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Nina Zila, Andrea Bileck, Besnik Muqaku, Lukas Janker, Ossia M Eichhoff, Phil F Cheng, Reinhard Dummer, Mitchell P Levesque, Christopher Gerner, Verena Paulitschke
Background: MAP kinase inhibitor (MAPKi) therapy for BRAF mutated melanoma is characterized by high response rates but development of drug resistance within a median progression-free survival (PFS) of 9-12 months. Understanding mechanisms of resistance and identifying effective therapeutic alternatives is one of the most important scientific challenges in melanoma. Using proteomics, we want to specifically gain insight into the pathophysiological process of cerebral metastases. Methods: Cerebral metastases from melanoma patients were initially analyzed by a LC-MS shotgun approach performed on a QExactive HF hybrid quadrupole-orbitrap mass spectrometer...
2018: Clinical Proteomics
Mary Courtney Moore, David E Kelley, Raul C Camacho, Peter Zafian, Tian Ye, Songnian Lin, Niels C Kaarsholm, Ravi Nargund, Terri M Kelly, Margaret Van Heek, Stephen F Previs, Christopher Moyes, Marta S Smith, Ben Farmer, Phil Williams, Alan D Cherrington
We evaluated the hepatic and nonhepatic responses to glucose-responsive insulin (GRI). Eight dogs received GRI or regular human insulin (HI) in random order. A primed, continuous intravenous infusion of [3-3 H]glucose began at -120 min. Basal sampling (-30 to 0 min) was followed by 2 study periods (150 min each), P1 and P2. At 0 min, somatostatin and GRI (36±3 pmol/kg/min) or HI (1.8 pmol/kg/min) were infused IV; basal glucagon was replaced intraportally. Glucose was infused intravenously to clamp plasma glucose at 80 mg/dL (P1) and 240 mg/dL (P2)...
March 14, 2018: Diabetes
Manuela Germeshausen, Phil Ancliff, Jaime Estrada, Markus Metzler, Eva Ponstingl, Horst Rütschle, Dirk Schwabe, Richard H Scott, Sule Unal, Angela Wawer, Bernward Zeller, Matthias Ballmaier
Heterozygous mutations in MECOM (MDS1 and EVI1 complex locus) have been reported to be causative of a rare association of congenital amegakaryocytic thrombocytopenia and radioulnar synostosis. Here we report on 12 patients with congenital hypomegakaryocytic thrombocytopenia caused by MECOM mutations (including 10 novel mutations). The mutations affected different functional domains of the EVI1 protein. The spectrum of phenotypes was much broader than initially reported for the first 3 patients; we found familial as well as sporadic cases, and the clinical spectrum ranged from isolated radioulnar synostosis with no or mild hematological involvement to severe bone marrow failure without obvious skeletal abnormality...
March 27, 2018: Blood Advances
Howard Bauchner, Phil B Fontanarosa
No abstract text is available yet for this article.
March 13, 2018: JAMA: the Journal of the American Medical Association
Cristina Menni, Ivan Gudelj, Erin MacDonald-Dunlop, Massimo Mangino, Jonas Zierer, Erim Bešić, Peter Joshi, Irena Trbojević-Akmačić, Phil J Chowienczyk, Timothy D Spector, James F Wilson, Gordan Lauc, Ana M Valdes
<u>Rationale:</u> One measure of protein glycosylation (GlycA) has been reported to predict higher cardiovascular risk by reflecting inflammatory pathways <u>Objective:</u> To assess the role of a comprehensive panel of immunoglobulin (IgG) glycosylation traits on traditional risk factors for cardiovascular disease and on presence of subclinical atherosclerosis in addition to GlycA. <u>Methods and Results:</u> We measured 76 IgG glycosylation traits in 2970 women (age range 40-79 years) from the TwinsUK cohort and correlated it to their estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk score and their carotid and femoral plaque measured by ultrasound imaging...
March 13, 2018: Circulation Research
Fotis Spyropoulos, Daniel Kurukji, Phil Taylor, Ian T Norton
Aside from single active microencapsulation, there is growing interest in designing structures for the co-encapsulation and co-delivery of multiple species. Although currently achievable within solid systems, significant challenges exist in realising such functionality in liquid formulations. The present study reports on a novel microstructural strategy that enables the co-encapsulation and co-release of two actives from oil-in-water emulsions. This is realised through the fabrication of sodium caseinate/chitosan (NaCAS/CS) complexes that in tandem function as encapsulants of one active (hydrophilic) but also as ('Pickering-like') stabilisers to emulsion droplets containing a secondary active (hydrophobic)...
March 13, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Kristina Glenske, Phil Donkiewicz, Alexander Köwitsch, Nada Milosevic-Oljaca, Patrick Rider, Sven Rofall, Jörg Franke, Ole Jung, Ralf Smeets, Reinhard Schnettler, Sabine Wenisch, Mike Barbeck
The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum . In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials...
March 12, 2018: International Journal of Molecular Sciences
Katherine Murphy, Tim Cooksley, Phil Haji-Michael
Background: There has been a significant increase in the number of patients presenting with cancer related emergencies and potentially requiring critical care admission. Aim: To analyse the short and long term outcomes of patients with solid tumours requiring unplanned medical admission to a specialist cancer intensive care unit (ICU). Design: An unplanned cohort study. Methods: A retrospective analysis of patients admitted to a United Kingdom specialist tertiary oncology CCU between September 2009 and September 2015...
March 9, 2018: QJM: Monthly Journal of the Association of Physicians
Liz Potterton, Jon Agirre, Charles Ballard, Kevin Cowtan, Eleanor Dodson, Phil R Evans, Huw T Jenkins, Ronan Keegan, Eugene Krissinel, Kyle Stevenson, Andrey Lebedev, Stuart J McNicholas, Robert A Nicholls, Martin Noble, Navraj S Pannu, Christian Roth, George Sheldrick, Pavol Skubak, Johan Turkenburg, Ville Uski, Frank von Delft, David Waterman, Keith Wilson, Martyn Winn, Marcin Wojdyr
The CCP4 (Collaborative Computational Project, Number 4) software suite for macromolecular structure determination by X-ray crystallography groups brings together many programs and libraries that, by means of well established conventions, interoperate effectively without adhering to strict design guidelines. Because of this inherent flexibility, users are often presented with diverse, even divergent, choices for solving every type of problem. Recently, CCP4 introduced CCP4i2, a modern graphical interface designed to help structural biologists to navigate the process of structure determination, with an emphasis on pipelining and the streamlined presentation of results...
February 1, 2018: Acta Crystallographica. Section D, Structural Biology
Samuel T Orange, Phil Marshall, Leigh A Madden, Rebecca V Vince
This study compared the effects of a 4-week supervised (SUP) and unsupervised (UNSUP) resistance training programme followed by 12 weeks of detraining (DET). Thirty-six healthy aging adults (age: 53.6 ± 3.6 years; body mass index: 28.3 ± 5.1 kg/m) were randomly allocated to a SUP group (n = 17) or an UNSUP group (n = 19). Participants completed three training sessions per week using resistance bands and body weight movements. Measures of physical performance were administered at baseline, at the end of the training programme, and after the DET period...
March 6, 2018: Journal of Strength and Conditioning Research
Seok Jong Chung, Han Soo Yoo, Jungsu S Oh, Jae Seung Kim, Byoung Seok Ye, Young H Sohn, Phil Hyu Lee
INTRODUCTION: To investigate the relationship between the sub-regional pattern of striatal dopamine depletion and cognitive impairment in early-stage Parkinson's disease (PD), and determine the effect of striatal dopamine density on cognitive prognosis. METHODS: Patients with drug-naïve non-demented PD were divided into mild cognitive impairment (PD-MCI; n = 129) and cognitively normal (PD-CogN; n = 182) groups. Using quantification of the dopamine transporter (DAT) availability in each striatal sub-region with18 F-FP-CIT PET scans, we performed inter-group comparative analysis of DAT availability and multivariate linear regression analysis to assess the association between DAT availability and cognitive performance...
March 2, 2018: Parkinsonism & related Disorders
Christian Maurer, Jonathan Baré, Jolanta Kusmierczyk-Michulec, Alice Crawford, Paul W Eslinger, Petra Seibert, Blake Orr, Anne Philipp, Ole Ross, Sylvia Generoso, Pascal Achim, Michael Schoeppner, Alain Malo, Anders Ringbom, Olivier Saunier, Denis Quèlo, Anne Mathieu, Yuichi Kijima, Ariel Stein, Tianfeng Chai, Fong Ngan, Susan J Leadbetter, Pieter De Meutter, Andy Delcloo, Rich Britton, Ashley Davies, Lee G Glascoe, Donald D Lucas, Matthew D Simpson, Phil Vogt, Martin Kalinowski, Theodore W Bowyer
After performing a first multi-model exercise in 2015 a comprehensive and technically more demanding atmospheric transport modelling challenge was organized in 2016. Release data were provided by the Australian Nuclear Science and Technology Organization radiopharmaceutical facility in Sydney (Australia) for a one month period. Measured samples for the same time frame were gathered from six International Monitoring System stations in the Southern Hemisphere with distances to the source ranging between 680 (Melbourne) and about 17,000 km (Tristan da Cunha)...
March 8, 2018: Journal of Environmental Radioactivity
Nicholas H Chakirya, Phil W Raess, Kevin Turner, Jason C Hedges, Jen-Jane Liu
Malignant Leydig cell tumor is a rare entity that has been previously described as rapidly progressive and uniformly fatal. We present the case of a malignant Leydig cell tumor that presented 14 years after orchiectomy with an isolated retroperitoneal metastasis. Our patient underwent a retroperitoneal lymph node dissection and has been free of recurrence or progression at 12 months of follow up. Additionally, we describe the symptomatic hormone dysfunction experienced by our patient as a result of his tumor...
February 2018: Canadian Journal of Urology
Phil Shaw
With the UK's first high-energy Proton Beam Therapy Centre set to open next year at Manchester's The Christie, young patients with head and neck tumours, cancers close to the skull or spine, or a variety of soft tissue tumours, and adults with cancers difficult to treat using 'conventional' photon-based radiotherapy will, for the first time, be able to receive NHS proton beam therapy (PBT) without having to travel overseas. HEJ editor, Jonathan Baillie, visited the site of The Christie's new £135 million PBT Centre to find out more about the design and construction of a facility which interserve construction director for the North-West, Phil Shaw, describes as one of the most complex and specialist he has worked on...
May 2017: Health Estate
Jessica Snowden, Paul Darden, Paul Palumbo, Phil Saul, Jeannette Lee
PURPOSE OF REVIEW: The institutional development award (IDeA) program was created to increase the competitiveness of investigators in states with historically low success rates for National Institutes of Health (NIH) research funding applications. IDeA states have high numbers of rural and medically underserved residents with disproportionately high rates of infant mortality, obesity, and poverty. This program supports the development and expansion of research infrastructure and research activities in these states...
April 2018: Current Opinion in Pediatrics
Hayley Simon, Giannantonio Cibin, Phil Robbins, Sarah Day, Chiu Tang, Ian Freestone, Eleanor Schofield
Post-excavation iron corrosion may be accelerated by the presence of Cl- , leading to conservation methods designed to remove Cl. This study exploits a unique opportunity to assess 35 years of conservation applied to cast-iron cannon shot excavated from the Mary Rose. A combination of synchrotron X-ray powder diffraction (SXPD), absorption spectroscopy (XAS), and fluorescence (XRF) mapping have been used to characterise the impact of conservation on the crystalline corrosion products, chlorine distribution, and speciation...
March 8, 2018: Angewandte Chemie
Samuel O Adegbola, Anthea Pisani, Kapil Sahnan, Phil Tozer, Pierre Ellul, Janindra Warusavitarne
Crohn's disease is increasingly thought to encompass multiple possible phenotypes. Perianal manifestations account for one such phenotype and represent an independent disease modifier. In its more severe form, perianal Crohn's disease confers a higher risk of a severe and disabling disease course, relapses, hospital admissions and operations. This, in turn, imposes a considerable burden and disability on patients. Identification of the precise manifestation is important, as management is nuanced, with both medical and surgical components, and is best undertaken in a multidisciplinary setting for both diagnosis and ongoing treatment...
March 2018: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
Justin G Hollands, Phil Terhaar, Nada J Pavlovic
OBJECTIVE: We sought to determine the joint influence of resolution, target range, and image contrast on the detection and identification of targets in simulated naturalistic scenes. BACKGROUND: Resolution requirements for target acquisition have been developed based on threshold values obtained using imaging systems, when target range was fixed, and image characteristics were determined by the system. Subsequent work has examined the influence of factors like target range and image contrast on target acquisition...
March 1, 2018: Human Factors
Ricardo Garay, Carlos A Zarate, Icilio Cavero, Yong-Ku Kim, Thomas Charpeaud, Phil Skolnick
No abstract text is available yet for this article.
March 1, 2018: Drug Discovery Today
In Sun Kim, Hyeon-Soo Kim, Minjoo Kim, Jeongil Kwon, Eun-Mi Kim, Hyosook Hwang, Phil-Sun Oh, Seok Tae Lim, Myung-Hee Sohn, Dong Hyun Kim, Hwan-Jeong Jeong
Histone deacetylases (HDACs) are an important regulator of expression and activity of numerous proteins in terms of epigenetic aberrations. This makes HDACs attractive for antitumor therapy and imaging in certain cancers. The authors report the radiochemical synthesis of 2-[18 F]fluoroethyltriazolesuberohydroxamine acid ([18 F]FETSAHA) as a HDAC-targeted radiolabel probe for positron imaging tomography/computed tomography. The authors also evaluated the in vivo tumor targeting in subcutaneously implanted RR1022 rats...
March 2, 2018: Cancer Biotherapy & Radiopharmaceuticals
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