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Bella H V Nguyen, James Kuo, Anadian Budiman, Hayden Christie, Sayed Ali
Immune checkpoint inhibitors have changed the landscape of the treatment of multiple solid malignancies, and have been used increasingly in the recent years. Although usually well tolerated, given the relative inexperience of using immune checkpoint inhibitors, we are still learning of new side effects from the treatment. We report on two cases of ocular myasthenia gravis that occurred after treatment with pembrolizumab, an antiprogrammed-death (anti-PD1) monoclonal antibody for advanced melanoma in responding patients...
October 21, 2016: Melanoma Research
Adewale L Oyeyemi, Terry L Conway, Rufus A Adedoyin, Kingsley K Akinroye, Richmond Aryeetey, Felix Assah, Kelli L Cain, Kavita A Gavand, Sandra S Kasoma, Tracy L Kolbe-Alexander, Estelle V Lambert, Richard Larouche, Sarah J Mos, Reginald Ocansey, Vincent O Onywera, Antonio Prista, Mark S Tremblay, James F Sallis
PURPOSE: Development of valid measures of built environments relevant for physical activity is an important step toward controlling the global epidemic of physical inactivity-related non-communicable diseases and deaths. This study assessed the construct validity of a self-report neighborhood environment walkability scale adapted for Africa (NEWS-Africa), by examining relationships with self-reported walking for transportation and recreation using pooled data from six sub-Saharan African countries...
October 21, 2016: Medicine and Science in Sports and Exercise
Ryan K Robison, Ashley G Anderson, James G Pipe
PURPOSE: Three-dimensional ultrashort echo-time (UTE) imaging commonly makes use of an isotropic 3D radial projection acquisition. The FLORET sequence is proposed and evaluated as a more efficient alternative. METHODS: The properties of the FLORET trajectory are contrasted with those of a 3D radial projection trajectory. The theoretical advantages of FLORET, including greater sampling and SNR efficiency, are evaluated based upon experimental data. The effect of T2* decay on FLORET is analyzed in comparison to the 3D radial, Cones, and Density Adapted Radial trajectories...
October 24, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Pablo Alonso-González, Alexey Y Nikitin, Yuanda Gao, Achim Woessner, Mark B Lundeberg, Alessandro Principi, Nicolò Forcellini, Wenjing Yan, Saül Vélez, Andreas J Huber, Kenji Watanabe, Takashi Taniguchi, Félix Casanova, Luis E Hueso, Marco Polini, James Hone, Frank H L Koppens, Rainer Hillenbrand
Terahertz (THz) fields are widely used for sensing, communication and quality control. In future applications, they could be efficiently confined, enhanced and manipulated well below the classical diffraction limit through the excitation of graphene plasmons (GPs). These possibilities emerge from the strongly reduced GP wavelength, λp, compared with the photon wavelength, λ0, which can be controlled by modulating the carrier density of graphene via electrical gating. Recently, GPs in a graphene/insulator/metal configuration have been predicted to exhibit a linear dispersion (thus called acoustic plasmons) and a further reduced wavelength, implying an improved field confinement, analogous to plasmons in two-dimensional electron gases (2DEGs) near conductive substrates...
October 24, 2016: Nature Nanotechnology
F Lee Cantrell, James Sherrard, Michael Andrade, Bethann Schaber, Iain M McIntyre
BACKGROUND: Death due to prescription opioid exposure has increased dramatically in North America. Currently, there is a lack of literature detailing potentially lethal doses as well as postmortem tissue analysis concentrations from prescription opioid fatalities in children. We report a pediatric hydromorphone fatality with postmortem peripheral blood, central blood, liver, and gastric concentrations. CASE REPORT: A 3-year-old male was found unresponsive on a couch...
October 24, 2016: Clinical Toxicology
Steffen Grampp, James L Platt, Victoria Lauer, Rafik Salama, Franziska Kranz, Viviana K Neumann, Sven Wach, Christine Stöhr, Arndt Hartmann, Kai-Uwe Eckardt, Peter J Ratcliffe, David R Mole, Johannes Schödel
Clear cell renal cell carcinoma (ccRCC) is characterized by loss of function of the von Hippel-Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible transcription factors (HIFs). Genetic and epigenetic determinants have an impact on HIF pathways. A recent genome-wide association study on renal cancer susceptibility identified single-nucleotide polymorphisms (SNPs) in an intergenic region located between the oncogenes MYC and PVT1. Here using assays of chromatin conformation, allele-specific chromatin immunoprecipitation and genome editing, we show that HIF binding to this regulatory element is necessary to trans-activate MYC and PVT1 expression specifically in cells of renal tubular origins...
October 24, 2016: Nature Communications
Athanasios Tsiouris, Lynn Wilson, Rajesh B Sekar, Abeel A Mangi, James J Yun
BACKGROUND: A lack of donor hearts remains a major limitation of heart transplantation. Hearts from Centers for Disease Control (CDC) high-risk donors can be utilized with specific recipient consent. However, outcomes of heart transplantation with CDC high-risk donors are not well known. We sought to define outcomes, including posttransplant hepatitis and human immunodeficiency virus (HIV) status, in recipients of CDC high-risk donor hearts at our institution. METHODS: All heart transplant recipients from August 2010 to December 2014 (n = 74) were reviewed...
October 23, 2016: Journal of Cardiac Surgery
Nghi C Nguyen, Muhammad Shah, Leonard J Appleman, Rahul Parikh, James M Mountz
Background and Purpose. Radium-223 dichloride (Xofigo®, Bayer HealthCare Pharmaceuticals Inc.) is the first α-particle emitter therapeutic agent approved by the FDA, with benefits in overall survival and delay in symptomatic skeletal event for patients with metastatic castrate-resistant prostate cancer (CRPC). Recent post hoc analyses of the phase III ALSYMPCA trial support the previously established safety profile as well as therapeutic effect and clinical outcome of Radium-223. Currently, Radium-223 is approved as a single agent therapy for metastatic CRPC...
2016: International Journal of Molecular Imaging
Christiana Aryee, William K B A Owiredu, James Osei-Yeboah, Ellis Owusu-Dabo, Edwin F Laing, Isaac K Owusu
The surge in prevalence of chronic noncommunicable diseases like hypertension and chronic kidney disease has been linked with modifiable lifestyle practices and increased body fat. This study sought to compare the association between different modifiable lifestyle practices, adiposity indices, renal function parameters, and hypertension as well as the predictive implications for levels of these parameters in target cardiac organ damage among an urban Ghanaian hypertensive population. Using a hospital-based case-control study design, 241 Ghanaian indigenes from the Kumasi metropolis were recruited for this study...
2016: International Journal of Hypertension
Courtney L Huff, Rachel L Morano, James P Herman, Bryan K Yamamoto, Gary A Gudelsky
3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation...
October 20, 2016: Neurotoxicology
James B Kirkbride, Yasir Hameed, Gayatri Ankireddypalli, Konstantinos Ioannidis, Carolyn M Crane, Mukhtar Nasir, Nikolett Kabacs, Antonio Metastasio, Oliver Jenkins, Ashkan Espandian, Styliani Spyridi, Danica Ralevic, Suneetha Siddabattuni, Ben Walden, Adewale Adeoye, Jesus Perez, Peter B Jones
OBJECTIVE: Few studies have characterized the epidemiology of first-episode psychoses in rural or urban settings since the introduction of early intervention psychosis services. To address this, the authors conducted a naturalistic cohort study in England, where such services are well established. METHOD: All new first-episode psychosis cases, 16-35 years old, presenting to early intervention psychosis services in the East of England were identified during 2 million person-years follow-up...
October 24, 2016: American Journal of Psychiatry
Margaret O James, Stephan C Jahn, Guo Zhong, Marci G Smeltz, Zhiwei Hu, Peter W Stacpoole
Dichloroacetate (DCA) has several therapeutic applications based on its pharmacological property of inhibiting pyruvate dehydrogenase kinase. DCA has been used to treat inherited mitochondrial disorders that result in lactic acidosis, as well as pulmonary hypertension and several different solid tumors, the latter through its ability to reverse the Warburg effect in cancer cells and restore aerobic glycolysis. The main clinically limiting toxicity is reversible peripheral neuropathy. Although administration of high doses to rodents can result in liver cancer, there is no evidence that DCA is a human carcinogen...
October 19, 2016: Pharmacology & Therapeutics
Tom Kai Ming Wang, Andrew Woodhead, Tharumenthiran Ramanathan, James Pemberton
BACKGROUND: Nearly half of the patients undergoing coronary artery bypass grafting (CABG) have diabetes. There is mixed data as to whether preoperative (haemoglobin A1c{HbA1c}) and/or perioperative diabetes control is associated with mortality and morbidity after CABG. We reviewed the characteristics and outcomes of diabetic patients undergoing CABG with a focus on HbA1c, perioperative glucose levels and diabetic treatment regimens. METHODS: Diabetic patients undergoing CABG during July 2010 to June 2012 were studied (n=306)...
July 4, 2016: Heart, Lung & Circulation
Thomas Vanicek, Alexandra Kutzelnigg, Cecile Philippe, Helen L Sigurdardottir, Gregory M James, Andreas Hahn, Georg S Kranz, Anna Höflich, Alexander Kautzky, Tatjana Traub-Weidinger, Marcus Hacker, Wolfgang Wadsak, Markus Mitterhauser, Siegfried Kasper, Rupert Lanzenberger
Altered serotonergic neurotransmission has been found to cause impulsive and aggressive behavior, as well as increased motor activity, all exemplifying key symptoms of ADHD. The main objectives of this positron emission tomography (PET) study were to investigate the serotonin transporter binding potential (SERT BPND ) in patients with ADHD and to assess associations of SERT BPND between the brain regions. 25 medication-free patients with ADHD (age ± SD; 32.39 ± 10.15;10 females) without any psychiatric comorbidity and 25 age and sex matched healthy control subjects (33...
October 22, 2016: Human Brain Mapping
James Anaissie, Wayne J G Hellstrom, Faysal A Yafi
The introduction of collagenase Clostridium histolyticum (CCH) as a treatment option for Peyronie's disease (PD), defined as the abnormal formation of collagen on the tunica albuginea of the penis, has provided patients with a promising new conservative therapy. Studies have shown that CCH improves curvature by an average of 17°, and although patient and sexual partner satisfaction is high, the improvement has arguable clinical implications. Similarly, the efficacy and cost of CCH contrasts strongly with more invasive surgical management, and is further limited by rare, but serious, complications and several contraindications...
October 21, 2016: Drugs
Wenyan Xu, Daniel Kool, Derek K O'Flaherty, Ashley Keating, Lauralicia Sacre, Martin Egli, Anne Marietta Noronha, Christopher James Wilds, Linlin Zhao
DNA interstrand cross-links (ICLs) are cytotoxic DNA lesions derived from reactions of DNA with a number of anti-cancer reagents as well as endogenous bifunctional electrophiles. Deciphering the DNA repair mechanisms of ICLs is important for understanding the toxicity of DNA cross-linking agents and for the development of effective chemotherapies. Previous research has focused on ICLs cross-linked with the N7 and N2 atoms of guanine as well as those formed at the N6 atom of adenine; however, little is known about the mutagenicity of O6-dG-derived ICLs...
October 21, 2016: Chemical Research in Toxicology
James Starrett, Shahan Derkarabetian, Marshal Hedin, Robert W Bryson, John E McCormack, Brant C Faircloth
Arachnida is an ancient, diverse, and ecologically important animal group that contains a number of species of interest for medical, agricultural, and engineering applications. Despite their importance, many aspects of the arachnid tree of life remain unresolved, hindering comparative approaches to arachnid biology. Biologists have made considerable efforts to resolve the arachnid phylogeny; yet, limited and challenging morphological characters, as well as a dearth of genetic resources, have hindered progress...
October 21, 2016: Molecular Ecology Resources
Xiangyi Zhang, Gavin O Jones, James L Hedrick, Robert M Waymouth
Ring-opening polymerization of lactones is a versatile approach to generate well-defined functional polyesters. Typical ring-opening catalysts are subject to a trade-off between rate and selectivity. Here we describe an effective catalytic system combining alkoxides with thioureas that catalyses rapid and selective ring-opening polymerizations. Deprotonation of thioureas by sodium, potassium or imidazolium alkoxides generates a hydrogen-bonded alcohol adduct of the thiourea anion (thioimidate). The ring-opening polymerization of L-lactide mediated by these alcohol-bonded thioimidates yields highly isotactic polylactide with fast kinetics and living polymerization behaviour, as evidenced by narrow molecular weight distributions (Mw/Mn < 1...
November 2016: Nature Chemistry
James Raftery, Steve Hanney, Trish Greenhalgh, Matthew Glover, Amanda Blatch-Jones
BACKGROUND: This report reviews approaches and tools for measuring the impact of research programmes, building on, and extending, a 2007 review. OBJECTIVES: (1) To identify the range of theoretical models and empirical approaches for measuring the impact of health research programmes; (2) to develop a taxonomy of models and approaches; (3) to summarise the evidence on the application and use of these models; and (4) to evaluate the different options for the Health Technology Assessment (HTA) programme...
October 2016: Health Technology Assessment: HTA
Meghan B Brennan, Barbara L Herwaldt, James J Kazmierczak, John W Weiss, Christina L Klein, Catherine P Leith, Rong He, Matthew J Oberley, Laura Tonnetti, Patricia P Wilkins, Gregory M Gauthier
Babesia microti, an intraerythrocytic parasite, is tickborne in nature. In contrast to transmission by blood transfusion, which has been well documented, transmission associated with solid organ transplantation has not been reported. We describe parasitologically confirmed cases of babesiosis diagnosed ≈8 weeks posttransplantation in 2 recipients of renal allografts from an organ donor who was multiply transfused on the day he died from traumatic injuries. The organ donor and recipients had no identified risk factors for tickborne infection...
November 2016: Emerging Infectious Diseases
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