Digital Commons Network^™

Deviations From The Expected Relationship Between Serum Fgf23 And Other Markers In Children With Ckd: A Cross-Sectional Study., Daisy Liu, Ana Catalina Alvarez-Elías, Brooke Wile, Vladimir Belostotsky, Guido Filler

Paediatrics Publications

BACKGROUND: High levels of fibroblast growth factor-23 (FGF23) are associated with mortality. In chronic kidney disease (CKD), FGF23 levels rise as renal function declines. We analyzed the contribution of laboratory values to the variance of FGF23 levels in relationship to a curve of expected FGF23 levels for a given GFR.

METHODS: Following approval by the research ethics boards, we measured FGF23, CysC eGFR, creatinine, urea, albumin, calcium, phosphate, vitamin D metabolites, PTH, alkaline phosphatase, CRP, and venous gases in 141 pediatric CKD patients (45, 37, 32, 13 and 14 CKD stages I, II, III, IV, and V, respectively). Data were …

Pathologists' Diagnosis Of Invasive Melanoma And Melanocytic Proliferations: Observer Accuracy And Reproducibility Study., Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn

Articles, Abstracts, and Reports

No abstract provided.

A Direct In Vivo Comparison Of The Melanocortin Monovalent Agonist Ac-His-Dphe-Arg-Trp-Nh2 Versus The Bivalent Agonist Ac-His-Dphe-Arg-Trp-Pedg20-His-Dphe-Arg-Trp-Nh2: A Bivalent Advantage, Cody J Lensing, Danielle N Adank, Stacey L Wilber, Katie T Freeman, Sathya M Schnell, Robert Charles Speth, Adam T Zarth, Carrie Haskell-Luevano

Faculty Articles

Bivalent ligands targeting putative melanocortin receptor dimers have been developed and characterized in vitro, however studies of their functional in vivo effects have been limited. The current report compares the effects of homobivalent ligand CJL-1-87, Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH₂, to monovalent ligand CJL-1-14, Ac-His-DPhe-Arg-Trp-NH₂ on energy homeostasis in mice after central intracerebroventricular (ICV) administration into the lateral ventricle of the brain. Bivalent ligand CJL-1-87 had noteworthy advantages as an anti-obesity probe over CJL-1-14 in a fasting-refeeding in vivo paradigm. Treatment with CJL-1-87 significantly decreased food intake compared to CJL-1-14 or saline (50% less intake 2 to 8 hours after …

Igf2 Mrna Binding Protein 3 (Imp3) Promotes Glioma Cell Migration By Enhancing The Translation Of Rela/P65., Shruti Bhargava, Abhirami Visvanathan, Vikas Patil, Anuj Kumar, Santosh Kesari, Saumitra Das, Alangar S Hegde, Arimappamagan Arivazhagan, Vani Santosh, Kumaravel Somasundaram

Articles, Abstracts, and Reports

The diffusely infiltrative nature of glioblastoma (GBM) makes them highly recurrent. IGF2 mRNA-binding protein 3 (IMP3), a GBM upregulated RNA binding protein, promotes glioma cell migration. An integrative bioinformatics analysis identified p65 (RELA), a subunit of NF-κB heterodimer as a target and an important mediator of IMP3 promoted glioma cell migration. IMP3 increased p65 protein levels without any change in p65 transcript levels, but promoted its polysome association. RIP-PCR demonstrated the binding of IMP3 to p65 transcript. UV crosslinking experiments with in vitro transcribed RNA confirmed the specific and direct binding of IMP3 to sites on p65 3'UTR. Further, IMP3 …

Ketamine Use For Successful Resolution Of Post-Ercp Acute Pancreatitis Abdominal Pain, S Agerwala, D Sundarapandiyan, Garret Weber

NYMC Faculty Publications

We report a case in which a patient with intractable pain secondary to post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis is successfully treated with a subanesthetic ketamine infusion. Shortly after ERCP, the patient reported severe stabbing epigastric pain. She exhibited voluntary guarding and tenderness without distension. Amylase and lipase levels were elevated. Pain persisted for hours despite hydromorphone PCA, hydromorphone boluses, fentanyl boluses, and postprocedure anxiolytics. Pain management was consulted and a ketamine infusion was trialed, leading to a dramatic reduction in pain. This case suggests that ketamine may be a promising option in treating intractable pain associated with ERCP acute …

Inhibition Of Age-Related Therapy Resistance In Melanoma By Rosiglitazone-Mediated Induction Of Klotho., Reeti Behera, Amanpreet Kaur, Marie R. Webster, Suyeon Kim, Abibatou Ndoye, Curtis H. Kugel, Gretchen M. Alicea, Joshua Wang, Kanad Ghosh, Phil Cheng, Sofia Lisanti, Katie Marchbank, Vanessa Dang, Mitchell Levesque, Reinhard Dummer, Xiaowei Xu, Meenhard Herlyn, Andrew E. Aplin, Alexander Roesch, Cecilia Caino, Dario C. Altieri, Ashani T. Weeraratna

Department of Cancer Biology Faculty Papers

Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical cells in a young microenvironment. This is dependent on age-related secreted factors. Klotho is an age-related protein whose serum levels decrease dramatically by age 40. Most studies on klotho in cancer have focused on the expression of klotho in the tumor cell. We have shown that exogenous klotho inhibits internalization and signaling of Wnt5A, which drives melanoma metastasis and resistance to targeted therapy. We investigate here whether increasing klotho in the aged microenvironment …

Treatment Pathway Of Bone Sarcoma In Children, Adolescents, And Young Adults, Damon R. Reed, Masanori Hayashi, Lars M. Wagner, Odion Binitie, Diana A. Steppan, Andrew S. Brohl, Eric T. Shinohara, Julia A. Bridge, David M. Loeb, Scott C. Borinstein, Michael S. Isakoff

Pediatrics Faculty Publications

When pediatric, adolescent, and young adult patients present with a bone sarcoma, treatment decisions, especially after relapse, are complex and require a multidisciplinary approach. This review presents scenarios commonly encountered in the therapy of bone sarcomas with the goal of objectively presenting a consensus, multidisciplinary management approach. Little variation was found in the authors' group with respect to local control or systemic therapy. Clinical trials were universally prioritized in all settings. Decisions regarding relapse therapies in the absence of a clinical trial had very minor variations initially, but a consensus was reached after a literature review and discussion. This review …

Intracellular Ca 2+ Sensing: Role In Calcium Homeostasis And Signaling, Rafaela Bagur, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Ca²⁺ is a ubiquitous intracellular messenger that controls diverse cellular functions but can become toxic and cause cell death. Selective control of specific targets depends on spatiotemporal patterning of the calcium signal and decoding it by multiple, tunable, and often strategically positioned Ca²⁺-sensing elements. Ca²⁺ is detected by specialized motifs on proteins that have been biochemically characterized decades ago. However, the field of Ca²⁺ sensing has been reenergized by recent progress in fluorescent technology, genetics, and cryo-EM. These approaches exposed local Ca²⁺-sensing mechanisms inside organelles and at the organellar interfaces, revealed how Ca …

Xenon In The Treatment Of Panic Disorder: An Open Label Study., Alexander Dobrovolsky, Thomas E Ichim, Daqing Ma, Santosh Kesari, Vladimir Bogin

Articles, Abstracts, and Reports

BACKGROUND: Current treatments of panic disorder (PD) are limited by adverse effects, poor efficacy, and need for chronic administration. The established safety profile of subanesthetic concentrations of xenon gas, which is known to act as a glutamate subtype NMDA receptor antagonist, coupled with preclinical studies demonstrating its effects in other anxiety related conditions, prompted us to evaluate its feasibility and efficacy in treatment of patients with PD.

METHODS: An open-label clinical trial of xenon-oxygen mixture was conducted in 81 patients with PD; group 1 consisting of patients only with PD (N = 42); and group 2 patients with PD and …

Presurgical Thalamic "Hubness" Predicts Surgical Outcome In Temporal Lobe Epilepsy., Xiaosong He, Gaelle E. Doucet, Dorian Pustina, Michael R. Sperling, Ashwini D. Sharan, Joseph I. Tracy

Department of Neurology Faculty Papers

OBJECTIVE: To characterize the presurgical brain functional architecture presented in patients with temporal lobe epilepsy (TLE) using graph theoretical measures of resting-state fMRI data and to test its association with surgical outcome.

METHODS: Fifty-six unilateral patients with TLE, who subsequently underwent anterior temporal lobectomy and were classified as obtaining a seizure-free (Engel class I, n = 35) vs not seizure-free (Engel classes II-IV, n = 21) outcome at 1 year after surgery, and 28 matched healthy controls were enrolled. On the basis of their presurgical resting-state functional connectivity, network properties, including nodal hubness (importance of a node to the network; …

Early Detection Of Gastric Cancer Using Global, Genome-Wide And Irf4, Elmo1, Clip4 And Msc Dna Methylation In Endoscopic Biopsies, Francesca Pirini, Douglas E. Berg, Et Al

Open Access Publications

Clinically useful molecular tools to triage gastric cancer patients are not currently available. We aimed to develop a molecular tool to predict gastric cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer clinics in low resource settings.We discovered and validated a DNA methylation biomarker panel in endoscopic samples obtained from 362 patients seen between 2004 and 2009 in three high-risk gastric cancer clinics in Lima, Perú, and validated it in 306 samples from the Cancer Genome Atlas project ("TCGA"). Global, epigenome wide and gene-specific DNA methylation analyses were used in a Phase I Biomarker Development Trial to identify a …

Management Of Septic Shock, Rebecca E. Berger, Emanuel Rivers, Mitchell M. Levy

Emergency Medicine Articles

No abstract provided.

Video Game Rehabilitation For Outpatient Stroke (Vigorous): Protocol For A Multi-Center Comparative Effectiveness Trial Of In-Home Gamified Constraint-Induced Movement Therapy For Rehabilitation Of Chronic Upper Extremity Hemiparesis., Lynne V Gauthier, Chelsea Kane, Alexandra Borstad, Nancy Strahl, Gitendra Uswatte, Edward Taub, David Morris, Alli Hall, Melissa Arakelian, Victor Mark

Articles, Abstracts, and Reports

BACKGROUND: Constraint-Induced Movement therapy (CI therapy) is shown to reduce disability, increase use of the more affected arm/hand, and promote brain plasticity for individuals with upper extremity hemiparesis post-stroke. Randomized controlled trials consistently demonstrate that CI therapy is superior to other rehabilitation paradigms, yet it is available to only a small minority of the estimated 1.2 million chronic stroke survivors with upper extremity disability. The current study aims to establish the comparative effectiveness of a novel, patient-centered approach to rehabilitation utilizing newly developed, inexpensive, and commercially available gaming technology to disseminate CI therapy to underserved individuals. Video game delivery of …

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark Faries, John F Thompson, Alistair J Cochran, Robert H Andtbacka, Nicola Mozzillo, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Alessandro Testori, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W J M Wouters, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R Rossi, Rogerio I Neves, Steven D Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B Johnson, Patrick Terheyden, Adam C Berger, Tara L Huston, Jeffrey D Wayne, B Mark Smithers, Heather B Neuman, Schlomo Schneebaum, Jeffrey E Gershenwald, Charlotte E Ariyan, Darius C Desai, Lisa Jacobs, Kelly M Mcmasters, Anja Gesierich, Peter Hersey, Steven D Bines, John M Kane, Richard J Barth, Gregory Mckinnon, Jeffrey M Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A Hoefer, James M Lewis, Randall Scheri, Mark C Kelley, Omgo E Nieweg, R Dirk Noyes, Dave S B Hoon, He-Jing Wang, David A Elashoff, Robert M Elashoff

Articles, Abstracts, and Reports

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark B. Faries, John F. Thompson, Alistair J. Cochran, Robert H. Andtbacka, Nicola Mozzillo, Jonathan S. Zager, Tiina Jahkola, Tawnya L. Bowles, Alessandro Testori, Peter D. Beitsch, Harald J. Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W.J.M. Wouters, Michael S. Sabel, Edward A. Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R. Rossi, Rogerio I. Neves, Steven D. Trocha, Frances Wright, David R. Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B. Johnson, Patrick Terheyden, Adam C. Berger, Tara L. Huston, Jeffrey D. Wayne, B. Mark Smithers, Heather B. Neuman, Schlomo Schneebaum, Jeffrey E. Gershenwald, Charlotte E. Ariyan, Darius C. Desai, Lisa Jacobs, Kelly M. Mcmasters, Anja Gesierich, Peter Hersey, Steven D. Bines, John M. Kane, Richard J. Barth, Gregory Mckinnon, Jeffrey M. Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A. Hoefer, James M Lewis, Randall Scheri, Mark C. Kelley, Omgo E. Nieweg, R. Dirk Noyes, Dave S.B. Hoon, He-Jing Wang, David A. Elashoff, Robert M. Elashoff

Department of Surgery Faculty Papers

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

Obesity, Metabolic Factors And Risk Of Different Histological Types Of Lung Cancer: A Mendelian Randomization Study, Robert Carreras-Torres, Mattias Johansson, Philip C. Haycock, Kaitlin H. Wade, Caroline L. Relton, Richard M. Martin, George Davey Smith, Demetrius Albanes, Melinda C. Aldrich, Angeline Andrew, Susanne M. Arnold, Heike Bickeböller, Stig E. Bojesen, Hans Brunnström, Jonas Manjer, Irene Brüske, Neil E. Caporaso, Chu Chen, David C. Christiani, Warren Jay Christian, Jennifer A. Doherty, Eric J. Duell, John K. Field, Michael P. A. Davies, Michael W. Marcus, Gary E. Goodman, Kjell Grankvist, Aage Haugen, Yun-Chul Hong, Lambertus A. Kiemeney

Markey Cancer Center Faculty Publications

Background

Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.

Methods and findings

We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of …

Nfatc2 Modulates Microglial Activation In The Aβpp/Ps1 Mouse Model Of Alzheimer's Disease, Gunjan D. Manocha, Atreyi Ghatak, Kendra L. Puig, Susan D. Kraner, Christopher M. Norris, Colin K. Combs

Pharmacology and Nutritional Sciences Faculty Publications

Alzheimer’s disease (AD) brains are characterized by fibrillar amyloid-β (Aβ) peptide containing plaques and associated reactive microglia. The proinflammatory phenotype of the microglia suggests that they may negatively affect disease course and contribute to behavioral decline. This hypothesis predicts that attenuating microglial activation may provide benefit against disease. Prior work from our laboratory and others has characterized a role for the transcription factor, nuclear factor of activated T cells (NFAT), in regulating microglial phenotype in response to different stimuli, including Aβ peptide. We observed that the NFATc2 isoform was the most highly expressed in murine microglia cultures, and inhibition or …

Prevalence And Prognostic Features Of Ecg Abnormalities In Acute Stroke: Findings From The Siren Study Among Africans, Abiodun M. Adeoye, Okechukwu S. Ogah, Bruce Ovbiagele, Rufus Akinyemi, Vincent Shidali, Francis Agyekum, Akinyemi Aje, Oladimeji Adebayo, Joshua O. Akinyemi, Philip Kolo, Lambert Tetteh Appiah, Henry Iheonye, Uwanuruochi Kelechukwu, Amusa Ganiyu, Taiwo O. Olunuga, Onoja Akpa, Ojo Olakanmi Olagoke, Fred Stephen Sarfo, Kolawole Wahab, Samuel Olowookere, Adekunle Fakunle, Albert Akpalu, Philip B. Adebayo, Kwadwo Nkromah, Joseph Yaria, Philip Ibinaiye, Godwin Ogbole, Aridegbe Olumayowa, Sulaiman Lakoh, Benedict Calys-Tagoe, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

Africa has a growing burden of stroke with associated high morbidity and a 3-year fatality rate of 84%. Cardiac disease contributes to stroke occurrence and outcomes, but the precise relationship of abnormalities as noted on a cheap and widely available test, the electrocardiogram (ECG), and acute stroke outcomes have not been previously characterized in Africans.

Objectives

The study assessed the prevalence and prognoses of various ECG abnormalities among African acute stroke patients encountered in a multisite, cross-national epidemiologic study.

Methods

We included 890 patients from Nigeria and Ghana with acute stroke who had 12-lead ECG recording within first 24 …

Genetic Associations With Lipoprotein Subfraction Measures Differ By Ethnicity In The Multi-Ethnic Study Of Atherosclerosis (Mesa), Zhe Wang, Ani Manichukal, David C. Goff, Samia Mora, Jose M. Ordovas, Nicholas M. Pajewski, Wendy S. Post, Jerome I. Rotter, Michele M. Sale, Stephanie A. Santorico, David Siscovick, Michael Y. Tsai, Donna K. Arnett, Stephen Rich, Alexis C. Frazier-Wood

Epidemiology and Environmental Health Faculty Publications

A recent genome-wide association study associated 62 single nucleotide polymorphisms (SNPs) from 43 genomic loci, with fasting lipoprotein subfractions in European–Americans (EAs) at genome-wide levels of significance across three independent samples. Whether these associations are consistent across ethnicities with a non-European ancestry is unknown. We analyzed 15 lipoprotein subfraction measures, on 1677 African–Americans (AAs), 1450 Hispanic–Americans (HAs), and 775 Chinese–Americans (CHN) participating in the multi-ethnic study of atherosclerosis (MESA). Genome-wide data were obtained using the Affymetrix 6.0 and Illumina HumanOmni chips. Linear regression models between genetic variables and lipoprotein subfractions were adjusted for age, gender, body mass index, smoking, study …

Exploring Overlaps Between The Genomic And Environmental Determinants Of Lvh And Stroke: A Multicenter Study In West Africa, Abiodun M. Adeoye, Bruce Ovbiagele, Philip Kolo, Lambert Appiah, Akinyemi Aje, Oladimeji Adebayo, Fred Sarfo, Joshua Akinyemi, Gregory Adekunle, Francis Agyekum, Vincent Shidali, Okechukwu Ogah, Dan Lackland, Mulugeta Gebregziabher, Donna K. Arnett, Hemant K. Tiwari, Rufus Akinyemi, Ojo Olakanmi Olagoke, Ayodipupo Sikiru Oguntade, Taiwo Olunuga, Kelechi Uwanruochi, Carolyn Jenkins, Patrick Adadey, Henry Iheonye, Lukman Owolabi, Reginald Obiako, Samuel Akinjopo, Kevin Armstrong, Albert Akpalu, Adekunle Fakunle

Epidemiology and Environmental Health Faculty Publications

Background

Whether left ventricular hypertrophy (LVH) is determined by similar genomic and environmental risk factors with stroke, or is simply an intermediate stroke marker, is unknown.

Objectives

We present a research plan and preliminary findings to explore the overlap in the genomic and environmental determinants of LVH and stroke among Africans participating in the SIREN (Stroke Investigative Research and Education Network) study.

Methods

SIREN is a transnational, multicenter study involving acute stroke patients and age-, ethnicity-, and sex-matched control subjects recruited from 9 sites in Ghana and Nigeria. Genomic and environmental risk factors and other relevant phenotypes for stroke and …

A Mathematical Formula For Institutional Gme Program Support, Kimberly Baker-Genaw, Crystal Gyiraszin

Graduate Medical Education Articles

No abstract provided.

Ginseng And Obesity: Observations And Understanding In Cultured Cells, Animals And Humans, Longyun Zhang, Carlos Virgous, Hongwei Si

Human Sciences Faculty Research

Ginseng, a traditional medical herb, has been reported having beneficial effects in fatigue, heart diseases, diabetes, immune function and erectile dysfunction. In recent years, increasing investigations have been conducted on ginseng in preventing and treating of obesity, one of the major worldwide escalating public health concerns. However, the effect and the relevant mechanisms behind how ginseng works as an antiobesity treatment are still controversial. In this review, we briefly discussed the chemical structures, metabolism and pharmacokinetics of ginseng and its major bioactive components ginsenosides. The major focus is on the antiobesity effects and the physiological, cellular and molecular mechanisms of …

Sofosbuvir, Velpatasvir, And Voxilaprevir For Previously Treated Hcv Infection, Marc Bourlière, Stuart C. Gordon, Steven L. Flamm, Curtis L. Cooper, Alnoor Ramji, Myron Tong, Natarajan Ravendhran, John M. Vierling, Tram T. Tran, Stephen Pianko, Meena B. Bansal, Victor De Lédinghen, Robert H. Hyland, Luisa M. Stamm, Hadas Dvory-Sobol, Evguenia Svarovskaia, Jie Zhang, K C. Huang, G M. Subramanian, Diana M. Brainard, John G. Mchutchison, Elizabeth C. Verna, Peter Buggisch, Charles S. Landis, Ziad H. Younes, Michael P. Curry, Simone I. Strasser, Eugene R. Schiff, K R. Reddy, Michael P. Manns, Kris V. Kowdley, Stefan Zeuzem

Gastroenterology Articles

BACKGROUND: Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options.

METHODS: We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) …

C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non‐coding RNAs that have been long known to perform 2′‐O‐methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader‐Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre‐mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD …

Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng

Articles, Abstracts, and Reports

A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non-small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 …

Cross-Talk Between Clinical And Host-Response Parameters Of Periodontitis In Smokers, Radha Nagarajan, Craig S. Miller, Dolph R. Dawson Iii, Mohanad Al-Sabbagh, Jeffrey L. Ebersole

Institute for Biomedical Informatics Faculty Publications

Background and Objective

Periodontal diseases are a major public health concern leading to tooth loss and have also been shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for the development of numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies regarding susceptibility to disease associated with smoking. This investigation focused on identifying differences in four broad sets of variables, consisting of: (i) host‐response molecules; (ii) periodontal clinical parameters; (iii) antibody responses to periodontal pathogens …

Pain Perception In Latino Vs. Caucasian And Male Vs. Female Patients: Is There Really A Difference?, Molly Aufiero, Holly Stankewicz, Shaila Quazi, Jeanne Jacoby, Jill Stoltzfus

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

INTRODUCTION: Pain is a common emergency department (ED) complaint. It is important to understand the differences in pain perception among different ethnic and demographic populations.

METHODS: We applied a standardized painful stimulus to Caucasian and Latino adult patients to determine whether the level of pain reported differed depending on ethnicity (N=100; 50 Caucasian [C], 50 Latino [L] patients) and gender (N=100; 59 female, 41 male). Patients had an initial pain score of 0 or 1. A blood pressure cuff was inflated 20 mm HG above the patient's systolic blood pressure and held for three minutes. Pain scores, using both a …

Salivary And Serum Adiponectin And C-Reactive Protein Levels In Acute Myocardial Infarction Related To Body Mass Index And Oral Health, Jeffrey L. Ebersole, Richard J. Kryscio, C. Campbell, D. F. Kinane, J. Mcdevitt, N. Christodoulides, P. N. Floriano, Craig S. Miller

Oral Health Practice Faculty Publications

Background and Objective

Adiponectin is produced by adipose cells and is considered an anti‐inflammatory molecule. In contrast, C‐reactive protein (CRP) has been identified as a hallmark of systemic inflammation and used as a risk marker of cardiovascular disease (CVD). Of interest was the relationship of these two biomarkers to oral health and CVD risk.

Material and Methods

This investigation examined these two molecules in serum and unstimulated whole saliva of patients within 48 h of an acute myocardial infarction (AMI) compared to control subjects. We hypothesized a differential response in these biomolecules resulting from the heart attack that would be …

An Extended Vascular Model For Less Biased Estimation Of Permeability Parameters In Dce-T1 Images, Siamak P. Nejad-Davarani, Hassan Bagher-Ebadian, James R. Ewing, Douglas C. Noll, Tom Mikkelsen, Michael Chopp, Quan Jiang

Neurology Articles

One of the key elements in dynamic contrast enhanced (DCE) image analysis is the arterial input function (AIF). Traditionally, in DCE studies a global AIF sampled from a major artery or vein is used to estimate the vascular permeability parameters; however, not addressing dispersion and delay of the AIF at the tissue level can lead to biased estimates of these parameters. To find less biased estimates of vascular permeability parameters, a vascular model of the cerebral vascular system is proposed that considers effects of dispersion of the AIF in the vessel branches, as well as extravasation of the contrast agent …

The Quest For Sustained Multiple Morbidity Reduction In Very Low-Birth-Weight Infants: The Antifragility Project., Joseph Kaempf, N M Schmidt, S Rogers, C Novack, M Friant, L Wang, N Tipping

Articles, Abstracts, and Reports

OBJECTIVE: Can a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities?

STUDY DESIGN: Prospectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always …