Digital Commons Network^™

Bevacizumab: A Rare Cause Of Nonischemic Cardiomyopathy., Oreoluwa Oladiran, Salik Nazir

Reading Hospital Internal Medicine Residency

Left ventricular dysfunction is a rare side effect of bevacizumab occurring in 2-4% of cases. We report the case of a 68-year-old woman who presented to the emergency department (ED) with sudden onset of shortness of breath, orthopnea, and paroxysmal nocturnal dyspnea. She was tachypneic and in respiratory distress. Physical examination revealed jugular venous distention, diffuse expiratory wheeze, and bipedal edema. She had been started on bevacizumab for the treatment of hereditary hemorrhagic telangiectasia 1 month prior to presentation. Laboratory tests revealed BNP of 1697 pg/ml with slightly elevated troponin 0.05 ng/ml. Chest X-ray showed interstitial edema with cardiomegaly, and …

Chronically Implanted Intracranial Electrodes: Tissue Reaction And Electrical Changes., Andrew Campbell, Chengyuan Wu

Department of Neurosurgery Faculty Papers

The brain-electrode interface is arguably one of the most important areas of study in neuroscience today. A stronger foundation in this topic will allow us to probe the architecture of the brain in unprecedented functional detail and augment our ability to intervene in disease states. Over many years, significant progress has been made in this field, but some obstacles have remained elusive-notably preventing glial encapsulation and electrode degradation. In this review, we discuss the tissue response to electrode implantation on acute and chronic timescales, the electrical changes that occur in electrode systems over time, and strategies that are being investigated …

The "Lightning Bolt" Sign On Computed Tomography During Percutaneous Renal Mass Cryoablation, Qian Yu, Driss Raissi

Radiology Faculty Publications

Ice‑ball fracture is a rare and often overlooked entity that may lead to intraprocedural hemorrhage after percutaneous cryoablation of renal masses. There is scant literature on ice‑ball fractures associated with percutaneous renal cryoablation. Immediate recognition of the lightning bolt sign during intraprocedural computed tomography can help identify patients who may have developed this complication.

Depression Following A Traumatic Brain Injury: Uncovering Cytokine Dysregulation As A Pathogenic Mechanism, Colleen N. Bodnar, Josh M. Morganti, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

A substantial number of individuals have long-lasting adverse effects from a traumatic brain injury (TBI). Depression is one of these long-term complications that influences many aspects of life. Depression can limit the ability to return to work, and even worsen cognitive function and contribute to dementia. The mechanistic cause for the increased depression risk associated with a TBI remains to be defined. As TBI results in chronic neuroinflammation, and priming of glia to a secondary challenge, the inflammatory theory of depression provides a promising framework for investigating the cause of depression following a TBI. Increases in cytokines similar to those …

Heparin Bridging Therapy Is Not Necessary For Patients With Atrial Fibrillation Undergoing Temporary Interruption Of Warfarin Therapy For Elective Invasive Procedures Or Surgery, Shannon Paquette

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. New Engl J Med. Aug 2015;373(9):823-833. doi: 10.1056/NEJMoa1501035

Sex-Specific Associations Of Infants’ Gut Microbiome With Arsenic Exposure In A Us Population, Anne G. Hoen, Juliette C. Madan, Zhigang Li, Modupe Coker, Sara N. Lundgren, Hilary G. Morrison, Thomas J. Palys, Brian P. Jackson, Mitchell L. Sogin, Kathryn L. Cottingham, Margaret R. Karagas

Dartmouth Scholarship

Arsenic is a ubiquitous environmental toxicant with antimicrobial properties that can be found in food and drinking water. The influence of arsenic exposure on the composition of the human microbiome in US populations remains unknown, particularly during the vulnerable infant period. We investigated the relationship between arsenic exposure and gut microbiome composition in 204 infants prospectively followed as part of the New Hampshire Birth Cohort Study. Infant urine was analyzed for total arsenic concentration using inductively coupled plasma mass spectrometry. Stool microbiome composition was determined using sequencing of the bacterial 16S rRNA gene. Infant urinary arsenic related to gut microbiome …

Considerations For Best Practices In Studies Of Fiber Or Other Dietary Components And The Intestinal Microbiome, David M. Klurfeld, Cindy D. Davis, Robert W. Karp, Emma Allen-Vercoe, Eugene B. Chang, Benoit Chassaing, George C. Fahey Jr, Bruce R. Hamaker, Hannah D. Holscher, Johanna W. Lampe, Andre Marette, Eric Martens, Stephen J. O'Keefe, Devin J. Rose, Maria Saarela, Barbara O. Schneeman, Joanne L. Slavin, Justin L. Sonnenburg, Kelly S. Swanson, Gary D. Wu, Christopher J. Lynch

Food for Health: Publications

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome. Am J Physiol Endocrinol Metab 315: E1087–E1097, 2018. First published August 21, 2018; doi:10.1152/ajpendo.00058.2018.—A 2-day workshop organized by the National Institutes of Health and U.S. Department of Agriculture included 16 presentations focused on the role of diet in alterations of the gastrointestinal microbiome, primarily that of the colon. Although thousands of research projects have been funded by U.S. federal agencies to study the intestinal microbiome of humans and a variety of animal models, only a minority addresses dietary effects, and a small subset is …

Common Pitfalls In Analysis Of Tissue Scores, David K. Meyerholz, Nathan L. Tintle, Amanda P. Beck

Faculty Work Comprehensive List

Histopathology remains an important source of descriptive biological data in biomedical research. Recent petitions for enhanced reproducibility in scientific studies have elevated the role of tissue scoring (semiquantitative and quantitative) in research studies. Effective tissue scoring requires appropriate statistical analysis to help validate the group comparisons and give the pathologist confidence in interpreting the data. Each statistical test is typically founded on underlying assumptions regarding the data. If the underlying assumptions of a statistical test do not match the data, then these tests can lead to increased risk of erroneous interpretations of the data. The choice of appropriate statistical test …

Na/K-Atpase Y260 Phosphorylation-Mediated Src Regulation In Control Of Aerobic Glycolysis And Tumor Growth, Moumita Banerjee, Xiaoyu Cui, Zhichuan Li, Hui Yu, Liquan Cai, Xuelian Jia, Daheng He, Chi Wang, Tianyan Gao, Zijian Xie

Markey Cancer Center Faculty Publications

We report here the identification of α1 Na/K-ATPase as a major regulator of the proto-oncogene Src kinase and the role of this regulation in control of Warburg effect and tumor growth. Specifically, we discovered Y260 in α1 Na/K-ATPase as a Src-specific phosphorylation and binding site and that Y260 phosphorylation is required for Src-mediated signal transduction in response to a number of stimuli including EGF. As such, it enables a dynamic control of aerobic glycolysis. However, such regulation appears to be lost or attenuated in human cancers as the expression of Na/K-ATPase α1 was significantly decreased in prostate, breast and kidney …

Evaluation Of The Diagnostic Accuracy Of Computer-Aided Detection Of Tuberculosis On Chest Radiography Among Private Sector Patients In Pakistan, Syed Mohammad Asad Zaidi, Shifa Salman Habib, Bram Van Ginneke, Rashida Abbas Ferrand, Jacob Creswell, Saira Khowaja, Aamir Khan

Community Health Sciences

The introduction of digital CXR with automated computer-aided interpretation, has given impetus to the role of CXR in TB screening, particularly in low resource, high-burden settings. The aim of this study was to evaluate the diagnostic accuracy of CAD4TB as a screening tool, implemented in the private sector in Karachi, Pakistan. This study analyzed retrospective data from CAD4TB and Xpert MTB/RIF testing carried out at two private TB treatment and diagnostic centers in Karachi. Sensitivity, specificity, potential Xperts saved, were computed and the receiver operator characteristic curves were constructed for four different models of CAD4TB. A total of 6,845 individuals …

Astromimetics: The Dawn Of A New Era For (Bio)Materials Science?, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Composite, multifunctional fine particles are likely to be at the frontier of materials science in the foreseeable future. Here we present a submicron composite particle that mimics the stratified structure of the Earth by having a zero-valent iron core, a silicate/silicide mantle, and a thin carbonaceous crust resembling the biosphere and its biotic deposits. Particles were formulated in a stable colloidal form and made to interact with various types of healthy and cancer cells in vitro. A selective anticancer activity was observed, promising from the point of view of the intended use of the particles for tumor targeting across the …

Development And Validation Of A Prostate Cancer Genomic Signature That Predicts Early Adt Treatment Response Following Radical Prostatectomy., R. Jeffrey Karnes, Vidit Sharma, Voleak Choeurng, Hussam Al-Deen Ashab, Nicholas Erho, Mohammed Alshalalfa, Bruce Trock, Ashley Ross, Kasra Yousefi, Harrison Tsai, Shuang G. Zhao, Jeffrey J. Tosoian, Zaid Haddad, Mandeep Takhar, S. Laura Chang, Daniel E. Spratt, Firas Abdollah, Robert B. Jenkins, Eric A. Klein, Paul L. Nguyen, Adam P. Dicker, Robert B. Den, Elai Davicioni, Felix Y. Feng, Tamara L. Lotan, Edward M. Schaeffer

Department of Radiation Oncology Faculty Papers

Purpose: Currently, no genomic signature exists to distinguish men most likely to progress on adjuvant androgen deprivation therapy (ADT) after radical prostatectomy for high-risk prostate cancer. Here we develop and validate a gene expression signature to predict response to postoperative ADT.

Experimental Design: A training set consisting of 284 radical prostatectomy patients was established after 1:1 propensity score matching metastasis between adjuvant-ADT (a-ADT)-treated and no ADT–treated groups. An ADT Response Signature (ADT-RS) was identified from neuroendocrine and AR signaling–related genes. Two independent cohorts were used to form three separate data sets for validation (set I, n = 232; set II, …

The Role Of Human Papillomaviruses And Polyomaviruses In Braf-Inhibitor Induced Cutaneous Squamous Cell Carcinoma And Benign Squamoproliferative Lesions, Karin J. Purdie, Charlotte M. Proby, Hasan Rizvi, Heather Griffin, John Doorbar, Mary Sommerlad, Mariet C. Feltkamp, Els Van Der Meijden, Gareth J. Inman, Andrew P. South, Irene M. Leigh, Catherine A. Harwood

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Human papillomavirus (HPV) has long been proposed as a cofactor in the pathogenesis of cutaneous squamous cell carcinoma (cSCC). More recently, the striking clinico-pathological features of cSCCs that complicate treatment of metastatic melanoma with inhibitors targeting BRAF mutations (BRAFi) has prompted speculation concerning a pathogenic role for oncogenic viruses. Here, we investigate HPV and human polyomaviruses (HPyV) and correlate with clinical, histologic, and genetic features in BRAFi-associated cSCC. Materials and Methods: Patients receiving BRAFi treatment were recruited at Barts Health NHS Trust. HPV DNA was detected in microdissected frozen samples using reverse line probe technology and degenerate and nested …

Novel Stat3 Gene Mutation Related Hyper-Ige Syndrome Misdiagnosed As Hidradenitis Suppurativa., Pragya Shrestha, Geetika Sabharwal, Gisoo Ghaffari

Reading Hospital Internal Medicine Residency

Although Hyper-IgE Syndrome (HIES) is a rare immunodeficiency disorder, presenting symptoms may be as common as lung and skin infections. Symptoms are usually nonspecific such as recurrent abscesses, folliculitis, and pneumonias along with skeletal abnormalities. Careful history of susceptibility to skin and lung infections, thorough family history, and findings on physical exam can guide towards the diagnosis of this often-eluded condition. Early optimization of therapy with prophylactic antibiotics can prevent recurrent infections and future complications and improve quality of life and longevity of survival. We present a case of a young female with Hyper-IgE Syndrome with a novel mutation in …

Identification Of Susceptibility Pathways For The Role Of Chromosome 15q25.1 In Modifying Lung Cancer Risk., Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella De Biasi, Younghun Han, Olga Gorlova, Rayjean J Hung, Xifeng Wu, James Mckay, Xuchen Zong, Robert Carreras-Torres, David C Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, Chu Chen, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier A Bertazzi, Angela C Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M Van Der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer Doherty, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Woon-Puay Koh, Yu-Tang Gao, Richard Houlston, John Mclaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, María Soler Artigas, Martin D Tobin, Louise V Wain, Fangyi Gu, Jinyoung Byun, Ahsan Kamal, Dakai Zhu, Rachel F Tyndale, Wei-Qi Wei, Stephen Chanock, Paul Brennan, Christopher I Amos

Articles, Abstracts, and Reports

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated …

Identification Of Susceptibility Pathways For The Role Of Chromosome 15q25.1 In Modifying Lung Cancer Risk, Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella De Biasi, Younghun Han, Olga Gorlova, Rayjean J. Hung, Xifeng Wu, James Mckay, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, Susanne M. Arnold

Markey Cancer Center Faculty Publications

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated …

Cellular Senescence And Their Role In Liver Metabolism In Health And Disease: Overview And Future Directions, Matthew Schade, Jacqueline A. Sanabria, Rodrigo Aguilar, Milad Modarresi, Brad Gillon, Zach Hunter, Jacqueline Fannin, Amrita Mallick, Henri Brunengraber, Juan Sanabria

Surgery

Chronic liver disease has globally risen mainly due to a prevalent Hepatitis C Virus (HCV) infection rate and an epidemic of obesity. It is estimated by the year 2030, 2.2 billion people around the world will be overweight and 1.1 billion people will be obese. Diabetes and obesity are the main risk factors for the development of the metabolic syndrome and in the liver of Non-Alcoholic Fatty Liver Disease (NAFLD) which could progress to NASH related cirrhosis and liver malignancy. At present there is not effective therapy for NASH besides loss of weight and exercise. Furthermore, optimal management of HCC …

Analytical Models Of Neutron Spectral Fluence, Kerma And Absorbed-Dose For Proton Therapy, Suman Shrestha

LSU Master's Theses

Abstract

Purpose: The accurate prediction of stray neutron dose has become increasingly important as it increases the risk of second cancer development after proton therapy. Previously reported analytical models predicted the quantity dose equivalent, which includes physical and biological considerations but does not explicitly take into account material dependence and variation in the radiation quality. The purpose of this study was to investigate the feasibility of an analytical model of absorbed dose to water from stray neutrons in proton therapy.

Methods: To calculate neutron absorbed dose and kerma in water, the authors developed analytical models of neutron spectral fluence and …

Corticosteroid Therapy For Sepsis: A Clinical Practice Guideline, Francois Lamontagne, Bram Rochwerg, Lyubov Lytvyn, Gordon H. Guyatt, Morten Hylander Møller, Djillali Annane, Michelle E. Kho, Neill K J Adhikari, Flavia Machado, Madiha Hashmi

Department of Anaesthesia

No abstract provided.

Disparities In Pulmonary Fibrosis Care In The United States: An Analysis From The Nationwide Inpatient Sample, Adam W. Gaffney, Steffie Woolhander, David Himmelstein, Danny Mccormick

Publications and Research

Background: Idiopathic pulmonary fibrosis is a disease with high morbidity and mortality. Care for these patients, including lung transplantation, may provide significant benefits, but is resource-intensive and expensive. Disadvantaged patients with IPF may hence be at risk for receiving inferior care.

Methods: We analyzed data from the Nationwide Inpatient Sample, a database consisting of all hospitalizations from a 20% sample of US hospitals. We identified adults hospitalized with IPF between 1998 and 2011 using ICD-9 codes. We assessed the effect of insurance coverage and socioeconomic status (SES) on lung transplantation, a treatment that may improve survival. We also examined the …

Prevalence Rates Of Arthritis Among Us Older Adults With Varying Degrees Of Depression: Findings From The 2011 To 2014 National Health And Nutrition Examination Survey, Jessica L. Brooks, Alexander J. Titus, Courtney A. Polenick, Nicole M. Orzechowski, Manney Carrington Reid, Todd A. Mackenzie, Stephen J. Bartels, John A. Batsis

Dartmouth Scholarship

Arthritis and depressive symptoms often interact and negatively influence one another to worsen mental and physical health outcomes. Better characterization of arthritis rates among older adults with different levels of depressive symptoms is an important step toward informing mental health professionals of the need to detect and respond to arthritis and related mental health complications. The primary objective is to determine arthritis rates among US older adults with varying degrees of depression. Using National Health and Nutrition Examination Survey 2011 to 2014 data (N = 4792), we first identified participants aged ≥50 years. Measures screened for depressive symptoms and …

Impact Of Race And Insurance On Door-To-Appendectomy Time Among Pediatric Patients, Carla M. Lopez, Emily R. Christison-Lagay, Daniel Solomon

Journal of Health Disparities Research and Practice

Racial and ethnic disparities in the rate of appendiceal rupture have been widely reported among the pediatric population. The main reasons for this remain largely unknown given that previous explanations pointing to signs of poor health care access have recently been shown to account for only a small percentage of the difference in perforation rates between white and minority children. Because the risk of perforation increases with time, racial disparities in time delay from emergency department presentation to OR appendectomy may help account for the higher appendiceal perforation rates observed among minority children. This is the first study dedicated to …

Modeling The Dynamics Of Human Liver Failure Post Liver Resection, Babita Verma, Pushpavanam Subramaniam, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Liver resection is an important clinical intervention to treat liver disease. Following liver resection, patients exhibit a wide range of outcomes including normal recovery, suppressed recovery, or liver failure, depending on the regenerative capacity of the remnant liver. The objective of this work is to study the distinct patient outcomes post hepatectomy and determine the processes that are accountable for liver failure. Our model based approach shows that cell death is one of the important processes but not the sole controlling process responsible for liver failure. Additionally, our simulations showed wide variation in the timescale of liver failure that is …

Endorepellin Remodels The Endothelial Transcriptome Toward A Pro-Autophagic And Pro-Mitophagic Gene Signature., Thomas Neill, Eva Andreuzzi, Zi-Xuan Wang, Stephen C. Peiper, Maurizo Mongiat, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Regulation of autophagy by proteolytically cleaved fragments of heparan sulfate proteoglycans is a novel and current research focus in tumor biology. Endorepellin is the C-terminal angiostatic fragment of the heparan sulfate proteoglycan perlecan and induces autophagy in endothelial cells. To further investigate this property, we used NanoString, a digital PCR platform for measuring pre-defined transcripts in biological samples to analyze a custom subset of 95 autophagy-related genes in human umbilical vein endothelial cells treated with ultrapure human recombinant endorepellin. We discovered an endorepellin-evoked pro-autophagic and pro-mitophagic gene expression signatures, which included two coordinately up-regulated mitochondrial-associated genes encoding the E3 ubiquitin …

Establishing Hematology And Serum Chemistry Reference Intervals For Wild Hawaiian Monk Seals (Neomonachus Schauinslandi), Angela C. Kaufman, Stacie J. Robinson, Dori L. Borjesson, Michelle Barbieri, Charles L. Littnan

United States Department of Commerce: Staff Publications

Hematology and serum chemistry reference intervals have been previously established for the endangered Hawaiian monk seal (Neomonachus schauinslandi) as an imperative measure for health assessments. Monitoring the health of the wild population depends upon reference intervals that are context specific; hence we developed reference intervals from fresh samples, as opposed to frozen, from wild monk seals. This study builds on the number of parameters from previous efforts by using samples collected between 2004 and 2015 from wild monk seals. Blood samples were analyzed by a single veterinary diagnostic laboratory within 24 hr of collection from apparently healthy, wild …

Maternal Programming: Application Of A Developmental Psychopathology Perspective, Laura M. Glynn, Mariann A. Howland, Molly Fox

Psychology Faculty Articles and Research

The fetal phase of life has long been recognized as a sensitive period of development. Here we posit that pregnancy represents a simultaneous sensitive period for the adult female with broad and persisting consequences for her health and development, including risk for psychopathology. In this review, we examine the transition to motherhood through the lens of developmental psychopathology. Specifically, we summarize the typical and atypical changes in brain and behavior that characterize the perinatal period. We highlight how the exceptional neuroplasticity exhibited by women during this life phase may account for increased vulnerability for psychopathology. Further, we discuss several modes …

An Eqtl Landscape Of Kidney Tissue In Human Nephrotic Syndrome., Christopher E. Gillies, Rosemary Putler, Rajasree Menon, Edgar Otto, Kalyn Yasutake, Viji Nair, Paul Hoover, David Lieb, Shuqiang Li, Sean Eddy, Damian Fermin, Michelle T. Mcnulty, Nephrotic Syndrome Study Network (Neptune), Nir Hacohen, Krzysztof Kiryluk, Matthias Kretzler, Xiaoquan Wen, Matthew G. Sampson, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian "Deterministic Approximation of Posteriors" (DAP) to fine-map …

Training Pediatric Primary Care Providers In Behavior Management Strategies, Kate Burger

Dissertations

Childhood mental health disorders are a significant public health concern in the United States. It is estimated that every year 13 to 20% of children living in the United States experience a mental health disorder (National Research Council and Institute of Medicine, 2009). Despite the clear need for mental health care, less than half (45.6%) of children with one or more emotional, behavioral, or developmental conditions receive treatment from a mental health professional (The National Survey of Children's Health, 2007). There is growing evidence that integrating mental health services into pediatric primary care can result in increased treatment access as …

Dietary Inclusion Of Enriched Chicken Bone Broth Prevents Trigeminal Sensitization Meditated By Early Life Stress, Orion Peterson

Graduate Theses/Dissertations

Early life stress is considered a risk factor for development of migraine, which is a prevalent painful neurological disorder involving sensitization and activation of trigeminal neurons, and irritable bowel syndrome, a condition often comorbid with chronic migraine. The focus of my study was to determine the effects of early life stress and dietary inclusion of enriched chicken bone broth on trigeminal nociceptor sensitization and the gut microbiota. Adult Sprague-Dawley male “sender” rats subjected to primary traumatic stress were placed next to breeding or pregnant female rats that served as “receiver” rats (secondary traumatic stress) and in proximity to the offspring …

Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics And Tumor Cell Movements., Jae Ho Seo, Ekta Agarwal, Kelly G. Bryant, M. Cecilia Caino, Eui Tae Kim, Andrew V. Kossenkov, Hsin-Yao Tang, Lucia R. Languino, Dmitry I. Gabrilovich, Andrew R. Cohen, David W. Speicher, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Syntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission, …