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https://www.readbyqxmd.com/read/29604160/baseline-characteristics-and-enrichment-results-of-the-study-of-diabetic-nephropathy-with-atrasentan-sonar-trial
#1
Hiddo J L Heerspink, Dennis L Andress, George Bakris, John J Brennan, Ricardo Correa-Rotter, Fan Fan Hou, Dalane W Kitzman, Donald Kohan, Hirofumi Makino, John McMurray, Vlado Perkovic, Sheldon Tobe, Melissa Wigderson, Tingting Yi, Hans-Henrik Parving, Dick de Zeeuw
INTRODUCTION: The SONAR trial uses an enrichment design based on the individual response to the selective endothelin receptor antagonist atrasentan on efficacy (the degree of the individual response in urinary albumin:creatinine ratio, UACR), and safety/tolerability (signs of sodium retention and acute increases in serum creatinine) to assess the effects of this agent on major renal outcomes. The patient population and enrichment results are described here. METHODS: Patients with type 2 diabetes with estimated Glomerular Filtration Rate (eGFR) between 25 and 75 ml/min/1...
March 31, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29572002/early-contrast-enhancement-a-novel-magnetic-resonance-imaging-biomarker-of-pleural-malignancy
#2
Selina Tsim, Catherine A Humphreys, Gordon W Cowell, David B Stobo, Colin Noble, Rosemary Woodward, Caroline A Kelly, Laura Alexander, John E Foster, Craig Dick, Kevin G Blyth
INTRODUCTION: Pleural Malignancy (PM) is often occult on subjective radiological assessment. We sought to define a novel, semi-objective Magnetic Resonance Imaging (MRI) biomarker of PM, targeted to increased tumour microvessel density (MVD) and applicable to minimal pleural thickening. MATERIALS AND METHODS: 60 consecutive patients with suspected PM underwent contrast-enhanced 3-T MRI then pleural biopsy. In 58/60, parietal pleura signal intensity (SI) was measured in multiple regions of interest (ROI) at multiple time-points, generating ROI SI/time curves and Mean SI gradient (MSIG: SI increment/time)...
April 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29567793/corneal-transplant-follow-up-study-ii-ctfs-ii-a-prospective-clinical-trial-to-determine-the-influence-of-hla-class-ii-matching-on-corneal-transplant-rejection-baseline-donor-and-recipient-characteristics
#3
W John Armitage, Helen L Winton, Mark N A Jones, Julie M Crewe, Chris A Rogers, Derek M Tole, Andrew D Dick
PURPOSE: To describe a study to determine the influence of HLA class II matching on allograft rejection of high-risk, full-thickness corneal transplants. METHODS: A prospective, longitudinal, clinical trial (ISRCTN25094892) with a primary outcome measure of time to first clinically determined rejection episode. Tissue typing used DNA-based techniques. Corneas were allocated to patients with ≤2 human leucocyte antigen (HLA) class I antigen mismatches by cohort minimisation to achieve 0, 1 or 2 HLA class II (HLA-DR) antigen mismatches...
March 22, 2018: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/29505775/autoimmunity-autoinflammation-and-infection-in-uveitis
#4
John V Forrester, Lucia Kuffova, Andrew D Dick
PURPOSE: To review the pathogenesis of uveitis in light of recent advances in our understanding of innate and adaptive immune responses and their regulation. DESIGN: A perspective. METHODS: The methods included a review of prevailing views on the pathogenesis of uveitis, and an analysis of developments in immunology which impact on its conceptual basis, particularly the concept of immunological tolerance and its loss in autoimmunity. Importantly, the role of infection in the pathogenesis of uveitis is evaluated...
March 2, 2018: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/29495257/a-fluorescent-cell-based-system-for-imaging-zika-virus-infection-in-real-time
#5
Michael J McFadden, Aaron Mitchell-Dick, Christine Vazquez, Allison E Roder, Kevin F Labagnara, John J McMahon, Debra L Silver, Stacy M Horner
Zika virus (ZIKV) is a re-emerging flavivirus that is transmitted to humans through the bite of an infected mosquito or through sexual contact with an infected partner. ZIKV infection during pregnancy has been associated with numerous fetal abnormalities, including prenatal lethality and microcephaly. However, until recent outbreaks in the Americas, ZIKV has been relatively understudied, and therefore the biology and pathogenesis of ZIKV infection remain incompletely understood. Better methods to study ZIKV infection in live cells could enhance our understanding of the biology of ZIKV and the mechanisms by which ZIKV contributes to fetal abnormalities...
February 24, 2018: Viruses
https://www.readbyqxmd.com/read/29409465/association-of-rs2282679-a-c-polymorphism-in-vitamin-d-binding-protein-gene-with-colorectal-cancer-risk-and-survival-effect-modification-by-dietary-vitamin-d-intake
#6
Yun Zhu, Peizhong Peter Wang, Guangju Zhai, Bharati Bapat, Sevtap Savas, Jennifer R Woodrow, Peter T Campbell, Yuming Li, Ning Yang, Xin Zhou, Elizabeth Dicks, John R Mclaughlin, Patrick S Parfrey
BACKGROUND: The rs2282679 A>C polymorphism in the vitamin D binding protein gene is associated with lower circulating levels of vitamin D. We investigated associations of this SNP with colorectal cancer (CRC) risk and survival and whether the associations vary by dietary vitamin D intake and tumor molecular phenotype. METHODS: A population-based case-control study identified 637 incident CRC cases (including 489 participants with follow-up data on mortality end-points) and 489 matched controls...
February 6, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29408959/a-comparative-analysis-of-phenotypic-predictors-of-mutations-in-familial-hypercholesterolemia
#7
Dick C Chan, Jing Pang, Amanda J Hooper, Damon A Bell, Timothy R Bates, John R Burnett, Gerald F Watts
Context: The gold standard for diagnosing familial hypercholesterolemia (FH) is identification of a causative pathogenic mutation. However, genetic testing is expensive and not widely available. Objective: To compare the validity of the Dutch Lipid Clinic Network (DLCN), Simon Broome (SB), Make Early Diagnosis to Prevent Early Deaths (MEDPED) and American Heart Association (AHA) criteria in predicting an FH-causing mutation. Design, Setting, and Patients: An adult cohort of unrelated patients referred to a lipid clinic for genetic testing...
February 2, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29408229/trends-in-care-processes-and-survival-following-prehospital-resuscitation-improvement-initiatives-for-out-of-hospital-cardiac-arrest-in-british-columbia-2006-2016
#8
Brian Grunau, Takahisa Kawano, William Dick, Ronald Straight, Helen Connolley, Robert Schlamp, Frank Scheuermeyer, Christopher B Fordyce, David Barbic, John Tallon, Jim Christenson
BACKGROUND: British Columbia (BC) Emergency Health Services implemented a strategy to improve outcomes for out-of-hospital cardiac arrest (OHCA), focusing on paramedic-led high-quality on-scene resuscitation. We measured changes in care metrics and survival trends. METHODS: This was a post-hoc study of prospectively identified consecutive non-traumatic ambulance-treated adult OHCAs from 2006 to 2016 within BC's four metropolitan areas. The primary outcome was survival to hospital discharge; we described available favourable neurological outcomes (mRS ≤3)...
February 2, 2018: Resuscitation
https://www.readbyqxmd.com/read/29405626/rationale-and-protocol-of-the-study-of-diabetic-nephropathy-with-atrasentan-sonar-trial-a-clinical-trial-design-novel-to-diabetic-nephropathy
#9
Hiddo J L Heerspink, Dennis L Andress, George Bakris, John J Brennan, Ricardo Correa-Rotter, Jyotirmoy Dey, Fan Fan Hou, Dalane W Kitzman, Donald Kohan, Hirofumi Makino, John McMurray, Vlado Perkovic, Sheldon Tobe, Melissa Wigderson, Hans-Henrik Parving, Dick de Zeeuw
AIMS: Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin-to-creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit...
February 6, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29405378/polygenic-risk-score-prediction-of-alcohol-dependence-symptoms-across-population-based-and-clinically-ascertained-samples
#10
Jeanne E Savage, Jessica E Salvatore, Fazil Aliev, Alexis C Edwards, Matthew Hickman, Kenneth S Kendler, John Macleod, Antti Latvala, Anu Loukola, Jaakko Kaprio, Richard J Rose, Grace Chan, Victor Hesselbrock, Bradley T Webb, Amy Adkins, Tim B Bigdeli, Brien P Riley, Danielle M Dick
BACKGROUND: Despite consistent evidence of the heritability of alcohol use disorders (AUDs), few specific genes with an etiological role have been identified. It is likely that AUDs are highly polygenic; however, the etiological pathways and genetic variants involved may differ between populations. The aim of this study was thus to evaluate whether aggregate genetic risk for AUDs differed between clinically ascertained and population-based epidemiological samples. METHODS: Four independent samples were obtained: 2 from unselected birth cohorts (Avon Longitudinal Study of Parents and Children [ALSPAC], N = 4,304; FinnTwin12 [FT12], N = 1,135) and 2 from families densely affected with AUDs, identified from treatment-seeking patients (Collaborative Study on the Genetics of Alcoholism, N = 2,097; Irish Affected Sib Pair Study of Alcohol Dependence, N = 706)...
February 5, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29389750/18f-florbetapir-positron-emission-tomography-determined-cerebral-%C3%AE-amyloid-deposition-and-neurocognitive-performance-after-cardiac-surgery
#11
Rebecca Y Klinger, Olga G James, Salvador Borges-Neto, Tiffany Bisanar, Yi-Ju Li, Wenjing Qi, Miles Berger, Niccolò Terrando, Mark F Newman, P Murali Doraiswamy, Joseph P Mathew
BACKGROUND: Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively. METHODS: Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9)...
April 2018: Anesthesiology
https://www.readbyqxmd.com/read/29386293/conserved-surface-residues-on-the-feline-calicivirus-fcv-capsid-are-essential-for-interaction-with-its-receptor-feline-junctional-adhesion-molecule-a-fjam-a
#12
Zhengchun Lu, Emily D Ledgerwood, Meleana M Hinchman, Robert Dick, John S L Parker
Host cell surface receptors are required for attachment, binding, entry and infection by nonenveloped viruses. Receptor binding can induce conformational changes in the viral capsid and/or the receptor that couple binding with downstream events in the viral life cycle (intracellular signaling, endocytosis and trafficking, and membrane penetration). Virus-receptor interactions also influence viral spread and pathogenicity. The interaction between feline calicivirus (FCV) and its receptor feline Junctional Adhesion Molecule A (fJAM-A) on host cells is required for infection and induces irreversible, inactivating conformational changes in the capsid of some viral strains...
January 31, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29363349/drug-metabolism-in-early-infancy-opioids-as-an-illustration
#13
Tamara van Donge, Paola Mian, Dick Tibboel, John van den Anker, Karel Allegaert
Drug dosing in infants frequently depends on body weight as a crude indicator for maturation. Fentanyl (metabolized by Cytochrome P450 3A4) and morphine (glucuronidated by UDP-glucuronosyltransferase-2B7) served as model drugs to provide insight in maturation patterns of these enzymes and provide understanding of the impact of non-maturational factors to optimize dosing in infants. Areas covered: Systematic searches on metabolism and population pharmacokinetic (Pop-PK) models for fentanyl and morphine were performed...
January 24, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29357720/severity-of-asphyxia-is-a-covariate-of-phenobarbital-clearance-in-newborns-undergoing-hypothermia
#14
Pavla Pokorná, Lenka Posch, Martin Šíma, Petr Klement, Ondrej Slanar, John van den Anker, Dick Tibboel, Karel Allegaert
AIM: Phenobarbital (PB) pharmacokinetics (PK) in asphyxiated newborns show large variability, not only explained by hypothermia (HT). We evaluated potential relevant covariates of PK of PB in newborns treated with or without HT for hypoxic-ischemic encephalopathy (HIE). METHODS: Clearance (CL), distribution volume (Vd) and elimination half-life (t1/2 ) were calculated using one-compartment analysis. Covariates were clinical characteristics (weight, gestational age, hepatic, renal, and circulatory status), comedication and HIE severity [time to reach normal aEEG pattern (Tnorm aEEG), dichotomous, within 24 h] and asphyxia severity [severe aspyhxia = pH ≤7...
February 5, 2018: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29342133/a-myc-enhancer-cluster-regulates-normal-and-leukaemic-haematopoietic-stem-cell-hierarchies
#15
Carsten Bahr, Lisa von Paleske, Veli V Uslu, Silvia Remeseiro, Naoya Takayama, Stanley W Ng, Alex Murison, Katja Langenfeld, Massimo Petretich, Roberta Scognamiglio, Petra Zeisberger, Amelie S Benk, Ido Amit, Peter W Zandstra, Mathieu Lupien, John E Dick, Andreas Trumpp, François Spitz
The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies. Here we show that an evolutionarily conserved region located 1.7 megabases downstream of the Myc gene that has previously been labelled as a 'super-enhancer' is essential for the regulation of Myc expression levels in both normal haematopoietic and leukaemic stem cell hierarchies in mice and humans. Deletion of this region in mice leads to a complete loss of Myc expression in haematopoietic stem cells and progenitors...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29334375/a-small-molecule-inhibitor-of-the-ubiquitin-activating-enzyme-for-cancer-treatment
#16
Marc L Hyer, Michael A Milhollen, Jeff Ciavarri, Paul Fleming, Tary Traore, Darshan Sappal, Jessica Huck, Judy Shi, James Gavin, Jim Brownell, Yu Yang, Bradley Stringer, Robert Griffin, Frank Bruzzese, Teresa Soucy, Jennifer Duffy, Claudia Rabino, Jessica Riceberg, Kara Hoar, Anya Lublinsky, Saurabh Menon, Michael Sintchak, Nancy Bump, Sai M Pulukuri, Steve Langston, Stephen Tirrell, Mike Kuranda, Petter Veiby, John Newcomb, Ping Li, Jing Tao Wu, Josh Powe, Lawrence R Dick, Paul Greenspan, Katherine Galvin, Mark Manfredi, Chris Claiborne, Benjamin S Amidon, Neil F Bence
The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade...
February 2018: Nature Medicine
https://www.readbyqxmd.com/read/29333336/medical-school-hotline-school-of-medicine-departments-year-in-review-2017-part-1
#17
Marla Berry, John Chen, Alan Hixon, Mariana Gerschenson, Nicholas James, David Jameson, Henry L Lew, Scott Lozanoff, Robert Nichols, Steven Seifried, Dick Teshima, Kamal Masaki, Elizabeth Tam, Barbara Ward, Steve Ward
No abstract text is available yet for this article.
January 2018: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/29280775/mental-health-in-the-workplace-a-call-to-action-proceedings-from-the-mental-health-in-the-workplace-public-health-summit
#18
Ron Z Goetzel, Enid Chung Roemer, Calliope Holingue, M Daniele Fallin, Katherine McCleary, William Eaton, Jacqueline Agnew, Francisca Azocar, David Ballard, John Bartlett, Michael Braga, Heidi Conway, K Andrew Crighton, Richard Frank, Kim Jinnett, Debra Keller-Greene, Sara Martin Rauch, Richard Safeer, Dick Saporito, Anita Schill, David Shern, Victor Strecher, Peter Wald, Philip Wang, C Richard Mattingly
OBJECTIVE: To declare a call to action to improve mental health in the workplace. METHODS: We convened a public health summit and assembled an Advisory Council consisting of experts in the field of occupational health and safety, workplace wellness, and public policy to offer recommendations for action steps to improve health and well-being of workers. RESULTS: The Advisory Council narrowed the list of ideas to four priority projects. CONCLUSIONS: The recommendations for action include developing a Mental Health in the Workplace 1) "How to" Guide, 2) Scorecard, 3) Recognition Program, and 4) Executive Training...
December 26, 2017: Journal of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/29273806/multiancestry-association-study-identifies-new-asthma-risk-loci-that-colocalize-with-immune-cell-enhancer-marks
#19
Florence Demenais, Patricia Margaritte-Jeannin, Kathleen C Barnes, William O C Cookson, Janine Altmüller, Wei Ang, R Graham Barr, Terri H Beaty, Allan B Becker, John Beilby, Hans Bisgaard, Unnur Steina Bjornsdottir, Eugene Bleecker, Klaus Bønnelykke, Dorret I Boomsma, Emmanuelle Bouzigon, Christopher E Brightling, Myriam Brossard, Guy G Brusselle, Esteban Burchard, Kristin M Burkart, Andrew Bush, Moira Chan-Yeung, Kian Fan Chung, Alexessander Couto Alves, John A Curtin, Adnan Custovic, Denise Daley, Johan C de Jongste, Blanca E Del-Rio-Navarro, Kathleen M Donohue, Liesbeth Duijts, Celeste Eng, Johan G Eriksson, Martin Farrall, Yuliya Fedorova, Bjarke Feenstra, Manuel A Ferreira, Maxim B Freidin, Zofia Gajdos, Jim Gauderman, Ulrike Gehring, Frank Geller, Jon Genuneit, Sina A Gharib, Frank Gilliland, Raquel Granell, Penelope E Graves, Daniel F Gudbjartsson, Tari Haahtela, Susan R Heckbert, Dick Heederik, Joachim Heinrich, Markku Heliövaara, John Henderson, Blanca E Himes, Hiroshi Hirose, Joel N Hirschhorn, Albert Hofman, Patrick Holt, Jouke Hottenga, Thomas J Hudson, Jennie Hui, Medea Imboden, Vladimir Ivanov, Vincent W V Jaddoe, Alan James, Christer Janson, Marjo-Riitta Jarvelin, Deborah Jarvis, Graham Jones, Ingileif Jonsdottir, Pekka Jousilahti, Michael Kabesch, Mika Kähönen, David B Kantor, Alexandra S Karunas, Elza Khusnutdinova, Gerard H Koppelman, Anita L Kozyrskyj, Eskil Kreiner, Michiaki Kubo, Rajesh Kumar, Ashish Kumar, Mikko Kuokkanen, Lies Lahousse, Tarja Laitinen, Catherine Laprise, Mark Lathrop, Susanne Lau, Young-Ae Lee, Terho Lehtimäki, Sébastien Letort, Albert M Levin, Guo Li, Liming Liang, Laura R Loehr, Stephanie J London, Daan W Loth, Ani Manichaikul, Ingo Marenholz, Fernando J Martinez, Melanie C Matheson, Rasika A Mathias, Kenji Matsumoto, Hamdi Mbarek, Wendy L McArdle, Mads Melbye, Erik Melén, Deborah Meyers, Sven Michel, Hamida Mohamdi, Arthur W Musk, Rachel A Myers, Maartje A E Nieuwenhuis, Emiko Noguchi, George T O'Connor, Ludmila M Ogorodova, Cameron D Palmer, Aarno Palotie, Julie E Park, Craig E Pennell, Göran Pershagen, Alexey Polonikov, Dirkje S Postma, Nicole Probst-Hensch, Valery P Puzyrev, Benjamin A Raby, Olli T Raitakari, Adaikalavan Ramasamy, Stephen S Rich, Colin F Robertson, Isabelle Romieu, Muhammad T Salam, Veikko Salomaa, Vivi Schlünssen, Robert Scott, Polina A Selivanova, Torben Sigsgaard, Angela Simpson, Valérie Siroux, Lewis J Smith, Maria Solodilova, Marie Standl, Kari Stefansson, David P Strachan, Bruno H Stricker, Atsushi Takahashi, Philip J Thompson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Carla M T Tiesler, Dara G Torgerson, Tatsuhiko Tsunoda, André G Uitterlinden, Ralf J P van der Valk, Amaury Vaysse, Sailaja Vedantam, Andrea von Berg, Erika von Mutius, Judith M Vonk, Johannes Waage, Nick J Wareham, Scott T Weiss, Wendy B White, Magnus Wickman, Elisabeth Widén, Gonneke Willemsen, L Keoki Williams, Inge M Wouters, James J Yang, Jing Hua Zhao, Miriam F Moffatt, Carole Ober, Dan L Nicolae
We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases...
January 2018: Nature Genetics
https://www.readbyqxmd.com/read/29245024/early-onset-tobacco-use-and-suicide-related-behavior-a-prospective-study-from-adolescence-to-young-adulthood
#20
Tellervo Korhonen, Elina Sihvola, Antti Latvala, Danielle M Dick, Lea Pulkkinen, John Nurnberger, Richard J Rose, Jaakko Kaprio
BACKGROUND: Developmental relationships between tobacco use and suicide-related behaviors (SRB) remain unclear. Our objective was to investigate the longitudinal associations of tobacco use in adolescence and SRB in adulthood. METHODS: Using a prospective design, we examined whether tobacco use in adolescence is associated with SRB (intentional self-injury, suicide ideation) in young adulthood in a population-based sample of 1330 twins (626 males, 704 females). The baseline and follow-up data were collected by professionally administered semi-structured poly-diagnostic interviews at ages 14 and 22, respectively...
April 2018: Addictive Behaviors
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