Medicine and Health Sciences Commons^™

Evaluating Turnaround Times For Early Infant Diagnosis Samples In Kenya From 2011-2014: A Retrospective Analysis Of Hitsystem Program Data., Catherine Wexler, An-Lin Cheng, Brad Gautney, Sarah Finocchario-Kessler, Kathy Goggin, Samoel Khamadi, Hitsystem Team

Manuscripts, Articles, Book Chapters and Other Papers

Long turnaround times (TAT) for the processing and posting of results of infant HIV DNA PCR samples can hinder the success of early infant diagnosis (EID) programs. The HITSystem is an eHealth intervention that alerts staff when services are overdue or results are delayed. We conducted a retrospective analysis of 3669 HIV-exposed infants enrolled in 15 Kenya hospital EID programs and three laboratories using the HITSystem from 2011-2014. We assessed mean and median TAT from when a sample was: 1) obtained to when it was shipped to the laboratory, 2) shipped to when it was received at the laboratory, 3) …

Reply: Do We Need Individualized Therapeutic Strategies In High-Risk Patients Treated With Hypothermia?, Neeraj Shah Md, Rahul Chaudhary, Kathan Mehta, Vratika Agarwal, Jalaj Garg Md, Ronald S. Freudenberger Md, Larry E. Jacobs Md, David A. Cox Md, Karl B Kern, Nainesh C. Patel Md

Cardiology Division

No abstract provided.

Natural Compounds Targeting Major Cell Signaling Pathways: A Novel Paradigm For Osteosarcoma Therapy., Pablo Angulo, Gaurav Kaushik, Dharmalingam Subramaniam, Prasad Dandawate, Kathleen Neville, Katherine Chastain, Shrikant Anant

Manuscripts, Articles, Book Chapters and Other Papers

Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Despite an incidence of three cases per million annually, it accounts for an inordinate amount of morbidity and mortality. While the use of chemotherapy (cisplatin, doxorubicin, and methotrexate) in the last century initially resulted in marginal improvement in survival over surgery alone, survival has not improved further in the past four decades. Patients with metastatic osteosarcoma have an especially poor prognosis, with only 30% overall survival. Hence, there is a substantial need for new therapies. The inability to control the metastatic progression of this localized cancer stems …

Addendum Guidelines For The Prevention Of Peanut Allergy In The United States: Report Of The National Institute Of Allergy And Infectious Diseases–Sponsored Expert Panel, Alkis Togias, Susan F. Cooper, Maria L. Acebal, Amal Assa'ad, James R. Baker, Lisa A. Beck, Julie Block, Carol Byrd-Bredbenner, Edmond S. Chan, Lawrence F. Eichenfield, David M Fleischer, George J. Fuchs Iii, Glenn T. Furuta, Matthew J. Greenhawt, Ruchi S. Gupta, Michele Habich, Stacie M. Jones, Kari Keaton, Antonella Muraro, Marshall Plaut, Lanny J. Rosenwasser, Daniel Rotrosen, Hugh A. Sampson, Lynda C. Schneider, Scott H. Sicherer, Robert Sidbury, Jonathan Spergel, David R. Stukus, Carina Venter, Joshua A. Boyce

Pediatrics Faculty Publications

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.

Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy …

The Annual Burden Of Seasonal Influenza In The Us Veterans Affairs Population, Yinong Young-Xu, Robertus Van Aalst, Ellyn Russo, Jason K. H. Lee, Ayman Chit

Dartmouth Scholarship

Seasonal influenza epidemics have a substantial public health and economic burden in the United States (US). On average, over 200,000 people are hospitalized and an estimated 23,000 people die from respiratory and circulatory complications associated with seasonal influenza virus infections each year. Annual direct medical costs and indirect productivity costs across the US have been found to average respectively at $10.4 billion and $16.3 billion. The objective of this study was to estimate the economic impact of severe influenza-induced illness on the US Veterans Affairs population. The five-year study period included 2010 through 2014. Influenza-attributed outcomes were estimated with a …

Improving Adolescent Hpv Vaccination In A Randomized Controlled Cluster Trial Using The 4 Pillars™ Practice Transformation Program., Richard K. Zimmerman, Krissy K. Moehling, Chyongchiou J. Lin, Song Zhang, Jonathan M. Raviotta, Evelyn C. Reis, Sharon Humiston, Mary Patricia Nowalk

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Uptake of meningococcal vaccine (MCV) and tetanus, diphtheria and pertussis (Tdap) vaccine among adolescents has approached Healthy People 2020 goals, but human papillomavirus (HPV) vaccination has not. This study evaluated an intervention using the 4 Pillars™ Practice Transformation Program to increase HPV, MCV and Tdap uptake among adolescents in primary care practices.

METHODS: Practices with at least 50 patients 11-17years old with estimated vaccination rates less than national goals, were assigned to intervention (n=11) and control (n=11) groups in a randomized controlled cluster trial; 9 intervention and 11 control sites completed the study. The baseline and active study periods …

Caphosol For Prevention Of Oral Mucositis In Pediatric Myeloablative Haematopoietic Cell Transplantation., Nathaniel Treister, Michael Nieder, Christina Baggott, Ellen Olson, Lu Chen, Ha Dang, Mark Krailo, Amanda August, Lillian Sung

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The primary objective was to determine whether topically administered Caphosol, rinsed orally four times daily at the initiation of conditioning, reduces the duration of severe oral mucositis (OM) compared with placebo among children and adolescents undergoing haematopoietic cell transplantation (HCT).

METHODS: This was a Children's Oncology Group multicentre randomised double-blinded placebo-controlled clinical trial. Patients between the ages of 4 and 21 years who were scheduled to undergo myeloablative HCT for any indication were randomised to Caphosol or placebo saline rinses four times daily from initiation of conditioning through day +20. Subjects were assessed daily for OM using the World …

Increased Ros Production In Non-Polarized Mammary Epithelial Cells Induces Monocyte Infiltration In 3d Culture, Linzhang Li, Jie Chen, Gaofeng Xiong, Daret K. St. Clair, Wei Xu, Ren Xu

Markey Cancer Center Faculty Publications

Loss of epithelial cell polarity promotes cell invasion and cancer dissemination. Therefore, identification of factors that disrupt polarized acinar formation is crucial. Reactive oxygen species (ROS) drive cancer progression and promote inflammation. Here, we show that the non-polarized breast cancer cell line T4-2 generates significantly higher ROS levels than polarized S1 and T4R cells in three-dimensional (3D) culture, accompanied by induction of the nuclear factor κB (NF-κB) pathway and cytokine expression. Minimizing ROS in T4-2 cells with antioxidants reestablished basal polarity and inhibited cell proliferation. Introducing constitutively activated RAC1 disrupted cell polarity and increased ROS levels, indicating that RAC1 is …

State-Level Immunization Information Systems: Potential For Childhood Immunization Data Linkages., Jill E. Fuller, Emmanuel B. Walter Jr., Nancy Dole, Richard O'Hara, Amy H. Herring, Maureen S. Durkin, Bonny Specker, Betty Wey

Ethel Austin Martin Program Publications

Objectives Sources of immunization data include state registries or immunization information systems (IIS), medical records, and surveys. Little is known about the quality of these data sources or the feasibility of using IIS data for research. We assessed the feasibility of collecting immunization information for a national children's health study by accessing existing IIS data and comparing the completeness of these data against medical record abstractions (MRA) and parent report. Staff time needed to obtain IIS and MRA data was assessed. Methods We administered a questionnaire to state-level IIS representatives to ascertain availability and completeness of their data for research …

Training Us Health Care Professionals On Human Trafficking: Where Do We Go From Here?, Clydette Powell, Kirsten Dickins, Hanni Stoklosa

Pediatrics Faculty Publications

Some 21 million adults and children are labor-trafficked or sex-trafficked through force, fraud, or coercion. In recognition of the interface between trafficking victims and the healthcare setting, over the last 10 years there has been a notable increase in training of health care professionals (HCPs) on human trafficking (HT) and its health implications. Many organizations have developed curricula and offered training in various clinical settings. However, methods and content of this education on trafficking vary widely, and there is little evaluation of the impact of the training. The goal of this study was to assess the gaps and strengths in …

The Current Consensus On The Clinical Management Of Intracranial Ependymoma And Its Distinct Molecular Variants., Kristian W Pajtler, Stephen C Mack, Vijay Ramaswamy, Christian A Smith, Hendrik Witt, Amy Smith, Eugene Hwang, +Several Additional Authors

Pediatrics Faculty Publications

Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups. Discussion at the meeting generated a series of consensus statements and recommendations from the attendees, which comment on the prognostic evaluation and treatment decisions of patients …

Hypoactive Sexual Desire Disorder: International Society For The Study Of Women's Sexual Health (Isswsh) Expert Consensus Panel Review., Irwin Goldstein, Noel N Kim, Anita H Clayton, Leonard R Derogatis, Annamaria Giraldi, Sharon J Parish, James Pfaus, James A Simon, Sheryl A Kingsberg, Cindy Meston, Stephen M Stahl, Kim Wallen, Roisin Worsley

Obstetrics and Gynecology Faculty Publications

The objective of the International Society for the Study of Women's Sexual Health expert consensus panel was to develop a concise, clinically relevant, evidence-based review of the epidemiology, physiology, pathogenesis, diagnosis, and treatment of hypoactive sexual desire disorder (HSDD), a sexual dysfunction affecting approximately 10% of adult women. Etiologic factors include conditions or drugs that decrease brain dopamine, melanocortin, oxytocin, and norepinephrine levels and augment brain serotonin, endocannabinoid, prolactin, and opioid levels. Symptoms include lack or loss of motivation to participate in sexual activity due to absent or decreased spontaneous desire, sexual desire in response to erotic cues or stimulation, …

Conventional Early Infant Diagnosis In Lesotho From Specimen Collection To Results Usage To Manage Patients: Where Are The Bottlenecks?, Appolinaire Tiam, Michelle M Gill, Heather J Hoffman, Anthony Isavwa, Mafusi Mokone, Matokelo Foso, Jeffrey T Safrit, Lynne M Mofenson, Thorkild Tylleskär, Laura Guay

Epidemiology Faculty Publications

INTRODUCTION: Early infant diagnosis is an important step in identifying children infected with HIV during the perinatal period or in utero. Multiple factors contribute to delayed antiretroviral treatment initiation for HIV-infected children, including delays in the early infant HIV diagnosis cascade.

METHODS: We conducted a retrospective study to evaluate early infant diagnosis turnaround times in Lesotho. Trained staff reviewed records of HIV-exposed infants (aged-6-8 weeks) who received an HIV test during 2011. Study sites were drawn from Highlands, Foothills and Lowlands regions of Lesotho. Central laboratory database data were linked to facility and laboratory register information. Turnaround time geometric means …

Reliability And Validity Of The Hd-Pro-Triadtm, A Health-Related Quality Of Life Measure Designed To Assess The Symptom Triad Of Huntington's Disease., Nicholas R Boileau, Julie C Stout, Janes S Paulsen, David Cella, Michael K Mccormack, Martha A Nance, Samuel Frank, Jin-Shei Lai, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Huntington's disease (HD), is a neurodegenerative disorder that is associated with cognitive, behavioral, and motor impairments that diminish health related quality of life (HRQOL). The HD-PRO-TRIADTM is a quality of life measure that assesses health concerns specific to individuals with HD. Preliminary psychometric characterization was limited to a convenience sample of HD participants who completed measures at home so clinician-ratings were unavailable.

OBJECTIVES: The current study evaluates the reliability and validity of the HD-PRO-TRIADTM in a well-characterized sample of individuals with HD.

METHODS: Four-hundred and eighty-two individuals with HD (n = 192 prodromal, n = 193 early, and n …

Reduced Microrna-503 Expression Augments Lung Fibroblast Vegf Production In Chronic Obstructive Pulmonary Disease, Jun Ikari, Amy J. Nelson, Jannah Obaid, Alvaro Giron-Martinez, Kumiko Ikari, Fumihiko Makino, Shunichiro Iwasawa, Yoko Gunji, Maha Farid, Xingqi Wang, Hesham Basma, Dawn Demeo, Carol Feghali-Bostwick, Olaf Holz, Klaus Rabe, Xiangde Liu, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis. In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release. Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined. The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD. Primary adult lung fibroblasts were isolated from patients with or without COPD. MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without …

Delirium Update For Postacute Care And Long-Term Care Settings: A Narrative Review., Martin M Forsberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Advances have been made in our understanding of the neuropathogenesis, recognition, and strategies for reducing the incidence of delirium in acute-care settings. However, relatively little attention has been given to delirium in elderly patients in the postacute care (PAC) and long-term care (LTC) settings. The present article reviews the most relevant current research pertaining to this population. Hospital patients with delirium are often discharged to PAC settings. Delirium that develops in the LTC setting is often more insidious and subtle in presentation. Despite incorporating systematic screening tools for delirium in PAC and LTC settings, delirium prevention strategies have not yet …

Molecular Characterization Of Nrxn1 Deletions From 19,263 Clinical Microarray Cases Identifies Exons Important For Neurodevelopmental Disease Expression, Chelsea Lowther, Marsha Speevak, Christine M Armour, Elaine S Goh, Gail E Graham, Chumei Li, Susan Zeesman, Malgorzata J M Nowaczyk, Lee-Anne Schultz, Antonella Morra, Rob Nicolson, Peter Bikangaga, Dawa Samdup, Mostafa Zaazou, Kerry Boyd, Jack H Jung, Victoria Siu, Manjulata Rajguru, Sharan Goobie, Mark A Tarnopolsky, Chitra Prasad, Paul T Dick, Asmaa S Hussain, Margreet Walinga, Renske G Reijenga, Matthew Gazzellone, Anath C Lionel, Christian R Marshall, Stephen W Scherer, Dimitri J Stavropoulos, Elizabeth Mccready, Anne S Bassett

Paediatrics Publications

PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions.

METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions.

RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P < 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3' end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5' NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035).

CONCLUSIONS: The results support the importance of exons …

Brainstem Shape Is Affected By Clinical Course In The Neonatal Intensive Care Unit, Marcus Lo, Leire Zubiaurre-Elorza, Conor Wild, Annika C Linke, David S C Lee, Victor K Han, Rhodri Cusack

Paediatrics Publications

The brainstem, critical for motor function, autonomic regulation, and many neurocognitive functions, undergoes rapid development from the third trimester. Accordingly, we hypothesized it would be vulnerable to insult during this period, and that a difficult clinical course in the neonatal intensive care unit (NICU) would affect development, and be reflected through atypical shape. Our study population consisted of 66 neonates - all inpatients from the NICU at Victoria Hospital, London Health Sciences Centre, ON, Canada, of which 45 entered the final analysis. The cohort varied in gestational age (GA) and ranged from neurologically healthy to severely brain-injured. Structural MRI was …

Pediatric Emergency Care Capacity In A Low-Resource Setting: An Assessment Of District Hospitals In Rwanda, Celestin Hategeka, Jean Shoveller, Lisine Tuyisenge, Cynthia Kenyon, David F Cechetto, Larry D Lynd

Paediatrics Publications

BACKGROUND: Health system strengthening is crucial to improving infant and child health outcomes in low-resource countries. While the knowledge related to improving newborn and child survival has advanced remarkably over the past few decades, many healthcare systems in such settings remain unable to effectively deliver pediatric advance life support management. With the introduction of the Emergency Triage, Assessment and Treatment plus Admission care (ETAT+)-a locally adapted pediatric advanced life support management program-in Rwandan district hospitals, we undertook this study to assess the extent to which these hospitals are prepared to provide this pediatric advanced life support management. The results of …

Identification Of Epigenetic Signature Associated With Alpha Thalassemia/Mental Retardation X-Linked Syndrome, Laila C Schenkel, Kristin D Kernohan, Arran Mcbride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene

RESULTS: We performed genome-wide DNA methylation assessment of the peripheral blood samples from 18 patients with ATR-X and compared it to 210 controls. We demonstrated the evidence of a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of ATRX patients, which was corroborated by targeted bisulfite sequencing experiments. Although genomically represented, differentially methylated regions showed evidence of preferential clustering in pericentromeric and telometric chromosomal regions, areas where ATRX has multiple functions related to maintenance of heterochromatin and genomic integrity.

CONCLUSION: …

Desynchronization Of Autonomic Response And Central Autonomic Network Connectivity In Posttraumatic Stress Disorder, Janine Thome, Maria Densmore, Paul A Frewen, Margaret C Mckinnon, Jean Théberge, Andrew A Nicholson, Julian Koenig, Julian F Thayer, Ruth A Lanius

Department of Medicine Publications

OBJECTIVES: Although dysfunctional emotion regulatory capacities are increasingly recognized as contributing to posttraumatic stress disorder (PTSD), little work has sought to identify biological markers of this vulnerability. Heart rate variability (HRV) is a promising biomarker that, together with neuroimaging, may assist in gaining a deeper understanding of emotion dysregulation in PTSD. The objective of the present study was, therefore, to characterize autonomic response patterns, and their related neuronal patterns in individuals with PTSD at rest.

METHODS: PTSD patients (N = 57) and healthy controls (N = 41) underwent resting-state fMRI. Connectivity patterns of key regions within the central autonomic network …

Clinician's Commentary On Patterson Et Al., Sue Peters

Physical Therapy Publications

No abstract provided.

Sustained Nitric Oxide-Releasing Nanoparticles Interfere With Methicillin-Resistant Staphylococcus Aureus Adhesion And Biofilm Formation In A Rat Central Venous Catheter Model., Mircea Radu Mihu, Vitor Cabral, Rodney Pattabhi, Moses T Tar, Kelvin P Davies, Adam J Friedman, Luis R Martinez, Joshua D Nosanchuk

Dermatology Faculty Publications

Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial …

Variability In Objective And Subjective Measures Affects Baseline Values In Studies Of Patients With Copd, Wayne H. Anderson, Jae Wook Ha, David J. Couper, Wanda K. O'Neal, R. Graham Barr, Eugene R. Bleecker, Elizabeth E. Carretta, Christopher B. Cooper, Claire M. Doerschuk, M. Bradley Drummond, Meilan K. Han, Nadia N. Hansel, Victor Kim, Eric C. Kleerup, Fernando J. Martinez, Stephen I. Rennard, Donald Tashkin, Prescott G. Woodruff, Robert Paine, Jeffrey L. Curtis, Richard W. Kanner, Spiromics Research Group

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety.

OBJECTIVES: Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes.

METHODS: Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same …

Foxc1 Is Associated With Estrogen Receptor Alpha And Affects Sensitivity Of Tamoxifen Treatment In Breast Cancer., Jinhua Wang, Yali Xu, Li Li, Lin Wang, Ru Yao, Qiang Sun, Guanhua Du

Articles, Abstracts, and Reports

FOXC1 is a member of Forkhead box transcription factors that participates in embryonic development and tumorigenesis. Our previous study demonstrated that FOXC1 was highly expressed in triple-negative breast cancer. However, it remains unclear what is the relation between FOXC1 and ERα and if FOXC1 regulates expression of ERα. To explore relation between FOXC1 and ERα and discover regulation of ERα expression by FOXC1 in breast cancer, we analyzed data assembled in the Oncomine and TCGA, and found that there was significantly higher FOXC1 expression in estrogen receptor-negative breast cancer than that in estrogen receptor-positive breast cancer. Overexpression of FOXC1 reduced …

Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough

Articles, Abstracts, and Reports

Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma. We demonstrate that STING ligands cause rapid regression of …

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …

Body Mass Index Change In Gastrointestinal Cancer And Chronic Obstructive Pulmonary Disease Is Associated With Dedicator Of Cytokinesis 1, Merry-Lynn Noelle Mcdonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.

METHODS: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years …

Reliability Of Medical Records In Diagnosing Inflammatory Breast Cancer In Egypt, Lynne Le, Catherine Schairer, Ahmed Hablas, Jane L. Meza, Shinobu Watanabe-Galloway, Mohamed Ramadan, Sofia D. Merajver, Ibrahim A. Seifeldin, Amr S. Soliman

Journal Articles: Epidemiology

BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive breast cancer diagnosed clinically by the presence of diffuse erythema, peau d'orange, and edema that arise quickly in the affected breast. This study evaluated the validity of medical records in Gharbiah, Egypt in identifying clinical signs/symptoms of IBC. For 34 IBC cases enrolled in a case-control study at the Gharbiah Cancer Society and Tanta Cancer Center, Egypt (2009-2010), we compared signs/symptoms of IBC noted in medical records to those recorded on a standardized form at the time of IBC diagnosis by clinicians participating in the case-control study. We calculated the sensitivity …

Bid-Induced Release Of Aif/Endog From Mitochondria Causes Apoptosis Of Macrophages During Infection With, Wei-Lin Hu, Hai-Yan Dong, Yang Li, David M. Ojcius, Shi-Jun Li, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL-caspase-8/3 pathway plays an important role in the survival and proliferation of the pathogen in hosts. Although, the release of mitochondrial apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in leptospire-infected macrophages has been described, the mechanisms linking caspase and mitochondrion-related host-cell apoptosis has not been determined. Here, we demonstrated that leptospire-infection induced apoptosis through mitochondrial damages in macrophages. Apoptosis was caused by the mitochondrial release and nuclear translocation of AIF and/or EndoG, leading to nuclear DNA fragmentation. However, the mitochondrion-related CytC-caspase-9/3 pathway was …