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Airway Secretory Micrornaome Changes During Rhinovirus Infection In Early Childhood., M. Gutierrez, J. Gomez, Geovanny Perez, Krishna Pancham, Dinesh K. Pillai, M. Giri, S. Ferrante, Robert J. Freishtat, Mary C. Rose, Diego A. Preciado, Gustavo Nino Sep 2016

Airway Secretory Micrornaome Changes During Rhinovirus Infection In Early Childhood., M. Gutierrez, J. Gomez, Geovanny Perez, Krishna Pancham, Dinesh K. Pillai, M. Giri, S. Ferrante, Robert J. Freishtat, Mary C. Rose, Diego A. Preciado, Gustavo Nino

Pediatrics Faculty Publications

BACKGROUND:

Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood.

METHODS:

Nasal airway secretions were obtained from …


Identification Of Pathway-Specific Serum Biomarkers Of Response To Glucocorticoid And Infliximab Treatment In Children With Inflammatory Bowel Disease, Christopher R. Heier, Alyson A. Fiorillo, Ellen Chaisson, Heather A. Gordish-Dressman, Yetrib Hathout, Jesse M. Damsker, Eric P. Hoffman, Laurie S. Conklin Sep 2016

Identification Of Pathway-Specific Serum Biomarkers Of Response To Glucocorticoid And Infliximab Treatment In Children With Inflammatory Bowel Disease, Christopher R. Heier, Alyson A. Fiorillo, Ellen Chaisson, Heather A. Gordish-Dressman, Yetrib Hathout, Jesse M. Damsker, Eric P. Hoffman, Laurie S. Conklin

Genomics and Precision Medicine Faculty Publications

Objective:

Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial.

Methods:

We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7). Over 1,100 serum proteins were assayed using aptamer-based SOMAscan proteomics, and 22 miRNAs analyzed …


Irisin Lowers Blood Pressure By Improvement Of Endothelial Dysfunction Via Ampk‐Akt‐Enos‐No Pathway In The Spontaneously Hypertensive Rat, Jinjuan Fu, Yu Han, Jialiang Wang, Yukai Liu, Shuo Zeng, Lin Zhou, Pedro A. Jose, Chunyu Zeng Sep 2016

Irisin Lowers Blood Pressure By Improvement Of Endothelial Dysfunction Via Ampk‐Akt‐Enos‐No Pathway In The Spontaneously Hypertensive Rat, Jinjuan Fu, Yu Han, Jialiang Wang, Yukai Liu, Shuo Zeng, Lin Zhou, Pedro A. Jose, Chunyu Zeng

Medicine Faculty Publications

Background Exercise is a major nonpharmacological treatment for hypertension, but its underlying mechanisms are still not completely elucidated. Irisin, a polypeptide containing 112 amino acids, which is secreted mainly by skeletal muscle cells during exercise, exerts a protective role in metabolic diseases, such as diabetes mellitus and obesity. Because of the close relationship between irisin and metabolic diseases, we hypothesized that irisin may play a role in the regulation of blood pressure.

Methods and Results Blood pressures of male Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were monitored through the carotid artery. Our study found that acute intravenous injection …


The Rise And Rise Of Neurosurgery: Academic Journey Of A Young Department In A Developing Country, Muhammad Shahzad Shamim, Hamid Hussain Rai Hussain Rai Sep 2016

The Rise And Rise Of Neurosurgery: Academic Journey Of A Young Department In A Developing Country, Muhammad Shahzad Shamim, Hamid Hussain Rai Hussain Rai

Pakistan Journal of Neurological Sciences (PJNS)

The Section of Neurosurgery, part of the Department of Surgery, and the Mind and Brain Service Line at the Aga Khan University Hospital Karachi, has come a long way since its recognition in mid-90s. Although the program itself was recognized in late 90’s and the first resident graduated in 2004, it wasn't until 2008 that it assumed its current shape of a formal, structured training program. Currently it has six full-time faculty members, one part-time faculty member, two instructors, and a team of 12 residents. Following are few of the innovations introduced within the program over the last few years.


Oncolog, Volume 61, Number 09, September 2016, Jill Delsigne-Russell, Brandon C. Strubberg, E Nielsen Sep 2016

Oncolog, Volume 61, Number 09, September 2016, Jill Delsigne-Russell, Brandon C. Strubberg, E Nielsen

OncoLog MD Anderson's Report to Physicians (All issues) Archives

  • Transport Oncophysics Could Guide Pancreatic Cancer Treatment: Pancreatic ductal adenocarcinomas respond poorly to standard treatments. Researchers at The University of Texas MD Anderson Cancer Center are applying the principles of physics to characterize the tumors, and these analyses could lead to individualized therapy.
  • Nivolumab Shows Potential in Treating Squamous Cell Carcinoma of the Anal Canal: Currently, there are no standard therapy options for patients with treatment-refractory metastatic squamous cell carcinoma of the anal canal (SCCA), but early results of a multi-institutional clinical trial (No. NCI9673) led by researchers at The University of Texas MD Anderson Cancer Center show that the …


Neurogenic Fever After Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review., Katherine E. Savage, Christina V. Oleson, Gregory D. Schroeder, Gursukhman S Sidhu, Alex R. Vaccaro Sep 2016

Neurogenic Fever After Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review., Katherine E. Savage, Christina V. Oleson, Gregory D. Schroeder, Gursukhman S Sidhu, Alex R. Vaccaro

Rothman Institute Papers

STUDY DESIGN: Systematic review.

OBJECTIVE: To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI).

METHODS: A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained.

RESULTS: The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. …


Association Of Tobacco Use And Other Determinants With Pregnancy Outcomes: A Multicentre Hospital-Based Case-Control Study In Karachi, Pakistan., Shafquat Rozi, Zahid Ahmad Butt, Nida Zahid, Saba Wasim, Kashif Shafique Sep 2016

Association Of Tobacco Use And Other Determinants With Pregnancy Outcomes: A Multicentre Hospital-Based Case-Control Study In Karachi, Pakistan., Shafquat Rozi, Zahid Ahmad Butt, Nida Zahid, Saba Wasim, Kashif Shafique

Community Health Sciences

OBJECTIVES:

The study aimed to identify the effects of maternal tobacco consumption during pregnancy and other factors on birth outcomes and obstetric complications in Karachi, Pakistan.

DESIGN:

A multicentre hospital-based case-control study.

SETTING:

Four leading maternity hospitals of Karachi.

PARTICIPANTS:

A random sample of 1275 women coming to the gynaecology and obstetric department of selected hospitals for delivery was interviewed within 48 hours of delivery from wards. Cases were women with adverse birth outcomes and obstetric complications, while controls were women who had normal uncomplicated delivery.

PRIMARY AND SECONDARY OUTCOME MEASURES:

Adverse birth outcomes (preterm delivery, low birth weight, stillbirth, …


Geographic And Age-Based Variations In Medicare Reimbursement Among Assh Members., Michael P. Gaspar, Patrick M. Kane, Grace B. Honik, Eon K. Shin, Sidney M. Jacoby, A. Lee Osterman Sep 2016

Geographic And Age-Based Variations In Medicare Reimbursement Among Assh Members., Michael P. Gaspar, Patrick M. Kane, Grace B. Honik, Eon K. Shin, Sidney M. Jacoby, A. Lee Osterman

Department of Orthopaedic Surgery Faculty Papers

Background: The purpose of this study was to investigate how American Society for Surgery of the Hand (ASSH) members' Medicare reimbursement depends on their geographical location and number of years in practice. Methods: Demographic data for surgeons who were active members of the ASSH in 2012 were obtained using information publicly available through the US Centers for Medicare and Medicaid Services (CMS). "Hand-surgeons-per-capita" and average reimbursement per surgeon were calculated for each state. Regression analysis was performed to determine a relationship between (1) each state's average reimbursement versus the number of ASSH members in that state, (2) average reimbursement versus …


Chemical Modification Of Extracellular Matrix By Cold Atmospheric Plasma-Generated Reactive Species Affects Chondrogenesis And Bone Formation., Peter Eisenhauer, Natalie Chernets, You Song, Danil Dobrynin, Nancy Pleshko, Marla J Steinbeck, Theresa A. Freeman Sep 2016

Chemical Modification Of Extracellular Matrix By Cold Atmospheric Plasma-Generated Reactive Species Affects Chondrogenesis And Bone Formation., Peter Eisenhauer, Natalie Chernets, You Song, Danil Dobrynin, Nancy Pleshko, Marla J Steinbeck, Theresa A. Freeman

Department of Orthopaedic Surgery Faculty Papers

The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or …


Progestogen-Only Contraceptive Use Among Breastfeeding Women: A Systematic Review., Sharon J. Phillips, Naomi K. Tepper, Nathalie Kapp, Kavita Nanda, Marleen Temmerman, Kathryn M. Curtis Sep 2016

Progestogen-Only Contraceptive Use Among Breastfeeding Women: A Systematic Review., Sharon J. Phillips, Naomi K. Tepper, Nathalie Kapp, Kavita Nanda, Marleen Temmerman, Kathryn M. Curtis

Obstetrics and Gynaecology, East Africa

Background: Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and infant health outcomes.

Objectives: We investigated the clinical outcomes of breastfeeding duration, initiation of supplemental feeding and weaning, as well as infant outcomes including infant growth, health and development among breastfeeding women using POCs compared with breastfeeding women not using POCs.

Search strategy: We searched the PubMed database for all articles published from database inception through December 2014.

Selection criteria: We included primary research studies of breastfeeding women of any age or parity who received POCs, including progestogen-only pills, …


Stimulation Of Transforming Growth Factor-Β1-Induced Endothelial-To-Mesenchymal Transition And Tissue Fibrosis By Endothelin-1 (Et-1): A Novel Profibrotic Effect Of Et-1., Peter J. Wermuth, Zhaodong Li, Fabian A. Mendoza, Sergio A. Jimenez Sep 2016

Stimulation Of Transforming Growth Factor-Β1-Induced Endothelial-To-Mesenchymal Transition And Tissue Fibrosis By Endothelin-1 (Et-1): A Novel Profibrotic Effect Of Et-1., Peter J. Wermuth, Zhaodong Li, Fabian A. Mendoza, Sergio A. Jimenez

Department of Medicine Faculty Papers

TGF-β-induced endothelial-to-mesenchymal transition (EndoMT) is a newly recognized source of profibrotic activated myofibroblasts and has been suggested to play a role in the pathogenesis of various fibrotic processes. Endothelin-1 (ET-1) has been implicated in the development of tissue fibrosis but its participation in TGF-β-induced EndoMT has not been studied. Here we evaluated the role of ET-1 on TGF-β1-induced EndoMT in immunopurified CD31+/CD102+ murine lung microvascular endothelial cells. The expression levels of α-smooth muscle actin (α-SMA), of relevant profibrotic genes, and of various transcription factors involved in the EndoMT process were assessed employing quantitative RT-PCR, immunofluorescence histology and Western blot analysis. …


Microdose Fluorescence Imaging Of Aby-029 On An Operating Microscope Adapted By Custom Illumination And Imaging Modules, Jonathan T. Elliott, Alisha V. Dsouza, Kayla Marra, Brian W. Pogue, David Roberts, Keith Paulsen Sep 2016

Microdose Fluorescence Imaging Of Aby-029 On An Operating Microscope Adapted By Custom Illumination And Imaging Modules, Jonathan T. Elliott, Alisha V. Dsouza, Kayla Marra, Brian W. Pogue, David Roberts, Keith Paulsen

Dartmouth Scholarship

Fluorescence guided surgery has the potential to positively impact surgical oncology; current operating microscopes and stand-alone imaging systems are too insensitive or too cumbersome to maximally take advantage of new tumor-specific agents developed through the microdose pathway. To this end, a custom-built illumination and imaging module enabling picomolar-sensitive near-infrared fluorescence imaging on a commercial operating microscope is described. The limits of detection and system specifications are characterized, and in vivo efficacy of the system in detecting ABY-029 is evaluated in a rat orthotopic glioma model following microdose injections, showing the suitability of the device for microdose phase 0 clinical trials.


Nutrition In Intensive Care In Adults Review Of The Literature And Development Of Evidence Based Feeding Protocols., Sarah Ikram, Erfan Hussain,, Ali Bin Sarwar Zubairi Sep 2016

Nutrition In Intensive Care In Adults Review Of The Literature And Development Of Evidence Based Feeding Protocols., Sarah Ikram, Erfan Hussain,, Ali Bin Sarwar Zubairi

Department of Medicine

The subject of nutrition in intensive care is broad.Thenutrition support therapy plays a crucial role in the management of critically ill patients. This review was carried out to address the existing controversies and to recognise the current practice guidelines for the management of nutrition in intensive care units (ICUs) in adults. A PubMed search was carried out for clinical trials addressing the current nutrition practice in ICUs, recommendations for calculating energy requirements and efficacy of an algorithmic approach to nutritional delivery in an ICU setting. Algorithms were developed and modified for the practice of nutrition in an adult ICU in …


Multi-Focal Control Of Mitochondrial Gene Expression By Oncogenic Myc Provides Potential Therapeutic Targets In Cancer., Amanda R. Oran, Clare M. Adams, Xiao-Yong Zhang, Victoria J. Gennaro, Harla K. Pfeiffer, Hestia S. Mellert, Hans E. Seidel, Kirsten Mascioli, Jordan Kaplan, Mahmoud R. Gaballa, Chen Shen, Isidore Rigoutsos, Michael P. King, Justin L Cotney, Jamie J. Arnold, Suresh D. Sharma, Ubaldo E. Martinez-Outshoorn, Christopher R. Vakoc, Lewis A. Chodosh, James E. Thompson, James E. Bradner, Craig E. Cameron, Gerald S. Shadel, Christine M. Eischen, Steven B. Mcmahon Aug 2016

Multi-Focal Control Of Mitochondrial Gene Expression By Oncogenic Myc Provides Potential Therapeutic Targets In Cancer., Amanda R. Oran, Clare M. Adams, Xiao-Yong Zhang, Victoria J. Gennaro, Harla K. Pfeiffer, Hestia S. Mellert, Hans E. Seidel, Kirsten Mascioli, Jordan Kaplan, Mahmoud R. Gaballa, Chen Shen, Isidore Rigoutsos, Michael P. King, Justin L Cotney, Jamie J. Arnold, Suresh D. Sharma, Ubaldo E. Martinez-Outshoorn, Christopher R. Vakoc, Lewis A. Chodosh, James E. Thompson, James E. Bradner, Craig E. Cameron, Gerald S. Shadel, Christine M. Eischen, Steven B. Mcmahon

Department of Cancer Biology Faculty Papers

Despite ubiquitous activation in human cancer, essential downstream effector pathways of the MYC transcription factor have been difficult to define and target. Using a structure/function-based approach, we identified the mitochondrial RNA polymerase (POLRMT) locus as a critical downstream target of MYC. The multifunctional POLRMT enzyme controls mitochondrial gene expression, a process required both for mitochondrial function and mitochondrial biogenesis. We further demonstrate that inhibition of this newly defined MYC effector pathway causes robust and selective tumor cell apoptosis, via an acute, checkpoint-like mechanism linked to aberrant electron transport chain complex assembly and mitochondrial reactive oxygen species (ROS) production. Fortuitously, MYC-dependent …


Benefits Of A Flexitarian Diet: Educating College Students Of Lifestyle Approaches To Reduce The Risk Of Developing Breast And Prostate Cancer, Abbigail Pace Aug 2016

Benefits Of A Flexitarian Diet: Educating College Students Of Lifestyle Approaches To Reduce The Risk Of Developing Breast And Prostate Cancer, Abbigail Pace

Mahurin Honors College Capstone Experience/Thesis Projects

Practicing the Flexitarian diet, a plant-based diet, in conjunction with physical activity can promote a lifestyle consistent with the American Cancer Society’s recommendations for reducing risks of breast and prostate cancer (American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention, 2015) College students were assessed on knowledge of the relationship between diet and cancer risk prior to and after accessing information on the American Institute of Cancer Research site or the WKU Flexitarian Pinterest Page. Participants were recruited from the National Panhellenic and Interfraternity Council memberships and the International students at Western Kentucky University. Participants completed a …


Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemoradiation Therapy Outcomes, Lixin Dong, Mahesh Kudrimoti, Daniel Irwin, Li Chen, Sameera Kumar, Yu Shang, Chong Huang, Ellis L. Johnson, Scott D. Stevens, Brent J. Shelton, Guoqiang Yu Aug 2016

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemoradiation Therapy Outcomes, Lixin Dong, Mahesh Kudrimoti, Daniel Irwin, Li Chen, Sameera Kumar, Yu Shang, Chong Huang, Ellis L. Johnson, Scott D. Stevens, Brent J. Shelton, Guoqiang Yu

Biomedical Engineering Faculty Publications

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n = 29) and incomplete response (IR) (n = 18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 …


Nox2-Derived Oxidative Stress Results In Inefficacy Of Antibiotics Against Post-Influenza S. Aureus Pneumonia., Keer Sun, Vijaya Kumar Yajjala, Christopher Bauer, G. Talmon, Karl J. Fischer, Tammy Kielian, Dennis W. Metzger Aug 2016

Nox2-Derived Oxidative Stress Results In Inefficacy Of Antibiotics Against Post-Influenza S. Aureus Pneumonia., Keer Sun, Vijaya Kumar Yajjala, Christopher Bauer, G. Talmon, Karl J. Fischer, Tammy Kielian, Dennis W. Metzger

Journal Articles: Pathology and Microbiology

Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)-deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress-associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress increased …


Regulation Of Nachrs And Stemness By Nicotine And E-Cigarettes In Nsclc, Courtney Schaal Aug 2016

Regulation Of Nachrs And Stemness By Nicotine And E-Cigarettes In Nsclc, Courtney Schaal

USF Tampa Graduate Theses and Dissertations

Lung cancer is the leading cause of cancer-related death in both men and women, nationally and internationally and kills more people each year than breast, prostate, and colon cancers combined. Non-small cell lung carcinoma (NSCLC) is the most common histological subtype of lung cancer, and accounts for 85% of all cases. Cigarette smoking is the single greatest risk factor for lung cancer, and is correlated with 80-90% of all lung cancer deaths. Nicotine, the addictive component of tobacco smoke, is not a carcinogen and cannot initiate tumors itself; however, it is known to act as a tumor promoter, by enhancing …


Changes To Echocardiography-Derived Left Ventricular Filling Pressures And Cardiac Output In Response To Fluid Boluses In Elderly Patients With Left Ventricular Diastolic Dysfunction Undergoing Vascular Surgery, Sasha K. Shillcutt Aug 2016

Changes To Echocardiography-Derived Left Ventricular Filling Pressures And Cardiac Output In Response To Fluid Boluses In Elderly Patients With Left Ventricular Diastolic Dysfunction Undergoing Vascular Surgery, Sasha K. Shillcutt

Theses & Dissertations

Left ventricular diastolic dysfunction (LVDD) of the heart is a condition where the heart does not relax properly. This condition is important during times of stress, as LVDD is associated with significant morbidity of elderly surgical patients. LVDD is often asymptomatic and unrecognized as many of these patients have normal ejection fractions. However, LVDD may lead to heart failure in patients with preserved systolic function, with the incidence being as high as 50% in hospitalized elderly patients. The diagnosis of LVDD is an independent risk factor for postoperative major adverse cardiac events (MACE) and negatively impacts post-surgery readmission rates. Anesthesiologists …


Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang Aug 2016

Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of generally aggressive lymphoid malignancies, accounting for 10-15% of all non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) represents approximately 20% of all PTCLs and is recognized as a distinct entity. Accurate diagnosis and classification of PTCL remain challenging. With the exception of ALK+ ALCL, patients with PTCL generally have a poor prognosis with standard chemotherapy and even with the availability of many novel drugs, including HDAC inhibitor (romidepsin and belinostat), gemcitabine, and bortezomib. Therefore, deciphering the pathogenesis of this group of diseases is needed to identify novel treatable targets for better therapeutic intervention. …


The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu Aug 2016

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …


A Hypothesis For Using Pathway Genetic Load Analysis For Understanding Complex Outcomes In Bilirubin Encephalopathy, Sean M. Riordan, Douglas C. Bittel, Jean-Baptist Lepichon, Silvia Gazzin, Claudio Tiribelli, Jon F. Watchko, Richard P. Wennberg, Steven Shapiro Aug 2016

A Hypothesis For Using Pathway Genetic Load Analysis For Understanding Complex Outcomes In Bilirubin Encephalopathy, Sean M. Riordan, Douglas C. Bittel, Jean-Baptist Lepichon, Silvia Gazzin, Claudio Tiribelli, Jon F. Watchko, Richard P. Wennberg, Steven Shapiro

Manuscripts, Articles, Book Chapters and Other Papers

© 2016 Riordan, Bittel, Le Pichon, Gazzin, Tiribelli, Watchko, Wennberg and Shapiro.

Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60-80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. …


Mitochondrial Akt Regulation Of Hypoxic Tumor Reprogramming., Young Chan Chae, Valentina Vaira, M. Cecilia Caino, Hsin-Yao Tang, Jae Ho Seo, Andrew V. Kossenkov, Luisa Ottobrini, Cristina Martelli, Giovanni Lucignani, Irene Bertolini, Marco Locatelli, Kelly G. Bryant, Jagadish C. Ghosh, Sofia Lisanti, Bonsu Ku, Silvano Bosari, Lucia R. Languino, David W. Speicher, Dario C. Altieri Aug 2016

Mitochondrial Akt Regulation Of Hypoxic Tumor Reprogramming., Young Chan Chae, Valentina Vaira, M. Cecilia Caino, Hsin-Yao Tang, Jae Ho Seo, Andrew V. Kossenkov, Luisa Ottobrini, Cristina Martelli, Giovanni Lucignani, Irene Bertolini, Marco Locatelli, Kelly G. Bryant, Jagadish C. Ghosh, Sofia Lisanti, Bonsu Ku, Silvano Bosari, Lucia R. Languino, David W. Speicher, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia. Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers and shorter survival in glioma patients and may provide an "actionable" therapeutic target in cancer.


Binge Ethanol Exposure Causes Endoplasmic Reticulum Stress, Oxidative Stress And Tissue Injury In The Pancreas, Zhenhua Ren, Xin Wang, Mei Xu, Fanmuyi Yang, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo Aug 2016

Binge Ethanol Exposure Causes Endoplasmic Reticulum Stress, Oxidative Stress And Tissue Injury In The Pancreas, Zhenhua Ren, Xin Wang, Mei Xu, Fanmuyi Yang, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Alcohol abuse is associated with both acute and chronic pancreatitis. Repeated episodes of acute pancreatitis or pancreatic injury may result in chronic pancreatitis. We investigated ethanol-induced pancreatic injury using a mouse model of binge ethanol exposure. Male C57BL/6 mice were exposed to ethanol intragastrically (5 g/kg, 25% ethanol w/v) daily for 10 days. Binge ethanol exposure caused pathological changes in pancreas demonstrated by tissue edema, acinar atrophy and moderate fibrosis. Ethanol caused both apoptotic and necrotic cell death which was demonstrated by the increase in active caspase-3, caspase-8, cleaved PARP, cleaved CK-18 and the secretion of high mobility group protein …


Characterization Of Left-Ventricular Thrombus Formation Using High Frequency Ultrasound, Kelsey A. Bullens, Arvin H. Soepriatna, Pavlos P. Vlachos, Craig J. Goergen Aug 2016

Characterization Of Left-Ventricular Thrombus Formation Using High Frequency Ultrasound, Kelsey A. Bullens, Arvin H. Soepriatna, Pavlos P. Vlachos, Craig J. Goergen

The Summer Undergraduate Research Fellowship (SURF) Symposium

Heart failure is a leading cause of death in the United States, and cardiac thrombus, a common morbidity associated with heart failure, significantly increases a patient’s risk of embolic events. The objective of this project is to characterize left-ventricular (LV) thrombus development using high frequency ultrasound imaging in a murine model. C57BL/6J wild-type mice (n=6) were injected intraperitoneally with iron dextran five times a week for six weeks to increase oxidative stress in the heart. Granulocyte-colony stimulating factor (G-CSF) was subcutaneously injected daily during the second week to initiate stem cell migration and stimulate endothelial cell activation, thus increasing the …


The Airway Microbiome At Birth., Charitharth Vivek Lal, Colm Travers, Zubair H. Aghai, Peter Eipers, Tamas Jilling, Brian Halloran, Waldemar A. Carlo, Jordan Keeley, Gabriel Rezonzew, Ranjit Kumar, Casey Morrow, Vineet Bhandari, Namasivayam Ambalavanan Aug 2016

The Airway Microbiome At Birth., Charitharth Vivek Lal, Colm Travers, Zubair H. Aghai, Peter Eipers, Tamas Jilling, Brian Halloran, Waldemar A. Carlo, Jordan Keeley, Gabriel Rezonzew, Ranjit Kumar, Casey Morrow, Vineet Bhandari, Namasivayam Ambalavanan

Department of Pediatrics Faculty Papers

Alterations of pulmonary microbiome have been recognized in multiple respiratory disorders. It is critically important to ascertain if an airway microbiome exists at birth and if so, whether it is associated with subsequent lung disease. We found an established diverse and similar airway microbiome at birth in both preterm and term infants, which was more diverse and different from that of older preterm infants with established chronic lung disease (bronchopulmonary dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were seen from birth to the development of bronchopulmonary dysplasia in extremely preterm infants. Genus Lactobacillus was decreased at birth in …


Avoiding Overtreatment At The End Of Life: Physician-Patient Communication And Truly Informed Consent, Barbara A. Noah, Neal R. Feigenson Aug 2016

Avoiding Overtreatment At The End Of Life: Physician-Patient Communication And Truly Informed Consent, Barbara A. Noah, Neal R. Feigenson

Pace Law Review

This paper’s primary focus will be on considering how best to ensure that patients have the tools to make both informed and authentic choices about their care at the end of life. We will argue that truly informed decision making can help to reduce excessive end-of-life care by any measure. Most importantly for dying patients, better informed decisions can help reduce unnecessary suffering and result in care that aligns with their well-considered values and preferences.

In the first part of this paper, we will explain that, by any of these measures, many dying patients are receiving too much therapy and …


Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, Khm Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman Aug 2016

Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, Khm Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman

Pharmacy Faculty Articles and Research

Avian influenza viruses (AIVs) continue to pose a global threat. Waterfowl are the main reservoir and are responsible for the spillover of AIVs to other hosts. This study was conducted as part of routine surveillance activities in Bangladesh and it reports on the serological and molecular detection of H5N1 AIV subtype. A total of 2169 cloacal and 2191 oropharyngeal swabs as well as 1725 sera samples were collected from live birds including duck and chicken in different locations in Bangladesh between the years of 2013 and 2014. Samples were tested using virus isolation, serological tests and molecular methods of RT-PCR. …


Integrated Molecular Pathway Analysis Informs A Synergistic Combination Therapy Targeting Pten/Pi3k And Egfr Pathways For Basal-Like Breast Cancer, Qing-Bai She, Sofia K. Gruvberger-Saal, Matthew Maurer, Yilun Chen, Mervi Jumppanen, Tao Su, Meaghan Dendy, Ying-Ka Ingar Lau, Lorenzo Memeo, Hugo M. Horlings, Marc J. Van De Vijver, Jorma Isola, Hanina Hibshoosh, Neal Rosen, Ramon Parsons, Lao H. Saal Aug 2016

Integrated Molecular Pathway Analysis Informs A Synergistic Combination Therapy Targeting Pten/Pi3k And Egfr Pathways For Basal-Like Breast Cancer, Qing-Bai She, Sofia K. Gruvberger-Saal, Matthew Maurer, Yilun Chen, Mervi Jumppanen, Tao Su, Meaghan Dendy, Ying-Ka Ingar Lau, Lorenzo Memeo, Hugo M. Horlings, Marc J. Van De Vijver, Jorma Isola, Hanina Hibshoosh, Neal Rosen, Ramon Parsons, Lao H. Saal

Markey Cancer Center Faculty Publications

Background: The basal-like breast cancer (BLBC) subtype is characterized by positive staining for basal mammary epithelial cytokeratin markers, lack of hormone receptor and HER2 expression, and poor prognosis with currently no approved molecularly-targeted therapies. The oncogenic signaling pathways driving basal-like tumorigenesis are not fully elucidated.

Methods: One hundred sixteen unselected breast tumors were subjected to integrated analysis of phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations by immunohistochemistry, mutation analysis, and gene expression profiling. Incidence and relationships between molecular biomarkers were characterized. Findings for select biomarkers were validated in an independent series. Synergistic cell killing in vitro and in vivo tumor …


Inhibition Of Nuclear Factor-Kappa B Enhances The Tumor Growth Of Ovarian Cancer Cell Line Derived From A Low-Grade Papillary Serous Carcinoma In P53-Independent Pathway, Xue Xiao, Gong Yang, Peng Bai, Shunping Gui, Tri M. Bui Nguyen, +8 Additional Authors Aug 2016

Inhibition Of Nuclear Factor-Kappa B Enhances The Tumor Growth Of Ovarian Cancer Cell Line Derived From A Low-Grade Papillary Serous Carcinoma In P53-Independent Pathway, Xue Xiao, Gong Yang, Peng Bai, Shunping Gui, Tri M. Bui Nguyen, +8 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Background: NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer.

Methods: The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells.

Results: Western blot analysis indicated increased …