Medical Specialties Commons^™

Testing The Prognostic Accuracy Of The Updated Pediatric Sepsis Biomarker Risk Model, Hector R. Wong, Scott L. Weiss, John S. Giuliano Jr., Mark S. Wainwright, Robert J. Freishtat, +20 Additional Authors

Pediatrics Faculty Publications

Background

We previously derived and validated a risk model to estimate mortality probability in children with septic shock (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl). PERSEVERE uses five biomarkers and age to estimate mortality probability. After the initial derivation and validation of PERSEVERE, we combined the derivation and validation cohorts (n = 355) and updated PERSEVERE. An important step in the development of updated risk models is to test their accuracy using an independent test cohort.

Objective

To test the prognostic accuracy of the updated version PERSEVERE in an independent test cohort.

Methods

Study subjects were recruited from multiple pediatric intensive …

Consanguineous Marriage And Intellectual And Developmental Disabilities Among Arab Bedouins Children Of The Negev Region In Southern Israel: A Pilot Study, Hassan Abu Saad, Salman Elbedour, Eyad Hallaq, Joav Merrick, Ariel Tenenbaum

Pediatrics Faculty Publications

No abstract provided.

Human And Helicobacter Pylori Coevolution Shapes The Risk Of Gastric Disease, Nuri Kodaman, Alvaro Pazos, Barbara G. Schneider, M. Blanca Piazuelo, Robertino Mera, Rafal S. Sobota

Dartmouth Scholarship

Helicobacter pylori is the principal cause of gastric cancer, the second leading cause of cancer mortality worldwide. However, H. pylori prevalence generally does not predict cancer incidence. To determine whether coevolution between host and pathogen influences disease risk, we examined the association between the severity of gastric lesions and patterns of genomic variation in matched human and H. pylori samples. Patients were recruited from two geographically distinct Colombian populations with significantly different incidences of gastric cancer, but virtually identical prevalence of H. pylori infection. All H. pylori isolates contained the genetic signatures of multiple ancestries, with an ancestral African cluster …

Relationships Between Parenting Self-Efficacy And Distress In Parents With And Without Cancer, Julie Marie Cessna

USF Tampa Graduate Theses and Dissertations

Despite the relatively large number of parents with cancer, relatively little is known about the extent to which having cancer affects the parenting experience. Qualitative studies have identified issues and concerns that create distress among parents with cancer, but quantitative studies have yet to be conducted. Studies demonstrate that parents with cancer experience psychological distress, and that parenting self-efficacy is related to psychological distress among parents without cancer. However, no study to date has examined the relationships between parenting self-efficacy and psychological distress among parents with cancer. This study sought to address these gaps in the literature by comparing parents …

Two Distinct Dynamic Modes Subtend The Detection Of Unexpected Sounds, Jean-Rémi King, Alexandre Gramfort, Aaron Schurger, Lionel Naccache, Stanislas Dehaene

Psychology Faculty Articles and Research

The brain response to auditory novelty comprises two main EEG components: an early mismatch negativity and a late P300. Whereas the former has been proposed to reflect a prediction error, the latter is often associated with working memory updating. Interestingly, these two proposals predict fundamentally different dynamics: prediction errors are thought to propagate serially through several distinct brain areas, while working memory supposes that activity is sustained over time within a stable set of brain areas. Here we test this temporal dissociation by showing how the generalization of brain activity patterns across time can characterize the dynamics of the underlying …

Emerging Challenges And Health System Capacity: The Case Of Non- Communicable Diseases In Pakistan; A Review, Mubashir Zafar, Muhammad Ashar Malik

Community Health Sciences

Background: Pakistan is facing double burden of disease and the contribution of mortality by non-communicable diseases has over numbered the communicable diseases. The focus of health system of Pakistan is inclined more towards communicable disease and maternal & child health. Therefore, there is a need to review health policy, health sector budgeting and health setup in order to meet the needs of healthcare in context of non-communicable disease.

Objective: To review the health system capacity to manage the emerging challenge of non-communicable diseases in Pakistan.

Methodology: A thorough literature search on PubMed and Google Scholar was done. Reports from W.H.O, …

2014 Founders' Day, Philadelphia College Of Osteopathic Medicine

Founders Day Programs

The 2014 Founders Day OJ Snyder Memorial Medal recipient was Matthew Schure, PhD. The Philadelphia Campus Mason W Pressly Memorial Medal Recipient was Matthew Spiecher (DO '14). The Georgia campus Mason W Pressly Memorial Medal Recipient was Jason Milton, (DO '14) PharmD, MBA

Update On Ranolazine In The Management Of Angina., J Nicolás Codolosa, Subroto Acharjee, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Mortality rates attributable to coronary heart disease have declined in recent years, possibly related to changes in clinical presentation patterns and use of proven secondary prevention strategies. Chronic stable angina (CSA) remains prevalent, and the goal of treatment is control of symptoms and reduction in cardiovascular events. Ranolazine is a selective inhibitor of the late sodium current in myocytes with anti-ischemic and metabolic properties. It was approved by the US Food and Drug Administration in 2006 for use in patients with CSA. Multiple, randomized, placebo-controlled trials have shown that ranolazine improves functional capacity and decreases anginal episodes in CSA patients, …

Regulation Of The Proapoptotic Functions Of Prostate Apoptosis Response-4 (Par-4) By Casein Kinase 2 In Prostate Cancer Cells, A De Thonel, A Hazoumé, V Kochin, K Isoniemi, G Jego, E Fourmaux, A Hammann, H Mjahed, O Filhol, O Micheau, P Rocchi, V Mezger, J E Eriksson, Vivek M. Rangnekar, C Garrido

Radiation Medicine Faculty Publications

The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 supports survival is far from complete. In this work, we demonstrate both in rat and humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii) phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel different levels of CK2-dependent regulation of Par-4 between species. In rats, the phosphorylation by CK2 at …

Maternal Biomarkers Of Endothelial Dysfunction And Preterm Delivery, Xinhua Chen, Theresa O Scholl

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Endothelial dysfunction is key to the development of atherosclerosis. Preterm delivery foreshadows later maternal cardiovascular disease (CVD), but it is not known if endothelial dysfunction also occurs. We prospectively measured circulating biomarkers of endothelial dysfunction in pregnant women with preterm or term delivery.

METHODS: We conducted a case-control study nested within a large prospective epidemiological study of young, generally healthy pregnant women. Women who delivered preterm (gestation, n = 240) and controls who delivered at term (n = 439) were included. Pregnancies complicated by preeclampsia were analyzed separately. Circulating endothelial dysfunction biomarkers included soluble intercellular adhesion molecule-1 (sICAM-1), vascular …

Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro

Faculty Publications & Research

Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, …

Management Of Benign Paroxysmal Positional Vertigo: A Randomized Controlled Trial, Regina Sacco Dpt, Ba, Bhsc, David B. Burmeister Do, Facep, Valerie Rupp Rn, Bsn, Marna R. Greenberg Do, Mph, Facep

Department of Emergency Medicine

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is a common presenting problem.

OBJECTIVE: Our aim was to compare the efficacy of vestibular rehabilitation (maneuver) vs. conventional therapy (medications) in patients presenting to the emergency department (ED) with BPPV.

METHODS: This was a prospective, single-blinded physician, randomized pilot study comparing two groups of patients who presented to the ED with a diagnosis of BPPV at a Level 1 trauma center with an annual census of approximately 75,000. The first group received standard medications and the second group received a canalith repositioning maneuver. The Dizziness Handicap Inventory was used to measure symptom resolution. …

Response Of An Aggressive Periosteal Aneurysmal Bone Cyst (Abc) Of The Radius To Denosumab Therapy., Chantal Pauli, Bruno Fuchs, Christian Pfirrmann, Julia A. Bridge, Silvia Hofer, Beata Bode

Journal Articles: Pathology and Microbiology

Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the …

Zinc Deficiency-Associated Dermatitis In Infants During A Nationwide Shortage Of Injectable Zinc--Washington, Dc, And Houston, Texas 2012-2013, Duke Ruktanonchai, Michael Lowe, Scott A. Norton, Tiana Garrett, Lamia Soghier, Edward Weiss, June Hatfield, Jeffrey Lapinski, Steven Abrams, Wanda Barfield

Pediatrics Faculty Publications

No abstract provided.

Early Quick Acuity Score Provides More Complete Data On Emergency Department Walkouts., Paris B Lovett, Md, J Akiva Kahn, Md, Stuart E Greene, Md, Matthew A Bloch, Md, Daniel R Brandt, Md, Michael R Minckler, Md

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Many prior studies have compared the acuity of Emergency Department (ED) patients who have Left Without Being Seen (LWBS) against non-LWBS patients. A weakness in these studies is that patients may walk out prior to the assignment of a triage score, biasing comparisons. We report an operational change whereby acuity was assessed immediately upon patient arrival. We hypothesized more patients would receive acuity scores with EQAS. We also sought to compare LWBS and non-LWBS patient characteristics with reduced bias.

SETTING: urban, academic medical center. Retrospective cohort study, electronic chart review, collecting data on all ED patients presenting between 4/1/2010 …

An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan

Dartmouth Scholarship

While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls …

An Efficient, Free-Breathing Protocolf For Mr Right Heart Catheterization, Jonathan R. Mazal, Toby Rogers, Anthony Z. Faranesh, Peter Kellman, William H. Schenke, Annette M. Stine, Laurie P. Grant, Kanishka Ratnayaka, Robert J. Lederman

Pediatrics Posters and Presentations

No abstract provided.

Technologist Primer For Mri Right Heart Catheterization: The Nih And Cnmc Experience, Jonathan R. Mazal, Kendall O'Brien, William Schenke, Annette Stine, Laurie Grant, Anthony Z. Faranesh, Kanishka Ratnayaka, Robert J. Lederman

Pediatrics Posters and Presentations

No abstract provided.

Quantification Of Right Ventricular Function From Short-Axis Displacement-Encoded Images, Jonathan D. Suever, Gregory J. Wehner, Linyuan Jing, David K. Powell, Christopher M. Haggerty, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Presentations

Background

Right ventricular (RV) function is important in many disease states, but is difficult to quantify from routine MR imaging. Previous work has shown that long-axis deformation/strain is the most critical contributor to global RV function; however, short-axis datasets allow for better coverage of the RV. Thus it would be ideal to be able to quantify RV long-axis function using short-axis slice orientations. We hypothesized that a stack of three-dimensional (3D) displacement encoded (DENSE) images could reliably quantify longitudinal deformation of the RV to overcome the need for acquiring additional long-axis views of the RV.

Methods

A contiguous stack of …

Assessment Of Intra- And Inter-Ventricular Cardiac Dyssynchrony In Patients With Repaired Tetralogy Of Fallot: A Cardiac Magnetic Resonance Study, Linyuan Jing, Christopher M. Haggerty, Jonathan D. Suever, Ashwin Prakash, Frank Cecchin, Oskar Skrinjar, Tal Geva, Andrew J. Powell, Brandon K. Fornwalt

Pediatrics Presentations

Background

Patients with repaired tetralogy of Fallot (TOF) frequently have right bundle branch block. However, the contribution of cardiac dyssynchrony to dysfunction remains controversial. To better understand this phenomenon and ultimately study therapies, we developed a method to quantify left (LV), right (RV) and inter-ventricular cardiac dyssynchrony using standard cine CMR.

Methods

30 patients with repaired TOF (age 28 ± 16, 46% female) and 17 healthy controls (age 29 ± 7, 12% female) underwent cine CMR. Patients were imaged twice to assess inter-test reproducibility. Circumferential strain vs time curves were generated with a custom feature tracking algorithm for 12 LV …

Two-Dimensional Estimates Of Left Ventricular Strains Are Significantly Affected By Through-Plane Motion, Jonathan D. Suever, Gregory J. Wehner, Linyuan Jing, David K. Powell, Christopher M. Haggerty, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Presentations

Background

Advanced measures of cardiac mechanics such as left ventricular (LV) strains can be used in conjunction with classical biomarkers to gauge cardiovascular health and improve prediction of patient outcomes. Several imaging techniques, including displacement-encoded magnetic resonance imaging (DENSE), are used to non-invasively assess cardiac mechanics. These data are predominantly acquired in two dimensions (2D) due to simplified post-processing and shorter acquisition times; however, this type of acquisition and subsequent analysis cannot account for through-plane motion caused by longitudinal contraction of the left ventricle. We hypothesized that through-plane motion has a significant effect on 2D strain estimates.

Methods

Cine DENSE …

Characterizing The Temporal Evolution Of Altered Cardiac Mechanics In Diet-Induced Obese Mice Using Cine Dense Cmr, Christopher M. Haggerty, Andrea C. Mattingly, Cassi M. Binkley, Sage P. Kramer, David K. Powell, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Presentations

Background

Obesity and metabolic syndrome are associated with increased risk of cardiovascular disease. Research suggests that altered cardiac mechanics (i.e., reduced strains, torsion, and synchrony of contraction) are present in obesity; yet, the causes of this mechanical dysfunction and its relationship to other sequelae of obesity (e.g., hypertension and elevated blood glucose) are not well understood. We hypothesize that diet-induced obesity in mice leads to reductions in measures of left ventricular (LV) mechanics, which develop in acute response to the onset of hyperglycemia, hypertension, and ventricular remodeling.

Methods

Twenty 4-week-old C57BL/6J mice were randomized (n = 10 per group) to …

Sodium-Coupled Neutral Amino Acid Transporter 1 (Snat1) Modulates L-Citrulline Transport And Nitric Oxide (No) Signaling In Piglet Pulmonary Arterial Endothelial Cells, Anna Dikalova, Angela Fagiana, Judy L. Aschner, Michael Aschner, Marshall Summar, Candice D. Fike

Pediatrics Faculty Publications

Rationale

There is evidence that impairments in nitric oxide (NO) signaling contribute to chronic hypoxia-induced pulmonary hypertension. The L-arginine-NO precursor, L-citrulline, has been shown to ameliorate pulmonary hypertension. Sodium-coupled neutral amino acid transporters (SNATs) are involved in the transport of L-citrulline into pulmonary arterial endothelial cells (PAECs). The functional link between the SNATs, L-citrulline, and NO signaling has not yet been explored.

Objective

We tested the hypothesis that changes in SNAT1 expression and transport function regulate NO production by modulating eNOS coupling in newborn piglet PAECs.

Methods and Results

A silencing RNA (siRNA) technique was used to assess the contribution …

A Safety Mnemonic For Pediatric Oncology Patients: Knowledge, Confidence And Skills Accuracy During Simulation, Luanne Linnard-Palmer, Barbara Ganley

Collected Faculty Scholarship

Cancer is the second leading cause of death in the United States, surpassed only by heart disease [1]. Approximately 1.6 million Americans will receive treatment for a variety of cancers annually [2]. This increase in oncology nursing care opportunities highlights the need to ensure that nurses have the skills, knowledge, and tools that allow them to safely provide care. Because Undergraduate nursing education often does not provide in-depth coverage of the principles of safe oncology nursing care required for children or adults, this study addressed protocols used when caring for chemotherapy pediatric patients using a chemotherapy mnemonic. The purpose of …

Identification Of A Developmental Gene Expression Signature, Including Hox Genes, For The Normal Human Colonic Crypt Stem Cell Niche: Overexpression Of The Signature Parallels Stem Cell Overpopulation During Colon Tumorigenesis., Seema Bhatlekar, Sankar Addya, Moreh Salunek, Christopher R Orr, Saul Surrey, Steven E. Mckenzie, Jeremy Z Fields, Bruce M Boman

Kimmel Cancer Center Faculty Papers

Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, …

Metabolic Effects Of Acute Thiamine Depletion Are Reversed By Rapamycin In Breast And Leukemia Cells, Shuqian Liu, Sumitra Miriyala, Mignon A Keaton, Craig T. Jordan, Christina Wiedl, Daret K. St Clair, Jeffrey A. Moscow

Pediatrics Faculty Publications

Thiamine-dependent enzymes (TDEs) control metabolic pathways that are frequently altered in cancer and therefore present cancer-relevant targets. We have previously shown that the recombinant enzyme thiaminase cleaves and depletes intracellular thiamine, has growth inhibitory activity against leukemia and breast cancer cell lines, and that its growth inhibitory effects were reversed in leukemia cell lines by rapamycin. Now, we first show further evidence of thiaminase therapeutic potential by demonstrating its activity against breast and leukemia xenografts, and against a primary leukemia xenograft. We therefore further explored the metabolic effects of thiaminase in combination with rapamycin in leukemia and breast cell lines. …

Then And Now: The Progress In Hepatitis B Treatment Over The Past 20 Years., Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this …

Paracrine Apoptotic Effect Of P53 Mediated By Tumor Suppressor Par-4, Ravshan Burikhanov, Tripti Shrestha-Bhattarai, Nikhil Hebbar, Shirley Qiu, Yanming Zhao, Gerard P. Zambetti, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53⁻/⁻ or Par-4⁻/⁻ mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 …

Prognosis Of Differentiated Thyroid Cancer In Relation To Serum Thyrotropin And Thyroglobulin Antibody Status At Time Of Diagnosis, Donald S. A. Mcleod, David S. Cooper, Paul W. Ladenson, Kenneth B. Ain, James D. Brierley, Henry G. Fein, Bryan R. Haugen, Jacqueline Jonklaas, James Magner, Douglas S. Ross, Monica C. Skarulis, David L. Steward, Harry R. Maxon, Steven I. Sherman

Internal Medicine Faculty Publications

BACKGROUND: Serum thyrotropin (TSH) concentration and thyroid autoimmunity may be of prognostic importance in differentiated thyroid cancer (DTC). Preoperative serum TSH level has been associated with higher DTC stage in cross-sectional studies; data are contradictory on the significance of thyroid autoimmunity at the time of diagnosis.

OBJECTIVE: We sought to assess whether preoperative serum TSH and perioperative antithyroglobulin antibodies (TgAb) were associated with thyroid cancer stage and outcome in DTC patients followed by the National Thyroid Cancer Treatment Cooperative Study, a large multicenter thyroid cancer registry.

METHODS: Patients registered after 1996 with available preoperative serum TSH (n=617; the TSH cohort) …

Estimation Of Daily Interfractional Larynx Residual Setup Error After Isocentric Alignment For Head And Neck Radiotherapy: Quality Assurance Implications For Target Volume And Organs-At-Risk Margination Using Daily Ct On- Rails Imaging., Charles A Baron, Musaddiq J Awan, Abdallah S R Mohamed, Imad Akel, David I Rosenthal, G Brandon Gunn, Adam S Garden, Brandon A Dyer, Laurence Court, Parag R Sevak, Esengul Kocak-Uzel, Clifton D Fuller

Department of Medicine Faculty Papers

Larynx may alternatively serve as a target or organs at risk (OAR) in head and neck cancer (HNC) image-guided radiotherapy (IGRT). The objective of this study was to estimate IGRT parameters required for larynx positional error independent of isocentric alignment and suggest population-based compensatory margins. Ten HNC patients receiving radiotherapy (RT) with daily CT on-rails imaging were assessed. Seven landmark points were placed on each daily scan. Taking the most superior-anterior point of the C5 vertebra as a reference isocenter for each scan, residual displacement vectors to the other six points were calculated postisocentric alignment. Subsequently, using the first scan …