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https://www.readbyqxmd.com/read/29334375/a-small-molecule-inhibitor-of-the-ubiquitin-activating-enzyme-for-cancer-treatment
#1
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...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29334289/the-extracellular-matrix-degrading-protein-adamts5-is-expressed-in-the-nuclei-of-urothelial-cells-in-healthy-rats
#2
Dick Delbro, Lena Hallsberg, Ralph Peeker, Nikolai Scherbak, Magnus Fall, Rebecka Arnsrud Godtman
OBJECTIVE: The aim of this study was to investigate whether protein expression of the extracellular matrix-degrading protease ADAMTS5 can be demonstrated in the urinary bladder of healthy rats, and, if so, to determine the localization of this enzyme. MATERIALS AND METHODS: The experiments were conducted with eight inbred male Sprague-Dawley rats. Immunohistochemistry was used to investigate the expression of ADAMTS5 in the urinary bladder. Negative controls were established by either excluding the primary antibody or applying the antibody after it had been preabsorbed with its immunogenic peptide...
January 15, 2018: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/29333336/medical-school-hotline-school-of-medicine-departments-year-in-review-2017-part-1
#3
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/29332689/corrigendum-to-pesticides-drive-risk-in-wastewater-impacted-streams-during-low-flow-conditions-water-res-110-2017-366-377
#4
Nicole A Munz, Francis J Burdon, Dick de Zwart, Marion Junghans, Laura Melo, Marta Reyes, Urs Schönenberger, Heinz P Singer, Barbara Spycher, Juliane Hollender, Christian Stamm
No abstract text is available yet for this article.
February 1, 2018: Water Research
https://www.readbyqxmd.com/read/29332519/integrating-reproductive-health-services-into-intimate-partner-and-sexual-violence-victim-service-programs
#5
Theresa Gmelin, Claire A Raible, Rebecca Dick, Surabhi Kukke, Elizabeth Miller
This study assessed the feasibility of integrating reproductive health services into intimate partner violence/sexual violence (IPV/SV) programs. After a training for victim service agencies on integration of health services, we conducted semistructured interviews with IPV/SV program leadership. Leadership reported advocates were more likely to recognize the need to refer clients to health services, and revealed challenges operationalizing partnerships with health care centers. Training to integrate basic health assessment into victim services may be one way to address women's urgent health needs...
December 1, 2017: Violence Against Women
https://www.readbyqxmd.com/read/29330546/older-mothers-and-increased-impact-of-prenatal-screening-stable-livebirth-prevalence-of-trisomy-21-in-the-netherlands-for-the-period-2000-2013
#6
Maurike D de Groot-van der Mooren, Saskia Tamminga, Dick Oepkes, Michel E Weijerman, Martina C Cornel
In the Netherlands, there is no registry system regarding the livebirth prevalence of trisomy 21 (T21). In 2007, a national screening programme was introduced for all pregnant women, which may have changed the livebirth prevalence of T21. The aim of this study is to analyse trends in factors that influence livebirth prevalence of T21 and to estimate the livebirth prevalence of T21 for the period of 2000-2013. National data sets were used on the following: (1) livebirths according to maternal age and (2) prenatal testing and termination of pregnancy (ToP) following diagnosis of T21...
January 12, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29330299/effects-of-allelic-variations-in-the-human-myxovirus-resistance-protein-a-on-its-antiviral-activity
#7
Laura Graf, Alexej Dick, Franziska Sendker, Emanuel Barth, Manja Marz, Oliver Daumke, Georg Kochs
Only a minority of patients infected with seasonal influenza A viruses exhibits a severe or fatal outcome of infection, but the reasons for this inter-individual variability in influenza susceptibility are unclear. To gain further insights into the molecular mechanisms underlying this variability, we investigated naturally occurring allelic variations of the myxovirus resistance 1 (MX1) gene coding for the influenza restriction factor MxA. The interferon-induced dynamin-like GTPase consists of an N-terminal GTPase domain, a bundle signaling element, and a C-terminal stalk responsible for oligomerization and viral target recognition...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29329324/variability-and-cost-implications-of-three-generations-of-the-roche-lightcycler%C3%A2-480
#8
Maria Dullaert-de Boer, Onno W Akkerman, Marloes Vermeer, Dorine L J Hess, Huib A M Kerstjens, Richard M Anthony, Tjip S van der Werf, Dick van Soolingen, Adri G M van der Zanden
Real time PCR has become a dominant method for the highly sensitive detection of pathogens in clinical material. Real time PCR can generate a fluorescence signal by using fluorescence labelled probes, allowing us to detect and semi quantify the amount of amplified DNA. Here we test the variability of the detection system and cost implications of three different versions of the LightCycler® 480 (LC480), focusing on the intensity of fluorescence and Cq in monoplex and multiplex rtPCRs. For gastro-intestinal pathogens there was no correlation between the intensity of fluorescence and the Cq value in the different LC480 types...
2018: PloS One
https://www.readbyqxmd.com/read/29329163/the-importance-of-parental-connectedness-and-relationships-with-healthcare-professionals-in-end-of-life-care-in-the-picu
#9
Jeannette L Falkenburg, Dick Tibboel, Ruard R Ganzevoort, Saskia J Gischler, Monique van Dijk
OBJECTIVES: Support from healthcare professionals in a PICU is highly valuable for parents of dying children. The way they care for the patients and their families affects the parents' initial mourning process. This study explores what interaction with hospital staff is meaningful to parents in existential distress when their child is dying in the PICU. DESIGN: Qualitative interview study. SETTING: Level 3 PICU in the Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, and the Netherlands...
January 11, 2018: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/29329101/spatial-variation-of-endotoxin-concentrations-measured-in-ambient-pm10-in-a-livestock-dense-area-implementation-of-a-land-use-regression-approach
#10
Myrna M T de Rooij, Dick J J Heederik, Erik J H M van Nunen, Isabella J van Schothorst, Catharina B M Maassen, Gerard Hoek, Inge M Wouters
BACKGROUND: Results from studies on residential health effects of livestock farming are inconsistent, potentially due to simple exposure proxies used (e.g., livestock density). Accuracy of these proxies compared with measured exposure concentrations is unknown. OBJECTIVES: We aimed to assess spatial variation of endotoxin in PM10 (particulate matter ≤10μm) at residential level in a livestock-dense area, compare simple livestock exposure proxies to measured endotoxin concentrations, and evaluate whether land-use regression (LUR) can be used to explain spatial variation of endotoxin...
January 11, 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29326013/a-cluster-of-multidrug-resistant-mycobacterium-tuberculosis-among-patients-arriving-in-europe-from-the-horn-of-africa-a-molecular-epidemiological-study
#11
Timothy M Walker, Matthias Merker, Astrid M Knoblauch, Peter Helbling, Otto D Schoch, Marieke J van der Werf, Katharina Kranzer, Lena Fiebig, Stefan Kröger, Walter Haas, Harald Hoffmann, Alexander Indra, Adrian Egli, Daniela M Cirillo, Jérôme Robert, Thomas R Rogers, Ramona Groenheit, Anne T Mengshoel, Vanessa Mathys, Marjo Haanperä, Dick van Soolingen, Stefan Niemann, Erik C Böttger, Peter M Keller
BACKGROUND: The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan. METHODS: On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis...
January 8, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29325632/foreword
#12
EDITORIAL
Michael J Aminoff, François Boller, Dick F Swaab
No abstract text is available yet for this article.
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29315316/the-c3ar-promotes-macrophage-infiltration-and-regulates-anca-production-but-does-not-affect-glomerular-injury-in-experimental-anti-myeloperoxidase-glomerulonephritis
#13
Jonathan Dick, Poh-Yi Gan, A Richard Kitching, Stephen R Holdsworth
The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are autoimmune diseases associated with significant morbidity and mortality. They often affect the kidney causing rapidly progressive glomerulonephritis. While signalling by complement anaphylatoxin C5a though the C5a receptor is important in this disease, the role of the anaphylatoxin C3a signalling via the C3a receptor (C3aR) is not known. Using two different murine models of anti-myeloperoxidase (MPO) glomerulonephritis, one mediated by passive transfer of anti-MPO antibodies, the other by cell-mediated immunity, we found that the C3aR did not alter histological disease severity...
2018: PloS One
https://www.readbyqxmd.com/read/29314275/an-approach-to-the-asthma-protective-farm-effect-by-geocoding-good-farms-and-better-farms
#14
Susanne E K Müller-Rompa, Iana Markevych, Alexander J Hose, Georg Loss, Inge M Wouters, Jon Genuneit, Charlotte Braun-Fahrländer, Elisabeth Horak, Andrzej Boznanski, Dick Heederik, Erika von Mutius, Joachim Heinrich, Markus J Ege
BACKGROUND: The highly consistent association of growing up on a farm with a reduced asthma risk has so far been attributed to direct farm exposure. In contrast, geographical determinants of the larger environment have never been assessed. In this study, the effects of proximity to farms and environmental variables in relation to the residential address on asthma and atopy were assessed. METHODS: Addresses of 2,265 children of the Bavarian arm of the GABRIELA-study were converted into geocodes...
January 4, 2018: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/29311499/transcatheter-aortic-valve-implantation-tavi-for-native-aortic-valve-regurgitation%C3%A3-a-systematic-review
#15
Altayyeb Yousef, Zachary MacDonald, Trevor Simard, Juan J Russo, Joshua Feder, Michael V Froeschl, Alexander Dick, Christopher Glover, Ian G Burwash, Azeem Latib, Josep Rodés-Cabau, Marino Labinaz, Benjamin Hibbert
BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become the standard of care for management of high-risk patients with aortic stenosis. Limited data is available regarding the performance of TAVI in patients with native aortic valve regurgitation (NAVR).Methods and Results:We performed a systematic review from 2002 to 2016. The primary outcome was device success as per VARC-2 criteria. Secondary endpoints included procedural complications, and 30-day and 1-year mortality rates...
December 28, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29310963/guidance-on-noncorticosteroid-systemic-immunomodulatory-therapy-in-noninfectious-uveitis-fundamentals-of-care-for-uveitis-focus-initiative
#16
REVIEW
Andrew D Dick, James T Rosenbaum, Hassan A Al-Dhibi, Rubens Belfort, Antoine P Brézin, Soon Phaik Chee, Janet L Davis, Athimalaipet V Ramanan, Koh-Hei Sonoda, Ester Carreño, Heloisa Nascimento, Sawsen Salah, Sherveen Salek, Jay Siak, Laura Steeples
TOPIC: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. CLINICAL RELEVANCE: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. METHODS: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science)...
January 5, 2018: Ophthalmology
https://www.readbyqxmd.com/read/29306769/phase-ii-trial-of-ipilimumab-in-melanoma-patients-with-preexisting-humoural-immune-response-to-ny-eso-1
#17
G M Haag, I Zoernig, J C Hassel, N Halama, J Dick, N Lang, L Podola, J Funk, C Ziegelmeier, S Juenger, M Bucur, L Umansky, C S Falk, A Freitag, I Karapanagiotou-Schenkel, P Beckhove, A Enk, D Jaeger
BACKGROUND: Immune checkpoint therapy has dramatically changed treatment options in patients with metastatic melanoma. However, a relevant part of patients still does not respond to treatment. Data regarding the prognostic or predictive significance of preexisting immune responses against tumour antigens are conflicting. Retrospective data suggested a higher clinical benefit of ipilimumab in melanoma patients with preexisting NY-ESO-1-specific immunity. PATIENTS AND METHODS: Twenty-five patients with previously untreated or treated metastatic melanoma and preexisting humoural immune response against NY-ESO-1 received ipilimumab at a dose of 10 mg/kg in week 1, 4, 7, 10 followed by 3-month maintenance treatment for a maximum of 48 weeks...
January 4, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29306176/incidence-and-tumour-characteristics-of-bilateral-and-unilateral-interval-breast-cancers-at-screening-mammography
#18
Rob M G van Bommel, Adri C Voogd, Joost Nederend, Wikke Setz-Pels, Marieke W J Louwman, Luc J Strobbe, Dick Venderink, Vivianne C G Tjan-Heijnen, Lucien E M Duijm
BACKGROUND: Detected by screening mammography, bilateral breast cancer has a different pathological profile compared to unilateral breast cancer. We investigated the incidence of bilateral interval breast cancers and compared their characteristics with those of unilateral interval breast cancers. METHODS: We included all 468,720 screening mammograms of women who underwent biennial screening mammography in the South of the Netherlands between January 2005 and January 2015...
January 3, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29303393/high-risk-prescribing-to-medicaid-enrollees-receiving-opioid-analgesics-individual-and-county-level-factors
#19
Sara E Heins, Mark J Sorbero, Christopher M Jones, Andrew W Dick, Bradley D Stein
BACKGROUND: Prescription opioid overdoses have increased dramatically in recent years, with the highest rates among Medicaid enrollees. High-risk prescribing includes practices associated with overdoses and a range of additional opioid-related problems. OBJECTIVES: To identify individual- and county-level factors associated with high-risk prescribing among Medicaid enrollees receiving opioids. METHODS: In a four-states, cross-sectional claims data study, Medicaid enrollees 18-64 years old with a new opioid analgesic treatment episode 2007-2009 were identified...
January 5, 2018: Substance Use & Misuse
https://www.readbyqxmd.com/read/29303195/temperature-dependent-electronic-band-structure-of-wurtzite-gaas-nanowires
#20
Neimantas Vainorius, Simon Kubitza, Sebastian Lehmann, Lars Samuelson, Kimberly A Dick, Mats-Erik Pistol
It has recently become possible to grow GaAs in the wurtzite crystal phase. This ability allows interesting tests of band-structure theory. Wurtzite GaAs has two closely spaced direct conduction bands as well as three nondegenerate valence bands. The energies of the band edges are not well known, in particular not as a function of temperature. In order to improve the accuracy we have studied the temperature dependence of the conduction band minimum as well as of the second valence band maximum using resonant Raman scattering (of up to 3LO Raman lines)...
January 5, 2018: Nanoscale
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