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https://www.readbyqxmd.com/read/28425720/a-cereblon-modulator-cc-220-with-improved-degradation-of-ikaros-and-aiolos
#1
Mary E Matyskiela, Weihong Zhang, Hon-Wah Man, George Muller, Godrej Khambatta, Frans Baculi, Matthew Hickman, Laurie LeBrun, Barbra Pagarigan, Gilles Carmel, Chin-Chun Lu, Gang Lu, Mariko Riley, Yoshitaka Satoh, Peter Schafer, Thomas O Daniel, James Carmichael, Brian E Cathers, Philip P Chamberlain
The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis and relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher affinity than lenalidomide or pomalidomide. Consistent with this, the cellular degradation of Ikaros and Aiolos is more potent and the extent of substrate depletion is greater...
April 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28424581/cerebral-pathology-and-cognition-in-diabetes-the-merits-of-multiparametric-neuroimaging
#2
REVIEW
Frank C G van Bussel, Walter H Backes, Paul A M Hofman, Robert J van Oostenbrugge, Martin P J van Boxtel, Frans R J Verhey, Harry W M Steinbusch, Miranda T Schram, Coen D A Stehouwer, Joachim E Wildberger, Jacobus F A Jansen
Type 2 diabetes mellitus is associated with accelerated cognitive decline and various cerebral abnormalities visible on MRI. The exact pathophysiological mechanisms underlying cognitive decline in diabetes still remain to be elucidated. In addition to conventional images, MRI offers a versatile set of novel contrasts, including blood perfusion, neuronal function, white matter microstructure, and metabolic function. These more-advanced multiparametric MRI contrasts and the pertaining parameters are able to reveal abnormalities in type 2 diabetes, which may be related to cognitive decline...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28412953/quantification-of-task-dependent-cortical-activation-evoked-by-robotic-continuous-wrist-joint-manipulation-in-chronic-hemiparetic-stroke
#3
Martijn P Vlaar, Teodoro Solis-Escalante, Julius P A Dewald, Erwin E H van Wegen, Alfred C Schouten, Gert Kwakkel, Frans C T van der Helm
BACKGROUND: Cortical damage after stroke can drastically impair sensory and motor function of the upper limb, affecting the execution of activities of daily living and quality of life. Motor impairment after stroke has been thoroughly studied, however sensory impairment and its relation to movement control has received less attention. Integrity of the somatosensory system is essential for feedback control of human movement, and compromised integrity due to stroke has been linked to sensory impairment...
April 17, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/28412296/impact-of-higher-order-heme-degradation-products-on-hepatic-function-and-hemodynamics
#4
Raphael A Seidel, Thierry Claudel, Franziska A Schleser, Navin K Ojha, Matthias Westerhausen, Sandor Nietzsche, Christoph Sponholz, Frans Cuperus, Sina M Coldewey, Stefan H Heinemann, Georg Pohnert, Michael Trauner, Michael Bauer
BACKGROUND& AIMS: While, traditionally, biliverdin and bilirubin are considered end products of heme catabolism, there is evidence for further degradation to diverse bioactive products. As such, Z-BOX A and Z-BOX B arise upon oxidation with unknown implications for hepatocellular function and integrity. We studied the impact of Z-BOX A and B on hepatic functions and explored their alterations in health and cholestatic conditions. METHODS: Functional implications and mechanisms were investigated in rats, hepatocytic HepG2 and HepaRG cells, human immortalized hepatocytes, and isolated perfused livers...
April 12, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28412069/whole-exome-sequencing-identifies-biallelic-idh3a-variants-as-a-cause-of-retinitis-pigmentosa-accompanied-by-pseudocoloboma
#5
Laurence H M Pierrache, Adva Kimchi, Rinki Ratnapriya, Lisa Roberts, Galuh D N Astuti, Alexey Obolensky, Avigail Beryozkin, Martha J H Tjon-Fo-Sang, Jose Schuil, Caroline C W Klaver, Ernie M H F Bongers, Lonneke Haer-Wigman, Nicoline Schalij, Martijn H Breuning, Gratia M Fischer, Eyal Banin, Raj S Ramesar, Anand Swaroop, L Ingeborgh van den Born, Dror Sharon, Frans P M Cremers
PURPOSE: To identify the genetic cause of and describe the phenotype in 4 families with autosomal recessive retinitis pigmentosa (arRP) that can be associated with pseudocoloboma. DESIGN: Case series. PARTICIPANTS: Seven patients from 4 unrelated families with arRP, among whom 3 patients had bilateral early-onset macular pseudocoloboma. METHODS: We performed homozygosity mapping and whole-exome sequencing in 5 probands and 2 unaffected family members from 4 unrelated families...
April 12, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28410950/detection-of-anaplasma-spp-and-ehrlichia-spp-anibodies-and-dirofilaria-immitis-antigens-in-dogs-from-seven-locations-of-morocco
#6
Sarah Elhamiani Khatat, Khalid Khallaayoune, Nabil Errafyk, Frans Van Gool, Luc Duchateau, Sylvie Daminet, Malika Kachani, Hamid El Amri, Rahma Azrib, Hamid Sahibi
In Morocco no data has been published on canine exposure to Anaplasma spp., Borrrelia burgdorferi, and Ehrlichia spp., and only one report is available on the occurrence of Dirofilaria immitis in dogs. Therefore, the aim of this study was to collect current data on the canine exposure to these vector-borne pathogens (VBPs) in Morocco. A total of 217 urban (n=57), rural (n=110) and military (n=50) dogs from seven Moroccan locations were screened for Anaplasma spp., B. burgdorferi and Ehrlichia spp. antibodies and for D...
April 4, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28410681/simulation-of-scanner-and-patient-specific-low-dose-ct-imaging-from-existing-ct-images
#7
Robiël E Naziroglu, Vincent F van Ravesteijn, Lucas J van Vliet, Geert J Streekstra, Frans M Vos
PURPOSE: Simulating low-dose Computed Tomography (CT) facilitates in-silico studies into the required dose for a diagnostic task. Conventionally, low-dose CT images are created by adding noise to the projection data. However, in practice the raw data is often simply not available. This paper presents a new method for simulating patient-specific, low-dose CT images without the need of the original projection data. METHODS: The low-dose CT simulation method included the following: (1) computation of a virtual sinogram from a high dose CT image through a radon transform; (2) simulation of a 'reduced'-dose sinogram with appropriate amounts of noise; (3) subtraction of the high-dose virtual sinogram from the reduced-dose sinogram; (4) reconstruction of a noise volume via filtered back-projection; (5) addition of the noise image to the original high-dose image...
April 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/28409357/diffusion-weighted-mri-to-assess-response-to-chemoradiotherapy-in-rectal-cancer-main-interpretation-pitfalls-and-their-use-for-teaching
#8
Doenja M J Lambregts, Miriam M van Heeswijk, Andrea Delli Pizzi, Saskia G C van Elderen, Luisa Andrade, Nicky H G M Peters, Peter A M Kint, Margreet Osinga-de Jong, Shandra Bipat, Rik Ooms, Max J Lahaye, Monique Maas, Geerard L Beets, Frans C H Bakers, Regina G H Beets-Tan
OBJECTIVES: To establish the most common image interpretation pitfalls for non-expert readers using diffusion-weighted imaging (DWI) to assess response to chemoradiotherapy in patients with rectal cancer and to explore the use of these pitfalls in an expert teaching setting. METHODS: Two independent non-expert readers (R1 and R2) scored the restaging DW MRI scans (b1,000 DWI, in conjunction with ADC maps and T2-W MRI scans for anatomical reference) in 100 patients for the likelihood of a complete response versus residual tumour using a five-point confidence score...
April 13, 2017: European Radiology
https://www.readbyqxmd.com/read/28406318/a-low-dose-and-an-ultra-low-dose-contrast-agent-protocol-for-coronary-ct-angiography-in-a-clinical-setting-quantitative-and-qualitative-comparison-to-a-standard-dose-protocol
#9
Dominik C Benz, Christoph Gräni, Beatrice Hirt Moch, Fran Mikulicic, Jan Vontobel, Tobias A Fuchs, Julia Stehli, Olivier F Clerc, Mathias Possner, Aju P Pazhenkottil, Oliver Gaemperli, Ronny R Buechel, Philipp A Kaufmann
OBJECTIVES: To evaluate the impact of a low-dose (LD) and an ultra-low-dose (ULD) contrast protocol for coronary computed tomography angiography (CCTA) on qualitative and quantitative image parameters in a clinical setting. METHODS: We scanned 120 consecutive patients with a 256-slice CT scanner applying a LD (60 patients, 35-55mL) or ULD (60 patients, 25-45mL) contrast protocol adapted to body mass index (BMI). Visually assessed image quality as well as attenuation measured in each coronary segment were retrospectively compared to 20 consecutive patients scanned with a normal-dose (ND, 40-105mL) contrast protocol...
April 13, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28400091/metabolomic-changes-demonstrate-reduced-bioavailability-of-tyrosine-and-altered-metabolism-of-tryptophan-via-the-kynurenine-pathway-with-ingestion-of-medical-foods-in-phenylketonuria
#10
Denise M Ney, Sangita G Murali, Bridget M Stroup, Nivedita Nair, Emily A Sawin, Fran Rohr, Harvey L Levy
BACKGROUND: Deficiencies of the monoamine neurotransmitters, such as dopamine synthesized from Tyr and serotonin synthesized from Trp, are of concern in PKU. Our objective was to utilize metabolomics analysis to assess monoamine metabolites in subjects with PKU consuming amino acid medical foods (AA-MF) and glycomacropeptide medical foods (GMP-MF). METHODS: Subjects with PKU consumed a low-Phe diet combined with AA-MF or GMP-MF for 3weeks each in a randomized, controlled, crossover study...
April 6, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28399136/high-density-mapping-and-haplotype-analysis-of-the-major-stem-solidness-locus-sst1-in-durum-and-common-wheat
#11
Kirby T Nilsen, Amidou N'Diaye, P R MacLachlan, John M Clarke, Yuefeng Ruan, Richard D Cuthbert, Ron E Knox, Krystalee Wiebe, Aron T Cory, Sean Walkowiak, Brian L Beres, Robert J Graf, Fran R Clarke, Andrew G Sharpe, Assaf Distelfeld, Curtis J Pozniak
Breeding for solid-stemmed durum (Triticum turgidum L. var durum) and common wheat (Triticum aestivum L.) cultivars is one strategy to minimize yield losses caused by the wheat stem sawfly (Cephus cinctus Norton). Major stem-solidness QTL have been localized to the long arm of chromosome 3B in both wheat species, but it is unclear if these QTL span a common genetic interval. In this study, we have improved the resolution of the QTL on chromosome 3B in a durum (Kofa/W9262-260D3) and common wheat (Lillian/Vesper) mapping population...
2017: PloS One
https://www.readbyqxmd.com/read/28397664/-talaromyces-marneffei-fungaemia-in-a-patient-from-thailand-with-newly-diagnosed-hiv
#12
Marie Nørredam, Anders Porskrog, Lukas Frans Ocias, Jenny Dahl Knudsen
Talaromyces marneffei is a dimorphic fungus, which may cause life-threatening opportunistic infections in immuno-compromised individuals. A 25-year-old woman from Thailand was admitted with fever, shortness of breath, cough, and weight loss. The symptoms had persisted for three weeks. The patient had a stopover in Copenhagen on her way to Thailand from Greenland. A thoracic X-ray showed bilateral interstitial changes. Examinations showed positive HIV-test with a CD4-count of 21/microlitre. Moreover, fungaemia with T...
February 20, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28393672/radiation-awareness-for-endovascular-abdominal-aortic-aneurysm-repair-in-the-hybrid-operating-room-an-instant-patient-risk-chart-for-daily-practice
#13
Quirina M de Ruiter, Crystel M Gijsberts, Constantijn E Hazenberg, Frans L Moll, Joost A van Herwaarden
PURPOSE: To determine which patient and C-arm characteristics are the strongest predictors of intraoperative patient radiation dose rates (DRs) during endovascular aneurysm repair (EVAR) procedures and create a patient risk chart. METHODS: A retrospective analysis was performed of 74 EVAR procedures, including 16,889 X-ray runs using fixed C-arm imaging equipment. Four multivariate log-linear mixed models (with patient as a random effect) were constructed. Mean air kerma DR (DRAK, mGy/s) and the mean dose area product DR (DRDAP, mGycm(2)/s) were the outcome variables utilized for fluoroscopy as differentiated from digital subtraction angiography (DSA)...
April 1, 2017: Journal of Endovascular Therapy
https://www.readbyqxmd.com/read/28393125/planning-nature-in-urbanized-countries-an-analysis-of-monetary-and-non-monetary-impacts-of-conservation-policy-scenarios-in-the-netherlands
#14
Frans J Sijtsma, Willem G M van der Bilt, Arjen van Hinsberg, Bart de Knegt, Martijn van der Heide, Hans Leneman, René Verburg
Planning and conserving nature areas are challenging tasks in urbanized and intensively used countries like the Netherlands. This paper supports decision making and public policy debate about these tasks in both an empirical and a methodological way. Empirically, we explore policy alternatives by determining the potential consequences of different nature policy scenarios in the Netherlands. Methodologically, we employ a mixed monetary and non-monetary evaluation method known as multi-criteria cost-benefit analysis (MCCBA)...
March 2017: Heliyon
https://www.readbyqxmd.com/read/28390747/fcrl4-b-cells-in-salivary-glands-of-primary-sj%C3%A3-gren-s-syndrome-patients
#15
Erlin A Haacke, Hendrika Bootsma, Fred K L Spijkervet, Annie Visser, Arjan Vissink, Philip M Kluin, Frans G M Kroese
Fc receptor-like protein 4 (FcRL4) is normally expressed on a small subset of mucosa-associated B-cells, as well as on mucosa-associated lymphoid tissue (MALT) lymphoma B-cells. Primary Sjögren's syndrome (pSS) patients have an increased risk of developing MALT lymphomas, preferentially in the parotid glands. For this reason we studied here by immunohistochemistry and mRNA analysis whether FcRL4 expressing B-cells are present in salivary gland tissue (labial and parotid) of pSS patients (n = 54) and non-pSS sicca patients (n = 16) and whether parotid gland MALT lymphomas in pSS patients (n = 49) also express this receptor...
April 5, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28388055/development-and-validation-of-ion-chromatography-tandem-mass-spectrometry-based-method-for-the-multiresidue-determination-of-polar-ionic-pesticides-in-food
#16
Stuart Adams, Jonathan Guest, Michael Dickinson, Richard J Fussell, Jonathan Beck, Frans Schoutsen
An extraction method using acidified methanol based on the quick polar pesticide (QuPPe) method using suppressed ion chromatography coupled to mass spectrometry was developed and validated for the direct analysis of polar pesticides, without the need for derivatization or ion pairing, in cereals and grapes. The method was robust, and results for glyphosate, aminomethyl phosphonic acid (AMPA), N-acetyl-AMPA, glufosinate, 3-methylphosphinicopropionic acid (3-MPPA), N-acetyl glufosinate, ethephon, chlorate, perchlorate, fosetyl aluminum, and phosphonic acid at three concentration levels (typically 0...
April 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28386433/historical-gene-flow-constraints-in-a-northeastern-atlantic-fish-phylogeography-of-the-ballan-wrasse-labrus-bergylta-across-its-distribution-range
#17
Frederico Almada, Sara M Francisco, Cristina S Lima, Richard FitzGerald, Luca Mirimin, David Villegas-Ríos, Fran Saborido-Rey, Pedro Afonso, Telmo Morato, Sérgio Bexiga, Joana I Robalo
The distribution and demographic patterns of marine organisms in the north Atlantic were largely shaped by climatic changes during the Pleistocene, when recurrent glacial maxima forced them to move south or to survive in northern peri-glacial refugia. These patterns were also influenced by biological and ecological factors intrinsic to each species, namely their dispersion ability. The ballan wrasse (Labrus bergylta), the largest labrid fish along Europe's continental margins, is a target for fisheries and aquaculture industry...
February 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28384835/validation-of-the-automated-electronic-microemboli-detection-system-in-patients-undergoing-carotid-endarterectomy
#18
Tesse Leunissen, Daniel van Vriesland, Hester den Ruijter, Frans Moll, Werner Mess, Gert Jan de Borst
Purpose To assess the diagnostic value of automatic embolus detection software (AEDS) in transcranial Doppler (TCD) monitoring for the detection of solid microemboli in patients at risk for perioperative stroke during carotid endarterectomy (CEA). Materials and Methods In 50 patients undergoing CEA, perioperative TCD registration was recorded. All recorded events, identified and saved by the AEDS, were analyzed off-line doubly by two human experts (HEs) within a time frame of > 4 months. The inter- and intraobserver variability was assessed...
April 6, 2017: Ultraschall in der Medizin
https://www.readbyqxmd.com/read/28382003/adult-lysophosphatidic-acid-receptor-1-deficient-rats-with-hyperoxia-induced-neonatal-chronic-lung-disease-are-protected-against-lipopolysaccharide-induced-acute-lung-injury
#19
Xueyu Chen, Frans J Walther, El H Laghmani, Annemarie M Hoogeboom, Anne C B Hogen-Esch, Ingrid van Ark, Gert Folkerts, Gerry T M Wagenaar
Aim: Survivors of neonatal chronic lung disease or bronchopulmonary dysplasia (BPD) suffer from compromised lung function and are at high risk for developing lung injury by multiple insults later in life. Because neonatal lysophosphatidic acid receptor-1 (LPAR1)-deficient rats are protected against hyperoxia-induced lung injury, we hypothesize that LPAR1-deficiency may protect adult survivors of BPD from a second hit response against lipopolysaccharides (LPS)-induced lung injury. Methods: Directly after birth, Wistar control and LPAR1-deficient rat pups were exposed to hyperoxia (90%) for 8 days followed by recovery in room air...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28381814/economic-evaluation-of-an-intervention-program-with-the-aim-to-improve-at-work-productivity-for-workers-with-rheumatoid-arthritis
#20
Cindy Noben, Myrthe van Vilsteren, Cécile Boot, Romy Steenbeek, Dirkjan van Schaardenburg, Johannes R Anema, Silvia Evers, Frans Nijhuis, Angelique de Rijk
OBJECTIVES: Evaluating the cost effectiveness and cost utility of an integrated care intervention and participatory workplace intervention for workers with rheumatoid arthritis (RA) to improve their work productivity. METHODS: Twelve month follow-up economic evaluation alongside a randomized controlled trial (RCT) within specialized rheumatology treatment centers. Adults diagnosed with RA between 18-64 years, in a paid job for at least eight hours per week, experiencing minor difficulties in work functioning were randomized to the intervention (n = 75) or the care-as-usual (CAU) group (n = 75)...
April 5, 2017: Journal of Occupational Health
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