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David T Huang, Derek C Angus, Marc Moss, B Taylor Thompson, Niall D Ferguson, Adit Ginde, Michelle Ng Gong, Stephanie Gundel, Douglas L Hayden, R Duncan Hite, Peter C Hou, Catherine L Hough, Theodore J Iwashyna, Kathleen D Liu, Daniel S Talmor, Donald M Yealy
The Reevaluation Of Systemic Early neuromuscular blockade trial (ROSE) is a multicenter randomized trial designed to assess the efficacy and safety of early neuromuscular blockade in patients with moderate to severe acute respiratory distress syndrome. This document provides background for interpretation of the trial results, and highlights unique design approaches that may inform future trials of acute illness. We describe the process by which ROSE was chosen as the inaugural trial of the multidisciplinary Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, provide the trial methodology using the Consolidated Standards of Reporting Trials (CONSORT) framework, and discuss key design challenges and their resolution...
October 25, 2016: Annals of the American Thoracic Society
Diana Golden, Antonina Kolmakova, Sunitha Sura, Anthony T Vella, Ani Manichaikul, Xin-Qun Wang, Suzette J Bielinski, Kent D Taylor, Yii-Der Ida Chen, Stephen S Rich, Annabelle Rodriguez
BACKGROUND: The lipoprotein scavenger receptor BI (SCARB1) rs10846744 noncoding variant is significantly associated with atherosclerotic disease independently of traditional cardiovascular risk factors. We identified a potentially novel connection between rs10846744, the immune checkpoint inhibitor lymphocyte activation gene 3 (LAG3), and atherosclerosis. METHODS: In vitro approaches included flow cytometry, lipid raft isolation, phosphosignaling, cytokine measurements, and overexpressing and silencing LAG3 protein...
October 20, 2016: JCI Insight
Anne M Fitzpatrick, Daniel J Jackson, David T Mauger, Susan J Boehmer, Wanda Phipatanakul, William J Sheehan, James N Moy, Ian M Paul, Leonard B Bacharier, Michael D Cabana, Ronina Covar, Fernando Holguin, Robert F Lemanske, Fernando D Martinez, Jacqueline A Pongracic, Avraham Beigelman, Sachin N Baxi, Mindy Benson, Kathryn Blake, James F Chmiel, Cori L Daines, Michael O Daines, Jonathan M Gaffin, Deborah Ann Gentile, W Adam Gower, Elliot Israel, Harsha Vardhan Kumar, Jason E Lang, Stephen C Lazarus, John J Lima, Ngoc Ly, Jyothi Marbin, Wayne Morgan, Ross E Myers, J Tod Olin, Stephen P Peters, Hengameh H Raissy, Rachel G Robison, Kristie Ross, Christine A Sorkness, Shannon M Thyne, Stanley J Szefler
BACKGROUND: Phenotypic presentations in young children with asthma are varied and may contribute to differential responses to asthma controller medications. METHODS: The Individualized Therapy for Asthma in Toddlers (INFANT) study was a multicenter, randomized, double-blind, double-dummy, clinical trial in children age 12-59 months (n=300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2-8 week run-in period followed by three crossover periods with daily inhaled corticosteroid (ICS), daily leukotriene receptor antagonist (LTRA), and as-needed ICS treatment co-administered with albuterol...
October 21, 2016: Journal of Allergy and Clinical Immunology
Mark Doyle, Gerald M Pohost, C Noel Bairey Merz, Leslee J Shaw, George Sopko, William J Rogers, Barry L Sharaf, Carl J Pepine, Diane V Thompson, Geetha Rayarao, Lindsey Tauxe, Sheryl F Kelsey, Robert W W Biederman
BACKGROUND: We introduce an algorithmic approach to optimize diagnostic and prognostic value of gated cardiac single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) modalities in women with suspected myocardial ischemia. The novel approach: bio-informatics assessment schema (BIAS) forms a mathematical model utilizing MPI data and cardiac metrics generated by one modality to predict the MPI status of another modality. The model identifies cardiac features that either enhance or mask the image-based evidence of ischemia...
October 2016: Cardiovascular Diagnosis and Therapy
Mars Stone, Donald Brambilla, Karla Murcia, Melanie Dimapasoc, Sherri Cyrus, Ritchard G Cable, Joseph E Kiss, Michael P Busch
BACKGROUND: Understanding the effect of delayed processing of whole blood on plasma ferritin will inform the feasibility of both routine ferritin testing in donors and clinical research study design. STUDY DESIGN AND METHODS: Whole blood tubes drawn from 16 donors were held at 4°C and centrifuged at 24-hour intervals to assess plasma ferritin concentration up to 5 days after draw. Intraindividual variation over time was measured in 21 healthy donors in blood samples collected weekly for 4 weeks and then at 12 weeks...
October 2016: Transfusion
Andrew R Osterburg, Rebecca L Nelson, Benyamin Z Yaniv, Rachel Foot, Walter R F Donica, Madison A Nashu, Huan Liu, Kathryn A Wikenheiser-Brokamp, Joel Moss, Nishant Gupta, Francis X McCormack, Michael T Borchers
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that leads to progressive cyst formation and accelerated loss of pulmonary function. Neoplastic smooth muscle cells from an unknown source metastasize to the lung and drive destructive remodeling. Given the role of NK cells in immune surveillance, we postulated that NK cell activating receptors and their cognate ligands are involved in LAM pathogenesis. We found that ligands for the NKG2D activating receptor UL-16 binding protein 2 (ULBP2) and ULBP3 are localized in cystic LAM lesions and pulmonary nodules...
October 6, 2016: JCI Insight
Beverly A Schaefer, Jonathan M Flanagan, Ofelia A Alvarez, Stephen C Nelson, Banu Aygun, Kerri A Nottage, Alex George, Carla W Roberts, Connie M Piccone, Thad A Howard, Barry R Davis, Russell E Ware
Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate...
2016: PloS One
Jane Scott, Wayne Wang
A new Trans NIH K12 Program in Emergency Care Research was funded in late July 2016 and is funded by the National Heart, Lung and Blood Institute (NHLBI), the National Institute of Mental Health (NIMH) and National Institute of Nursing Research (NINR). The new program seeks to widen the scientific domain of emergency care research to include mental health and nursing research. This article is protected by copyright. All rights reserved.
October 6, 2016: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
Emily Riehm Meier, Angeli Rampersad
Once a fatal disease of childhood, more than 95% of patients born today with sickle cell disease (SCD) in developed countries are expected to survive into adulthood, largely because of improvements in supportive and preventive care (newborn screening, penicillin prophylaxis, transcranial Doppler (TCD) screening). Hydroxyurea (HU) therapy, the only oral medication currently available to prevent SCD complications, has become more widespread over the past 20 years. The NHLBI recommends that HU be offered to all patients with HbSS beginning at nine months of age, and the recently published Abnormal TCD with Transfusions Changing to HU (TWiTCH) trial has shown HU as an acceptable alternative to transfusion therapy for patients at high risk of stroke...
October 5, 2016: Pediatric Research
Reza Shekarriz-Foumani, Faezeh Khodaie
CONTEXT: Breast cancer has been considered as one of the most common types of cancer among the women worldwide, and patients with breast neoplasms have been reported with high prevalence of low serum 25-hydroxyvitamin D levels. OBJECTIVES: Our aim was to evaluate the correlation of plasma 25-hydroxyvitamin D deficiency with breast neoplasms risk among women. DATA SOURCES: PubMed database was searched with MeSH (medical subject headings) keywords "vitamin D AND breast neoplasms" which was restricted by original articles written only in English and published from January 1, 2014...
June 2016: Iranian Journal of Cancer Prevention
Drew E Carlson, Wayne C Wang, Jane D Scott
No abstract text is available yet for this article.
September 30, 2016: Circulation Research
Peng Wei, Ying Cao, Yiwei Zhang, Zhiyuan Xu, Il-Youp Kwak, Eric Boerwinkle, Wei Pan
With the advance of sequencing technologies, it has become a routine practice to test for association between a quantitative trait and a set of rare variants (RVs). While a number of RV association tests have been proposed, there is a dearth of study on the robustness of RV association testing for non-normal distributed traits, e.g., due to skewness, which is ubiquitous in cohort studies. By extensive simulations, we demonstrate that commonly used RV tests, including SKAT and SKAT-O, are not robust to heavy-tailed or right-skewed trait distributions with inflated type I error rates; in contrast, the adaptive sum of powered score (aSPU) test is much more robust...
September 27, 2016: G3: Genes—Genomes—Genetics
Paul L Auer, Alex P Reiner, Gao Wang, Hyun Min Kang, Goncalo R Abecasis, David Altshuler, Michael J Bamshad, Deborah A Nickerson, Russell P Tracy, Stephen S Rich, Suzanne M Leal
Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare variants in complex traits and to advance the goals of precision medicine. The technological and computing advances that have enabled us to generate WGS data on thousands of individuals have also outpaced our ability to perform analyses in scientifically and statistically rigorous and thoughtful ways. The past several years have witnessed the application of whole-exome sequencing (WES) to complex traits and diseases...
October 6, 2016: American Journal of Human Genetics
Roxana Daneshjou, Larisa H Cavallari, Peter E Weeke, Konrad J Karczewski, Katarzyna Drozda, Minoli A Perera, Julie A Johnson, Teri E Klein, Carlos D Bustamante, Dan M Roden, Christian Shaffer, Joshua C Denny, James L Zehnder, Russ B Altman
INTRODUCTION: African Americans have a higher incidence of venous thromboembolism (VTE) than European descent individuals. However, the typical genetic risk factors in populations of European descent are nearly absent in African Americans, and population-specific genetic factors influencing the higher VTE rate are not well characterized. METHODS: We performed a candidate gene analysis on an exome-sequenced African American family with recurrent VTE and identified a variant in Protein S (PROS1) V510M (rs138925964)...
September 2016: Molecular Genetics & Genomic Medicine
Amélie Pinard, David Salgado, Jean-Pierre Desvignes, Ghadi Rai, Nadine Hanna, Pauline Arnaud, Céline Guien, Maria Martinez, Laurence Faivre, Guillaume Jondeau, Catherine Boileau, Stéphane Zaffran, Christophe Béroud, Gwenaëlle Collod-Béroud
High-throughput next-generation sequencing such as whole-exome and whole-genome sequencing are being rapidly integrated into clinical practice. The use of these techniques leads to the identification of secondary variants for which decisions about the reporting or not to the patient need to be made. The American College of Medical Genetics and Genomics recently published recommendations for the reporting of these variants in clinical practice for 56 "actionable" genes. Among these, seven are involved in Marfan Syndrome And Related Disorders (MSARD) resulting from mutations of the FBN1, TGFBR1 and 2, ACTA2, SMAD3, MYH11 and MYLK genes...
September 20, 2016: Human Mutation
Constance A Opoku, Edmund Nii Laryea Browne, Kathryn Spangenberg, Cheryl Moyer, David Kolbilla, Katherine J Gold
OBJECTIVE: This study assessed the perception of risk of cervical cancer and existence of risk factors for cervical cancer based on five known risk factors among women attending the Tamale Teaching Hospital in Tamale, Ghana. METHODS: A consecutive sample of 300 women was interviewed using a semi-structured questionnaire to inquire about risk factors and perception of risk of cervical cancer. Specific risk factors that were explored included early coitarche, multiple sexual partners, polygamous relationships, history of smoking, and having a current partner who had multiple sexual partners...
June 2016: Ghana Medical Journal
Siddharth K Prakash, Carolyn A Bondy, Cheryl L Maslen, Michael Silberbach, Angela E Lin, Laura Perrone, Giuseppe Limongelli, Hector I Michelena, Eduardo Bossone, Rodolfo Citro, Scott A Lemaire, Simon C Body, Dianna M Milewicz
Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13...
September 8, 2016: American Journal of Medical Genetics. Part A
Qian Chen, Yuan Zhang, Ding Ding, Dan Li, Min Xia, Xinrui Li, Yunou Yang, Qing Li, Gang Hu, Wenhua Ling
BACKGROUND: The metabolic syndrome (MetS) and its metabolic risk factors appear to promote the development of atherosclerotic cardiovascular disease. The aim of this study was to examine the association of MetS and its individual components with all-cause and cardiovascular mortality among patients with coronary heart disease (CHD). METHODS: We performed a prospective, hospital-based cohort among 3599 CHD patients in China. Cox proportional hazards regression models were used to estimate the association of MetS and its components at baseline with risk of mortality...
December 1, 2016: International Journal of Cardiology
Girum Mekonnen, Salim S Hayek, Puja K Mehta, Qunna Li, Ernestine Mahar, Liping Mou, Tanya S Kenkre, John W Petersen, Babak Azarbal, Bruce Samuels, R David Anderson, Tara Sedlak, Melody Zaya, Megha Agarwal, Afsaneh Haftbaradaran, Margo Minissian, Eileen Handberg, Carl J Pepine, Christopher R Cogle, C Noel Bairey Merz, Edmund K Waller, Arshed A Quyyumi
BACKGROUND AND AIMS: Ischemia stimulates a reparative response resulting in mobilization of circulating progenitor cells (CPCs). We hypothesized that women with chronic myocardial ischemia from coronary microvascular disease (CMD) will mobilize CPCs. METHODS: In 123 women with ischemic symptoms and signs but no obstructive coronary artery disease (CAD) enrolled in the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD), we measured coronary flow reserve (CFR) in response to intracoronary adenosine...
October 2016: Atherosclerosis
Steven A Lubitz, Jennifer A Brody, Nathan A Bihlmeyer, Carolina Roselli, Lu-Chen Weng, Ingrid E Christophersen, Alvaro Alonso, Eric Boerwinkle, Richard A Gibbs, Joshua C Bis, L Adrienne Cupples, Peter J Mohler, Deborah A Nickerson, Donna Muzny, Marco V Perez, Bruce M Psaty, Elsayed Z Soliman, Nona Sotoodehnia, Kathryn L Lunetta, Emelia J Benjamin, Susan R Heckbert, Dan E Arking, Patrick T Ellinor, Honghuang Lin
Atrial fibrillation (AF) is a morbid and heritable arrhythmia. Over 35 genes have been reported to underlie AF, most of which were described in small candidate gene association studies. Replication remains lacking for most, and therefore the contribution of coding variation to AF susceptibility remains poorly understood. We examined whole exome sequencing data in a large community-based sample of 1,734 individuals with and 9,423 without AF from the Framingham Heart Study, Cardiovascular Health Study, Atherosclerosis Risk in Communities Study, and NHLBI-GO Exome Sequencing Project and meta-analyzed the results...
September 2016: PLoS Genetics
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