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Kristina R Kesely, Antonella Pantaleo, Francesco M Turrini, Peter Olupot-Olupot, Philip S Low
With half of the world's population at risk for malaria infection and with drug resistance on the rise, the search for mutation-resistant therapies has intensified. We report here a therapy for Plasmodium falciparum malaria that acts by inhibiting the phosphorylation of erythrocyte membrane band 3 by an erythrocyte tyrosine kinase. Because tyrosine phosphorylation of band 3 causes a destabilization of the erythrocyte membrane required for parasite egress, inhibition of the erythrocyte tyrosine kinase leads to parasite entrapment and termination of the infection...
2016: PloS One
Philip M P Poortmans, Charlotte Coles, Jacques Bernier
No abstract text is available yet for this article.
October 20, 2016: JAMA Oncology
Michael P Grubb, Philip M Coulter, Hugo J B Marroux, Balazs Hornung, Ryan S McMullen, Andrew J Orr-Ewing, Michael N R Ashfold
Spectroscopically observing the translational and rotational motion of solute molecules in liquid solutions is typically impeded by their interactions with the solvent, which conceal spectral detail through linewidth broadening. Here we show that unique insights into solute dynamics can be made with perfluorinated solvents, which interact weakly with solutes and provide a simplified liquid environment that helps to bridge the gap in our understanding of gas- and liquid-phase dynamics. Specifically, we show that in such solvents, the translational and rotational cooling of an energetic CN radical can be observed directly using ultrafast transient absorption spectroscopy...
November 2016: Nature Chemistry
Jeffrey Cummings, Philip Scheltens, Ian McKeith, Rafael Blesa, John E Harrison, Paulo H F Bertolucci, Kenneth Rockwood, David Wilkinson, Wouter Wijker, David A Bennett, Raj C Shah
BACKGROUND: Souvenaid® (uridine monophosphate, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium), was developed to support the formation and function of neuronal membranes. OBJECTIVE: To determine effect sizes observed in clinical trials of Souvenaid and to calculate the number needed to treat to show benefit or harm. METHODS: Data from all three reported randomized controlled trials of Souvenaid in Alzheimer's disease (AD) dementia (Souvenir I, Souvenir II, and S-Connect) and an open-label extension study were included in analyses of effect size for cognitive, functional, and behavioral outcomes...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Paul M Foreman, Christoph J Griessenauer, Kimberly P Kicielinski, Philip G R Schmalz, Brandon G Rocque, Matthew R Fusco, Joseph C Sullivan, John P Deveikis, Mark R Harrigan
OBJECTIVE Blunt traumatic cerebrovascular injury (TCVI) represents structural injury to a vessel due to high-energy trauma. The Biffl Scale is a widely accepted grading scheme for these injuries that was developed using digital subtraction angiography. In recent years, screening CT angiography (CTA) has been used to identify patients with TCVI. The reliability of this scale, with injuries assessed using CTA, has not yet been determined. METHODS Seven independent raters, including 2 neurosurgeons, 2 neuroradiologists, 2 neurosurgical residents, and 1 neurosurgical vascular fellow, independently reviewed each presenting CTA of the neck performed in 40 patients with confirmed TCVI and assigned a Biffl grade...
October 21, 2016: Journal of Neurosurgery
Gregory F Funston, Philip J Currie, David A Eberth, Michael J Ryan, Tsogtbaatar Chinzorig, Demchig Badamgarav, Nicholas R Longrich
A monodominant bonebed of Avimimus from the Nemegt Formation of Mongolia is the first oviraptorosaur bonebed described and the only recorded maniraptoran bonebed from the Late Cretaceous. Cranial elements recovered from the bonebed provide insights on the anatomy of the facial region, which was formerly unknown in Avimimus. Both adult and subadult material was recovered from the bonebed, but small juveniles are underrepresented. The taphonomic and sedimentological evidence suggests that the Avimimus bonebed represents a perimortem gregarious assemblage...
October 21, 2016: Scientific Reports
Ursula Oestreicher, Daniel Samaga, Elizabeth Ainsbury, Ana Catarina Antunes, Ans Baeyens, Leonardo Barrios, Christina Beinke, Philip Beukes, William F Blakely, Alexandra Cucu, Andrea De Amicis, Julie Depuydt, Stefania De Sanctis, Marina Di Giorgio, Katalin Dobos, Inmaculada Dominguez, Pham Ngoc Duy, Marco E Espinoza, Farrah N Flegal, Markus Figel, Omar Garcia, Octávia Monteiro Gil, Eric Gregoire, C Guerrero-Carbajal, İnci Güçlü, Valeria Hadjidekova, Prakash Hande, Ulrike Kulka, Jennifer Lemon, Carita Lindholm, Florigio Lista, Katalin Lumniczky, Wilner Martinez-Lopez, Nataliya Maznyk, Roberta Meschini, Radia M'kacher, Alegria Montoro, Jayne Moquet, Mercedes Moreno, Mihaela Noditi, Jelena Pajic, Analía Radl, Michelle Ricoul, Horst Romm, Laurence Roy, Laure Sabatier, Natividad Sebastià, Jacobus Slabbert, Sylwester Sommer, Monica Stuck Oliveira, Uma Subramanian, Yumiko Suto, Tran Que, Antonella Testa, Georgia Terzoudi, Anne Vral, Ruth Wilkins, LusiYanti Yanti, Demetre Zafiropoulos, Andrzej Wojcik
PURPOSE: Two quality controlled inter-laboratory exercises were organized within the EU project 'Realizing the European Network of Biodosimetry (RENEB)' to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network. MATERIALS AND METHODS: The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants...
October 21, 2016: International Journal of Radiation Biology
Philip M Massey, Brent A Langellier, Tetine Sentell, Jennifer Manganello
OBJECTIVE: To examine differences in health information seeking between U.S.-born and foreign-born populations in the U.S. DESIGN: Data from 2008 to 2014 from the Health Information National Trends Survey were used in this study (n = 15,249). Bivariate analyses, logistic regression, and predicted probabilities were used to examine health information seeking and sources of health information. RESULTS: Findings demonstrate that 59.3% of the Hispanic foreign-born population reported looking for health information, fewer than other racial/ethnic groups in the sample...
October 21, 2016: Ethnicity & Health
Hahnbeom Park, Philip Bradley, Per Greisen, Yuan Liu, Vikram Khipple Mulligan, David E Kim, David Baker, Frank DiMaio
Most biomolecular modeling energy functions for structure prediction, sequence design, and molecular docking, have been parameterized using existing macromolecular structural data; this contrasts molecular mechanics force fields which are largely optimized using small-molecule data. In this study, we describe an integrated method that enables optimization of a biomolecular modeling energy function simultaneously against small-molecule thermodynamic data and high-resolution macromolecular structural data. We use this approach to develop a next-generation Rosetta energy function that utilizes a new anisotropic implicit solvation model, and an improved electrostatics and Lennard-Jones model, illustrating how energy functions can be considerably improved in their ability to describe large-scale energy landscapes by incorporating both small-molecule and macromolecule data...
October 21, 2016: Journal of Chemical Theory and Computation
Amy Webster, Philip Crea, Mark W Bamford, Roger Hew, Yvette Griffin, Fiona Miall
No abstract text is available yet for this article.
October 21, 2016: British Journal of Haematology
Conor O'Neill, Damian Smith, Martin Caddow, Fergal Duffy, Philip Hickey, Mary Fitzpatrick, Fintan Caddow, Tom Cronin, Mark Joynt, Zetti Azvee, Bronagh Gallagher, Claire Kehoe, Catherine Maddock, Benjamin O'Keeffe, Louise Brennan, Mary Davoren, Elizabeth Owens, Ronan Mullaney, Laurence Keevans, Ronan Maher, Harry G Kennedy
BACKGROUND: People with major mental illness are over-represented in prison populations however there are few longitudinal studies of prison in-reach services leading to appropriate healthcare over extended periods. AIMS: We aimed to examine measures of the clinical efficiency and effectiveness of a prison in-reach, court diversion and liaison service over a 3 year period. Secondly, we aimed to compare rates of identification of psychosis and diversion with rates previously reported for the same setting in the 6 years previously...
2016: International Journal of Mental Health Systems
Matthew Sykes, Natalie A Matheson, Philip W Brownjohn, Alexander D Tang, Jennifer Rodger, Jonathan B H Shemmell, John N J Reynolds
Repetitive transcranial magnetic stimulation (rTMS) is primarily used in humans to change the state of corticospinal excitability. To assess the efficacy of different rTMS stimulation protocols, motor evoked potentials (MEPs) are used as a readout due to their non-invasive nature. Stimulation of the motor cortex produces a response in a targeted muscle, and the amplitude of this twitch provides an indirect measure of the current state of the cortex. When applied to the motor cortex, rTMS can alter MEP amplitude, however, results are variable between participants and across studies...
2016: Frontiers in Neural Circuits
H H Yoon, J C Bendell, F S Braiteh, I Firdaus, P A Philip, A L Cohn, N Lewis, D M Anderson, E Arrowsmith, J D Schwartz, L Gao, Y Hsu, Y Xu, D Ferry, S R Alberts, Z A Wainberg
BACKGROUND: We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ). PATIENTS AND METHODS: Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks...
October 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Felipe B Schuch, Davy Vancampfort, Xuemei Sui, Simon Rosenbaum, Joseph Firth, Justin Richards, Philip B Ward, Brendon Stubbs
Physical activity (PA) is protective from future depression, however, the potential impact of cardiorespiratory fitness (CRF) on the development of depression is less clear. We aimed to investigate if lower levels of CRF are associated with a higher risk for depression onset. Major electronic databases were searched, from inception to January 2016 for prospective cohort studies evaluating the association between CRF and incident depression. Pooled hazard ratio (HR) with 95% confidence intervals (CIs) were calculated...
October 17, 2016: Preventive Medicine
Rick Morrison, Zhaohua Zheng, Ian G Jennings, Philip E Thompson, Jasim M A Al-Rawi
To continue our study of 2-morpholino-benzoxazine based compounds, which show useful activity against PI3K family enzymes or antiplatelet activity, we designed and synthesized a series of linear 6.7-fused, 5,6-angular fused and 7,8-angular fused-aryl-morpholino-naphth-oxazines. The compounds were prepared from substituted 2-hydroxynaphthoic acid to give the corresponding thioxo analogues 8, 9, 15 and 19. The thioxo products were then converted to the morpholino substituted analogue. The aryl group was introduced by Suzuki coupling of bromo precursors...
October 5, 2016: Bioorganic & Medicinal Chemistry Letters
Suzanne V Arnold, Jonathan Afilalo, John A Spertus, Yuanyuan Tang, Suzanne J Baron, Philip G Jones, Michael J Reardon, Steven J Yakubov, David H Adams, David J Cohen
BACKGROUND: A series of models have been developed to identify patients at high risk for poor outcomes after transcatheter aortic valve replacement (TAVR) to help guide treatment choices, offer patients realistic expectations of long-term outcomes, and support decision making. OBJECTIVES: This study examined the performance of the previously developed TAVR Poor Outcome risk models in an external dataset and explored the incremental contribution of geriatric domains to model performance...
October 25, 2016: Journal of the American College of Cardiology
Elisabeth Waldmann, Georg Heinze, Arnulf Ferlitsch, Irina GessI, Daniela Sallinger, Philip Jeschek, Martha Britto-Arias, Petra Salzl, Elisabeth Fasching, Bernd Jilma, Michael Kundi, Michael Trauner, Monika Ferlitsch
BACKGROUND: Prevalence of (pre)cancerous colorectal lesions are higher in men than in women, although transition rates from advanced lesions to cancer is similar in both sexes. Our aim was to investigate whether the sex-specific difference in incidence of premalignant colorectal lesions might be explained by the impact of risk factors. METHODS: A cross-sectional study analysing health check-up examinations and screening colonoscopies performed within a national quality assurance program...
October 20, 2016: British Journal of Cancer
Rodrigo Hagemann, Vanessa Dos Santos Silva, Fábio Cardoso Carvalho, Pasqual Barretti, Luis Cuadrado Martin, Diana Vassallo, Philip A Kalra, Roberto Jorge da Silva Franco
BACKGROUND: To date, renal revascularization has not been shown to be advantageous when compared to optimized medical treatment in patients with atheromatous renovascular disease (ARVD). This study aims to investigate the effect of revascularization in patients with pre-intervention worsening renal function and in those with stable renal function. PATIENTS AND METHODS: In this single-centre observational study, patients who were diagnosed with at least 60% angiographic stenosis unilaterally or bilaterally between January 1996 and October 2008 and who were followed-up until February 2011 were retrospectively analysed...
October 21, 2016: Nephron
Vivek Subbiah, Oliver Holmes, Kyle Gowen, Daniel Spritz, Behrang Amini, Wei-Lien Wang, Alexa B Schrock, Funda Meric-Bernstam, Ralph Zinner, Sarina Piha-Paul, Maria Zarzour, Julia A Elvin, Rachel L Erlich, David L Stockman, Jo-Anne Vergilio, James H Suh, Philip J Stephens, Vincent Miller, Jeffrey S Ross, Siraj M Ali
Malignant gastrointestinal neuroectodermal tumor (GNET) is an aggressive rare tumor, primarily occurring in young adults with frequent local-regional metastases and recurrence after local control. The tumor is characterized by the presence of EWSR1-ATF1 or EWSR1-CREB1 and immunohistochemical positivity for S-100 protein without melanocytic marker positivity. Due to poor responses to standard sarcoma regimens, GNET has a poor prognosis, and development of effective systemic therapy is desperately needed to treat these patients...
October 21, 2016: Oncology
Uday B Maachani, Uma Shankavaram, Tamalee Kramp, Philip J Tofilon, Kevin Camphausen, Anita T Tandle
Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo...
October 14, 2016: Oncotarget
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