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Xiao-Feng Xiong, Hang Zhang, Christina R Underwood, Kasper Harpsøe, Thomas J Gardella, Mie F Wöldike, Michael Mannstadt, David E Gloriam, Hans Bräuner-Osborne, Kristian Strømgaard
G proteins are key mediators of G protein-coupled receptor signalling, which facilitates a plethora of important physiological processes. The cyclic depsipeptides YM-254890 and FR900359 are the only known specific inhibitors of the Gq subfamily of G proteins; however, no synthetic route has been reported previously for these complex natural products and they are not easily isolated from natural sources. Here we report the first total synthesis of YM-254890 and FR900359, as well as of two known analogues, YM-385780 and YM-385781...
November 2016: Nature Chemistry
Henrik Hasle, Gertjan J L Kaspers
Over the last four decades the survival of paediatric patients with acute myeloid leukaemia has gradually increased to 70% in high-income countries. The therapy is very intensive and associated with many acute and long-term side effects. The early death rate has been reduced to 1-4%. The acute toxicity is a limiting factor for improving survival in low-income countries. Transplant is associated with more endocrinological late effects while cardiotoxicity is more common after relapse. Reducing the physical costs of therapy without jeopardizing survival may be accomplished by optimal supportive care, less cardiotoxic anthracyclines, less consolidation courses and strict indications for stem cell transplantation...
October 21, 2016: British Journal of Haematology
Javier Ochoa-Repáraz, Sara L Colpitts, Christopher Kircher, Eli J Kasper, Kiel M Telesford, Sakhina Begum-Haque, Anudeep Pant, Lloyd H Kasper
OBJECTIVE: To determine whether as an orally delivered treatment, teriflunomide, an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase approved to treat relapsing forms of multiple sclerosis, could affect gut-associated lymphoid tissue (GALT) immune responses functionally. METHODS: C57BL/6 mice were treated orally with teriflunomide and flow cytometric analysis of immune GALT cells performed ex vivo, and adoptive transfer experiments were used to test the protective effects of GALT regulatory T (Treg) cells...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Marc Jansen, Sophie Em Veldhuijzen van Zanten, Dannis G Van Vuurden, Marc Huisman, Danielle J Vugts, Otto S Hoekstra, Guus A M S van Dongen, Gert-Jan Jl Kaspers
: Predictive tools to guide therapy in children with brain tumors are urgently needed. We introduced molecular imaging to facilitate this. We investigated whether bevacizumab can reach the tumor in children with diffuse intrinsic pontine glioma (DIPG) by measuring the tumor uptake of zirconium-89((89)Zr)-labeled bevacizumab by PET. In addition we evaluated the safety of the procedure in children and determined the optimal timing of imaging. METHODS: Patients received 0...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Kasper D Tidemand, Hans E M Christensen, Niclas Hoeck, Pernille Harris, Jane Boesen, Günther H Peters
Tryptophan hydroxylase 2 (TPH2) catalyses the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression, obsessive compulsive disorder, and schizophrenia. Full-length TPH2 is poorly characterized due to low purification quantities caused by its inherent instability. Three truncated variants of human TPH2 (rch TPH2; regulatory and catalytic domain, NΔ47-rch TPH2; truncation of 47 residues in the N terminus of rch TPH2, and ch TPH2; catalytic domain) were expressed, purified, and examined for changes in transition temperature, inactivation rate, and oligomeric state...
October 2016: FEBS Open Bio
Kasper Raus
BACKGROUND: When a new intervention or drug is developed, this has to pass through various phases of clinical testing before it achieves market approval, which can take many years. This raises an issue for drugs which could benefit terminally ill patients. These patients might set their hopes on the experimental drug but are unable to wait since they are likely to pass away before the drug is available. As a means of nevertheless getting access to experimental drug, many seriously ill and terminally ill patients are therefore very willing to participate in randomised controlled trials...
October 18, 2016: BMC Medical Ethics
Pia Baldinger-Melich, Ana Weidenauer, Christoph Linder, Marius Hienert, Siegfried Kasper, Mara Stamenkovic, Matthäus Willeit
No abstract text is available yet for this article.
October 7, 2016: Journal of ECT
Irsan E Kooi, Saskia E van Mil, David MacPherson, Berber M Mol, Annette C Moll, Hanne Meijers-Heijboer, Gertjan J L Kaspers, Jacqueline Cloos, Hein Te Riele, Josephine C Dorsman
Several murine retinoblastoma models have been generated by deleting the genes encoding for retinoblastoma susceptibility protein pRb and one of its family members p107 or p130. In Rb(-/-) p107(-/-) retinoblastomas, somatic copy number alterations (SCNAs) like Mdm2 amplification or Cdkn2a deletion targeting the p53-pathway occur, which is uncommon for human retinoblastoma. In our study, we determined SCNAs in retinoblastomas developing in Rb(-/-) p130(-/-) mice and compared this to murine Rb(-/-) p107(-/-) tumors and human tumors...
October 17, 2016: Genes, Chromosomes & Cancer
D L McCue, J M Kasper, J D Hommel
BACKGROUND: Motivation for high-fat food is thought to contribute to excess caloric intake in obese individuals. A novel regulator of motivation for food may be Neuromedin U (NMU), a highly-conserved neuropeptide which influences food intake. Although these effects of NMU have primarily been attributed to signaling in the paraventricular nucleus of the hypothalamus (PVN), NMU has also been found in other brain regions involved in both feeding behavior and motivation. We investigate the effects of NMU on motivation for food and food intake, and identify the brain regions mediating these effects...
October 17, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Rene Seiger, Andreas Hahn, Allan Hummer, Georg S Kranz, Sebastian Ganger, Michael Woletz, Christoph Kraus, Ronald Sladky, Alexander Kautzky, Siegfried Kasper, Christian Windischberger, Rupert Lanzenberger
Sex-steroid hormones are primarily involved in sexual differentiation and development and are thought to underlie processes related to cognition and emotion. However, divergent results have been reported concerning the effects of hormone administration on brain structure including side effects like brain atrophy and dementia. Cross-sex hormone therapy in transgender subjects offers a unique model for studying the effects of sex hormones on the living human brain. In this study, 25 Female-to-Male (FtM) and 14 Male-to-Female (MtF) subjects underwent MRI examinations at baseline and after a period of at least 4-months of continuous cross-sex hormone administration...
October 5, 2016: Psychoneuroendocrinology
Adam Ali Ghotbi, Andreas Kjaer, Lars Nepper-Christensen, Kiril Aleksov Ahtarovski, Jacob Thomsen Lønborg, Niels Vejlstrup, Kasper Kyhl, Thomas Emil Christensen, Thomas Engstrøm, Henning Kelbæk, Lene Holmvang, Lia E Bang, Rasmus Sejersten Ripa, Philip Hasbak
BACKGROUND: Determining infarct size and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) is important when assessing the efficacy of new reperfusion strategies. We investigated whether rest (82)Rb-PET myocardial perfusion imaging can estimate area at risk, final infarct size, and myocardial salvage index when compared to cardiac SPECT and magnetic resonance (CMR). METHODS: Twelve STEMI patients were injected with (99m)Tc-Sestamibi intravenously immediate prior to reperfusion...
October 14, 2016: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
Xiaowen Feng, Jun-Liang Liu, Kasper S Pedersen, Joscha Nehrkorn, Alexander Schnegg, Karsten Holldack, Jesper Bendix, Marc Sigrist, Hannu Mutka, Dumitru Samohvalov, David Aguilà, Ming-Liang Tong, Jeffrey R Long, Rodolphe Clérac
The mononuclear complex (Bu4N)2[Re(IV)Cl4(CN)2]·2DMA (DMA = N,N-dimethylacetamide) displays intricate magnetization dynamics, implying Orbach, direct, and Raman-type relaxation processes. The Orbach relaxation process is characterized by an energy barrier of 39 K (27 cm(-1)) that is discussed based on high-field electron paramagnetic resonance (EPR), inelastic neutron scattering and frequency-domain THz EPR investigations.
October 14, 2016: Chemical Communications: Chem Comm
Xin Li, Yun Liu, Tal Salz, Kasper D Hansen, Andrew P Feinberg
DNA methylation at the 5-postion of cytosine (5mC) is an epigenetic modification that regulates gene expression and cellular plasticity in development and disease. The ten-eleven translocation (TET) gene family oxidizes 5mC to 5-hydroxymethylcytosine (5hmC), providing an active mechanism for DNA demethylation, and may also provide its own regulatory function. Here we applied oxidative bisulfite sequencing to generate whole-genome DNA methylation and hydroxymethylation maps at single-base resolution in paired human liver and lung normal and cancer...
October 13, 2016: Genome Research
Pernille Svendsen, Nitesh Shekhrajka, Kasper Lindblad Nielsen, Peter Vestergaard, Mette Østergaard Poulsen, Anders Krog Vistisen, Peter Svenssen Munksgaard, Marianne Tang Severinsen, Paw Jensen, Hans Erik Johnsen, Lasse Hjort Jakobsen, Martin Bøgsted, Jens Brøndum Frøkjær, Tarec Christoffer El-Galaly
Treatment of diffuse large B-cell lymphoma (DLBCL) with R-CHOP(-like) regimens include large cumulative doses of prednisolone. In this retrospective study, we evaluated changes in vertebral bone density (VD) in DLBCL patients by measuring CT-ascertained Hounsfield units (HU) at the L3 level. In total, 111 patients diagnosed from 2007 to 2012 and response assessed following first line treatment were included. Post-treatment VD was significantly reduced to 86% of pretreatment VD on average (p < .001). Neither female sex nor high age (>70 years) were significantly associated with greater post-treatment VD reduction...
October 13, 2016: Leukemia & Lymphoma
K I Braam, E M van Dijk-Lokkart, J M van Dongen, R R L van Litsenburg, T Takken, J Huisman, J H M Merks, J E Bosmans, N A G Hakkenbrak, M B Bierings, M M van den Heuvel-Eibrink, M A Veening, E van Dulmen-den Broeder, G J L Kaspers
This study was performed to estimate the cost-effectiveness of a combined physical exercise and psychosocial intervention for children with cancer compared with usual care. Sixty-eight children, aged 8-18 years old, during or within the first year post-cancer treatment were randomised to the intervention (n = 30) and control group (n = 38). Health outcomes included fitness, muscle strength and quality adjusted life years; all administered at baseline, 4- and 12-month follow-up. Costs were gathered by 1 monthly cost questionnaires over 12 months, supplemented by medication data obtained from pharmacies...
October 10, 2016: European Journal of Cancer Care
Rasmus Bo Hasselbalch, Louis Lind Plesner, Mia Pries-Heje, Lisbet Ravn, Morten Lind, Rasmus Greibe, Birgitte Nybo Jensen, Lars S Rasmussen, Kasper Iversen
BACKGROUND: Crowding in the emergency department (ED) is a well-known problem resulting in an increased risk of adverse outcomes. Effective triage might counteract this problem by identifying the sickest patients and ensuring early treatment. In the last two decades, systematic triage has become the standard in ED's worldwide. However, triage models are also time consuming, supported by limited evidence and could potentially be of more harm than benefit. The aim of this study is to develop a quicker triage model using data from a large cohort of unselected ED patients and evaluate if this new model is non-inferior to an existing triage model in a prospective randomized trial...
October 10, 2016: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
Kasper Linde Ankjærgaard, Daniel Bech Rasmussen, Signe Høyer Schwaner, Helle Frost Andreassen, Ejvind Frausing Hansen, Jon Torgny Wilcke
In severe COPD, patients having survived acute hypercapnic respiratory failure (AHRF) treated with noninvasive ventilation (NIV) have a high mortality and risk of readmissions. The aim was to analyze the prognosis for patients with COPD having survived AHRF and to assess whether previous admissions with NIV predict new ones.We conducted a retrospective follow-up analysis of 201 patients two years after NIV treatment of AHRF. Comparison of time-to-event in patients previously treated with NIV versus patients with no previous NIV treatment...
October 10, 2016: COPD
Nikolaj Hjort Schmidt, Kasper Hansen, Henrik Lauridsen, Annie Vesterby, Jens Randel Nyengaard, Alf Brubakk, Michael Pedersen
OBJECTIVE: The most common complications of hyperbaric oxygen treatment (HBOT) are related to pressure changes on gas-containing cavities. Therefore, inability to auto-inflate the middle ear may result in transient or permanent hearing loss. However, it seems that middle ear barotrauma (MEBt) does not develop more often in mechanically ventilated patients than in ambulatory patients. This might be explained by deep sedation of these patients. Therefore, the aim of this study was to determine whether anaesthesia and/or neuromuscular blockade can influence Eustachian tube (ET) function...
September 2016: Diving and Hyperbaric Medicine: the Journal of the South Pacific Underwater Medicine Society
Kasper T Møller, Alexander S Fogh, Mark Paskevicius, Jørgen Skibsted, Torben R Jensen
Metal borides are often decomposition products from metal borohydrides and thus play a role in the reverse reaction where hydrogen is absorbed. In this work, aluminium boride, AlB2, has been investigated as a boron source for the formation of borohydrides under hydrogen pressures of p(H2) = 100 or 600 bar at elevated temperatures (350 or 400 °C). The systems AlB2-MHx (M = Li, Na, Mg, Ca) have been investigated, producing LiBH4, NaBH4 and Ca(BH4)2, whereas the formation of Mg(BH4)2 was not observed at T = 400 °C and p(H2) = 600 bar...
October 5, 2016: Physical Chemistry Chemical Physics: PCCP
Karin Ortmayr, Verena Charwat, Cornelia Kasper, Stephan Hann, Gunda Koellensperger
The p-value is the most prominent established metric for statistical significance in non-targeted metabolomics. However, its adequacy has repeatedly been the subject of discussion criticizing its uncertainty and its dependence on sample size and statistical power. These issues compromise non-targeted metabolomics in model systems, where studies typically investigate 5-10 samples per group. In this paper we propose a different approach for assessing the relevance of fold change (FC) data, where the FC is treated as a quantitative value and is validated by uncertainty budgeting...
October 6, 2016: Analyst
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