Medicine and Health Sciences Commons^™

Pharmacologic Or Genetic Targeting Of Glutamine Synthetase Skews Macrophages Toward An M1-Like Phenotype And Inhibits Tumor Metastasis., Erika M. Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, D Craig Hooper, Wouter H. Lamers, Bart Ghesquière, Daniel W. Mcvicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna

Department of Cancer Biology Faculty Papers

Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial …

Chiari I Malformation And Spinal Cord Ischemia In A Cadaver., Faizullah Mashriqi, Marios Loukas, Rod J Oskouian, Anthony V D'Antoni, R Shane Tubbs

Articles, Abstracts, and Reports

With advanced imaging, the Chiari I malformation (CIM) is more frequently diagnosed than in the past when this entity was identified most commonly at autopsy. Herein, we report the rare case of an adult cadaver found not only to have CIM but also adjacent spinal cord ischemia. This case is discussed in the context of chronic compression of the spinal cord by a CIM and the need for close monitoring of these patients.

Epigenetic Regulation Of Kpc1 Ubiquitin Ligase Affects The Nf-Κb Pathway In Melanoma., Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave S B Hoon

Articles, Abstracts, and Reports

Purpose: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of the NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma.Experimental Design: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue microarrays; n = 137, JWCI cohort; n = 40) and The Cancer Genome Atlas database (TCGA …

Selective Inhibitors Of Human Mpges-1 From Structure-Based Computational Screening, Ziyuan Zhou, Yaxia Yuan, Shuo Zhou, Kai Ding, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Human mPGES-1 is recognized as a promising target for next generation of anti-inflammatory drugs. Although various mPGES-1 inhibitors have been reported in literature, few have entered clinical trials and none has been proven clinically useful so far. It is highly desired for developing the next generation of therapeutics for inflammation-related diseases to design and discover novel inhibitors of mPGES-1 with new scaffolds. Here, we report the identification of a series of new, potent and selective inhibitors of human mPGES-1 with diverse scaffolds through combined computational and experimental studies. The computationally modeled binding structures of these new inhibitors with mPGES-1 provide …

Estimation Of Exposure Distribution Adjusting For Association Between Exposure Level And Detection Limit, Yuchen Yang, Brent J. Shelton, Thomas Tucker, Li Li, Richard Kryscio, Li Chen

Statistics Faculty Publications

In environmental exposure studies, it is common to observe a portion of exposure measurements to fall below experimentally determined detection limits (DLs). The reverse Kaplan–Meier estimator, which mimics the well‐known Kaplan–Meier estimator for right‐censored survival data with the scale reversed, has been recommended for estimating the exposure distribution for the data subject to DLs because it does not require any distributional assumption. However, the reverse Kaplan–Meier estimator requires the independence assumption between the exposure level and DL and can lead to biased results when this assumption is violated. We propose a kernel‐smoothed nonparametric estimator for the exposure distribution without imposing …

Cascaded Multi-View Canonical Correlation (Camcco) For Early Diagnosis Of Alzheimer's Disease Via Fusion Of Clinical, Imaging And Omic Features, Asha Singanamalli, Haibo Wang, Anant Madabhushi, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford Jack, William Jagust, John Trojanowki, Arthur Toga, Laurel Beckett, Robert Green, Andrew Saykin, John Morris, Leslie Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith Heidebrink, Charles Smith, Greg A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Neurology Faculty Publications

The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer's Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic …

Improving The Quality Of Bedside Shift Report Behavior: Implementing A Standardized Bedside Report Tool On The Medical-Surgical Floor At Woodland Healthcare, Amanda Waggoner

Master's Projects and Capstones

Abstract

Nursing handoff communication at change-of-shift is a frequent, yet highly essential nursing responsibility that lays the foundation for providing care that is safe and consistent (Grimshaw, Hatch, Willard, & Abraham, 2016). A microsystem assessment conducted on the medical-surgical unit at Woodland Healthcare (WHC) utilizing the 5P’s (Purpose, Patients, Professionals, Processes, Patterns) revealed that only 6% of twelve hour night shift nurses were performing a quality BSR and 40% of twelve hour day shift nurses reported feeling satisfied with shift report. Additionally, three reportable events occurred as a result communication related errors which led to increased spending on behalf of …

Sertraline And Phenytoin Drug Interaction In A Geriatric Patient, Kobi T. Nathan, Heather A. Hopkins, Stefanie E. Diloreto, Nhon A. Ta, Thomas V. Caprio

Pharmacy Faculty/Staff Publications

This report presents the case of a 78-year-old man residing in a nursing home who presented with a 2-month history of increasing lethargy and confusion. These symptoms coincided with the initiation of sertraline in the patient. Among other medications, he was also taking phenytoin. The medical team concluded that the cause of the patient’s lethargy and confusion was a drug interaction between sertraline and phenytoin. Phenytoin was held, while the sertraline was slowly tapered to discontinuation. The patient’s symptoms resolved soon thereafter. Future research is needed to better guide clinicians in appropriate selection, dosing, and monitoring of selective serotonin reuptake …

Gulf States Health Policy Center Community Research Fellows Birmingham, Al Evaluation Report, Candace Bright, Braden Bagley

Faculty Publications

The Gulf States Community Research Program (GSCRP) program took place in Birmingham between January 10th, 2017 and May 16th, 2017. This report reflects the implementation and evaluation of a community based participatory training (CBPR) program for this cohort of community members. The report provides data on the assessment of the program’s effectiveness in promoting the role of underserved populations in research by enhancing the capacity for CBPR. In assessing the social network development of the cohort, we seek to understand effectiveness in bridging many community roles to serve the purpose of addressing health disparities. Specifically, the report assesses if the …

August 2017, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Exploring The Role Of Nutrition Education In Reducing Obesity Among The U.S. Adult Population, Nikitha Reddy Ravula

Master's Projects and Capstones

Obesity is a major concern among the low-income groups, yet the problem lacks adequate awareness. It is observed that the prevalence of obesity in the United States is increasing in the U.S., this paper is focused on obtaining information on low-income participants’ knowledge about consumption of nutritious food and its contribution in preventing obesity. This paper focuses on identifying the steps that participants have been taking to prevent obesity. To reach the goal of this qualitative study two surveys were designed by the researcher. From the study, it was found that majority of the participants were aware that consumption of …

Reducing The Risk Of Hypothermia In Neonatal Infants, Monika Klett-Dunbar

Master's Projects and Capstones

Abstract

Global Aim: To improve infant thermoregulation within the first 24 hours of life of the high risk preterm and very low birth weight (VLBW) infant population in the NICU, thereby reducing rates of morbidity and mortality due to complications influenced by infant hypothermia. Project Aim: To reduce the rate of hypothermia at one hour and the first 24 hours of life in the target population of preterm neonates weighing less than 1500 grams with a gestational age less than 32 weeks from 9.5% to < 5% through the consistent use of a specific bundle of interventions applied in the labor and delivery setting, by December 2017. The aim of the current initiative is also to build on the success of the pilot program launched in 2015 by adding to the preliminary bundle of initiatives, and sustaining hard-won achievements by reinforcing education measures to the nursing and medical teams involved in the infant delivery and NICU admission process. Background: Hypothermia is a major factor in morbidity and mortality of low-birth-weight premature infants, …

Transcutaneous Electrical Nerve Stimulation (Tens) For Pain Management In Sickle Cell Disease, Sudipta Pal, Ruchita Dixit, Soe Moe, Myron A. Godinho, Adinegara B.L. Abas, Samir K. Ballas, Shanker Ram, Uduman A.M. Yousuf

Cardeza Foundation for Hematologic Research

No abstract provided.

Influence Of Socioeconomic Status On Event-Free Survival In Children Diagnosed With Acute Lymphoblastic Leukemia, Jordan L. Chester

Masters Theses

Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children. However, little is known about how socioeconomic status (SES) influences the outcomes of children diagnosed with ALL. The goal of the research study was to understand how SES impacted the outcomes of children diagnosed with ALL, with a particular interest in children living in West Michigan. Children ages 0-14 years who received treatment for ALL at Spectrum Health’s Helen DeVos Children’s Hospital’s Pediatric Hematology and Oncology program between the years 2002-2011 were considered for this study. Eligible participant’s zip codes and dates of relapse/death were obtained …

Prognostic Value Of Routine Laboratory Variables In Prediction Of Breast Cancer Recurrence., Zhu Zhu, Ling Li, Zhong Ye, Tong Fu, Ye Du, Aiping Shi, Di Wu, Ke Li, Yifan Zhu, Chun Wang, Zhimin Fan

Department of Medical Oncology Faculty Papers

The prognostic value of routine laboratory variables in breast cancer has been largely overlooked. Based on laboratory tests commonly performed in clinical practice, we aimed to develop a new model to predict disease free survival (DFS) after surgical removal of primary breast cancer. In a cohort of 1,596 breast cancer patients, we analyzed the associations of 33 laboratory variables with patient DFS. Based on 3 significant laboratory variables (hemoglobin, alkaline phosphatase, and international normalized ratio), together with important demographic and clinical variables, we developed a prognostic model, achieving the area under the curve of 0.79. We categorized patients into 3 …

Posttranscriptional Upregulation Of Idh1 By Hur Establishes A Powerful Survival Phenotype In Pancreatic Cancer Cells., Mahsa Zarei, Shruti Lal, Seth J. Parker, Avinoam Nevler, Ali Vaziri-Gohar, Katerina Dukleska, Nicole C. Mambelli-Lisboa, Cynthia Moffat, Fernando F Blanco, Saswati N. Chand, Masaya Jimbo, Joseph A. Cozzitorto, Wei Jiang, Charles J. Yeo, Eric R. Londin, Erin L. Seifert, Christian M. Metallo, Jonathan R. Brody, Jordan M. Winter

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C > 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal …

Implementation Of An Evidenced-Based Practice Curriculum To Improve Nursing Practice For Epidural Administration And Monitoring, Chatty O'Keeffe

Master's Projects and Capstones

Abstract

Epidural analgesia (EA) is one inpatient pain management option prescribed by Acute Pain Services (APS) at VA Puget Sound Health Care Services (VAPSHCS). Historically, EA nursing care at VAPSHCS has been managed by surgical units. However, in the last two years, facility restructuring and budget constraints have led to reorganization and consolidation of units. The reduction in units providing nursing EA care has resulted in an overflow of EA patients to the medical intensive care unit (MICU). A previous gap analysis of the compliance in nursing performance of EA nursing care on the surgical acute care unit demonstrated poor …

Midline Catheter Usage In The Neonatal Population, Kelly Freeland

Master's Projects and Capstones

Neonatal sepsis is associated with increased mortality and morbidities including lengthy hospital stays. Neonate’s immature immune system and susceptibility to sepsis make them prone to antibiotic treatment. Lack of recommendations points to the need for evidence-based practices when selecting a vascular access device (VAD). Literature reviewed demonstrated that a midline catheter (MC) was an option for a VAD with neonatal populations requiring antibiotic therapy more than 48 hours. MCs offer fewer complications compared to the peripheral intravenous (PIV) device. The objective of this project is to reduce the amount of pain experienced by neonates by reducing the number of PIV …

A Heuristic Inquiry: The Narrative Of A Beginning Dance/Movement Therapist's Professional Identity Development, Danielle Parmacek

Creative Arts Therapies Theses

There are theories, models, and theses that explain what generally happens as people move through the identified phases of counselor and professional identity development. However, there is little literature that illustrates how this growth actually happens for clinicians. The purpose of this heuristic self-study was to identify and gain a deeper understanding of the narrative of how my clinical experiences have influenced my professional identity as a dance/movement therapist. This study utilized the six phases of heuristic inquiry as a structure to guide this discovery. My personal recollections of three identified cases were used as data, which was then analyzed …

What's Happening: August 14, 2017, Maine Medical Center

What's Happening

No abstract provided.

Carotid Body-Mediated Chemoreflex Drive In The Setting Of Low And High Output Heart Failure., Rodrigo Del Rio, David C. Andrade, Camilo Toledo, Hugo S. Diaz, Claudia Lucero, Alexis Arce-Alvarez, Noah J. Marcus, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

Enhanced carotid body (CB) chemoreflex function is strongly related to cardiorespiratory disorders and disease progression in heart failure (HF). The mechanisms underlying CB sensitization during HF are not fully understood, however previous work indicates blood flow per se can affect CB function. Then, we hypothesized that the CB-mediated chemoreflex drive will be enhanced only in low output HF but not in high output HF. Myocardial infarcted rats and aorto-caval fistulated rats were used as a low output HF model (MI-CHF) and as a high output HF model (AV-CHF), respectively. Blood flow supply to the CB region was decreased only in …

Week Of August 14, 2017, New York Medical College

InTouch

• The School of Medicine Class of 2021 Joins the College Community
• Center for Long-Term Care Welcomes Notable Physiotherapist and Philanthropist for Special Presentation
• GSBMS Welcomes New Students
• HSL Hosts Talk on the Health of the First President

Integrative Analysis Identifies Four Molecular And Clinical Subsets In Uveal Melanoma., A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman

Articles, Abstracts, and Reports

Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.

Meta-Regression: Prognostic Models As Objective Predictors Of Mortality Among Icu Cancer Patients, Sheila Donnell

Nursing Theses and Dissertations

Cancer patients admitted to the intensive care unit (ICU) may be experiencing complications of disease or treatment-related effects. While acute complications related to disease and/or its therapeutic management vary in severity, the approach to ICU-centered care is complicated by actual versus perceived risks of poor outcomes. Prognostic models that inform clinical judgment of nurses and physicians may prove helpful in this population. The Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) are ICU-based models predicting 30-day mortality among the general ICU population. Although studies have been …

Gulf States Health Policy Center Community Research Fellows Mobile, Al Evaluation Report, Candace Bright, Braden Bagley

Faculty Publications

The Gulf States Community Research Program (GSCRP) program took place in Mobile between January 10th, 2017 and May 9, 2017. This report reflects the implementation and evaluation of a community based participatory training (CBPR) program for this cohort of community members. The report provides data on the assessment of the program’s effectiveness in promoting the role of underserved populations in research by enhancing the capacity for CBPR. In assessing the social network development of the cohort, we seek to understand effectiveness in bridging many community roles to serve the purpose of addressing health disparities. Specifically, the report assesses if the …

Clearing The Pathway To Chemotherapy Certification For Inpatient Nurses, Shari Lee Kellen Rn, Ocn, Onn

Master's Projects and Capstones

Abstract

A clinical nurse leader (CNL) project was conducted, in a medical-surgical oncology unit in a community-based hospital, to evaluate and improve upon the decreasing number of chemotherapy certified nurses. A Likert survey of the nurses provided a self-assessment of competency in handling chemotherapy patients, and perceived barriers to achieving chemotherapy certification. The surveys revealed that nurses felt fearful of exposure to hazardous medications, that chemotherapy assignments were too stressful, and that there was minimal chemotherapy competency amongst leadership. An education program was implemented, covering proper use of personal protective equipment (PPE) and safe handling, practicing resilience to mitigate stress, …

A Demonstration Project To Address Juvenile Drug Addiction, Mary Ellen Broaddus

Graduate Theses, Dissertations, and Capstones

The rise in adolescent drug use and addiction is becoming a worldwide phenomenon. An eleven year study of youth in European countries found drug use widespread and increasing (Molinaro, Sicilian, & Curzio, 2011). In 2013 there were over 2.8 million new users of illicit drugs, over half of whom were under 18 years of age (‘Drug Facts’, 2015).

Adolescents are at unique risk because biochemical distinctions in their brains, when compared with adults, prompt more risk-taking behaviors (Gallager, 2014). Health risks are considerable and include hypertension, stroke, convulsions and seizures, and liver disease such as cirrhosis and hepatitis. In 2013 …

Alternative Healthy Eating Index 2010, Dietary Inflammatory Index And Risk Of Mortality: Results From The Whitehall Ii Cohort Study And Meta-Analysis Of Previous Dietary Inflammatory Index And Mortality Studies, Nitin Shivappa, James R. Hébert, Mika Kivimaki, Tasnime Akbaraly

Faculty Publications

We aimed to examine the association between the Alternative Healthy Eating Index updated in 2010 (AHEI-2010), the Dietary Inflammatory Index (DIITM) and risk of mortality in the Whitehall II study. We also conducted a meta-analysis on the DII-based results from previous studies to summarise the overall evidence. Data on dietary behaviour assessed by self-administered repeated FFQ and on mortality status were available for 7627 participants from the Whitehall II cohort. Cox proportional hazards regression models were performed to assess the association between cumulative average of AHEI-2010 and DII scores and mortality risk. During 22 years of follow-up, 1001 participants died …

Mentor Program, Nicole Van Aken

Master's Projects and Capstones

Stanford Health Care- Valley Medical Oncology Consultants (SHC-VMOC) treats patients diagnosed with cancer or hematology disorders at multiple doctor’s offices and infusion centers across the Bay Area. Presently all five locations with nurses employed in the infusion centers are understaffed. The mentor program was created to train nurses to become mentors. Additional to train new hires and foster relationships between new hires and established nurses while investing in each individual. The clinical nurse leader theme that is being addressed is organizational and system leadership. The first step to implementing the program was to talk to management about the additional cost …

Improving Stress Echocardiogram Access For Patients With Low-Risk Chest Pain In The Emergency Department Clinical Decision Unit, Rosalie Geronimo

Master's Projects and Capstones

This paper attempts to demonstrate improved stress echocardiogram scheduling access for patients with low-risk chest pain in the Emergency Department Clinical Decision Unit.