, actively working towards advancing methods …


Penetrating Atherosclerotic Ulcer Of The Ascending Aorta Found Incidentally In A 71-Year-Old Man, Antonino M Grande, Dario Di Perna, Adele Valentini, Eloisa Arbustini Feb 2019

Penetrating Atherosclerotic Ulcer Of The Ascending Aorta Found Incidentally In A 71-Year-Old Man, Antonino M Grande, Dario Di Perna, Adele Valentini, Eloisa Arbustini

The Texas Heart Institute Journal

No abstract provided.


Cardiac Replacement In Our Lifetime, Jack G Copeland Feb 2019

Cardiac Replacement In Our Lifetime, Jack G Copeland

The Texas Heart Institute Journal

No abstract provided.