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Precision 2.0

N D Yeomans, D Y Graham, M E Husni, D H Solomon, T Stevens, J Vargo, Q Wang, L M Wisniewski, K E Wolski, J S Borer, P Libby, A M Lincoff, T F Lüscher, W Bao, C Walker, S E Nissen
BACKGROUND: We evaluated GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety. METHODS: This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed...
April 17, 2018: Alimentary Pharmacology & Therapeutics
Itu Singh, Asha Ram Yadav, Keshar Kunja Mohanty, Kiran Katoch, Prashant Sharma, Vinay Kumar Pathak, Deepa Bisht, Umesh D Gupta, Utpal Sengupta
Background: It has been shown earlier that there is a rise in the levels of autoantibodies and T cell response to cytoskeletal proteins in leprosy. Our group recently demonstrated a rise in both T and B cell responses to keratin and myelin basic protein in all types of leprosy patients and their associations in type 1 reaction (T1R) group of leprosy. Objectives: In this study, we investigated the association of levels of autoantibodies and lymphoproliferation against myosin in leprosy patients across the spectrum and tried to find out the mimicking proteins or epitopes between host protein and protein/s of Mycobacterium leprae ...
2018: Frontiers in Immunology
Yufei Wang, Wei Peng, Junling Tang, Lu Dong, Chengchen Gu, Xin Zhang, Jian Zhou, Weiping Jia
Introduction: A real world clinical study was designed and conducted to evaluate the performance of a novel point-of-care device for determination of glycated haemoglobin A1c (HbA1c ), A1C EZ 2.0, in daily clinical practice. Materials and methods: Five hundred and fourteen subjects were included in this study, and divided into three groups. HbA1c was measured by A1C EZ 2.0 and three different high performance liquid chromatography (HPLC) devices: Bio-Rad Variant II Turbo, Tosoh HLC-723 G8 and Premier Hb9210 separately...
June 15, 2018: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
Erin C O'Neil, Jiayan Huang, Eric B Suhler, James P Dunn, Victor L Perez, David C Gritz, Kathy McWilliams, Ellen Peskin, Gui-Shuang Ying, Vatinee Y Bunya, Maureen G Maguire, John H Kempen
Currently available treatment options for non-infectious scleritis, including non-steroidal anti-inflammatory drugs, systemic corticosteroids and immunosuppressive therapies, have both efficacy and side effect limitations. Iontophoretic delivery of corticosteroids has been demonstrated to be effective for anterior uveitis and represents a potential new approach to scleritis therapy. We hypothesised that iontophoretic delivery would provide effective and precise medication delivery to the sclera, while limiting systemic exposure and side effects...
April 17, 2018: British Journal of Ophthalmology
Luke C Mullany, Elburg W van Boetzelaer, Julie R Gutman, Laura C Steinhardt, Pascal Ngoy, Yolanda Barbera Lainez, Alison Wittcoff, Steven A Harvey, Lara S Ho
BACKGROUND: The World Health Organization's integrated community case management (iCCM) guidelines recommend that all children presenting with uncomplicated fever and no danger signs return for follow-up on day 3 following the initial consultation on day 1. Such fevers often resolve rapidly, however, and previous studies suggest that expectant home care for uncomplicated fever can be safely recommended. We aimed to determine if a conditional follow-up visit was non-inferior to a universal follow-up visit for these children...
April 2018: PLoS Medicine
Steven M Brunwasser, Tebeb Gebretsadik, Diane R Gold, Kedir N Turi, Cosby A Stone, Soma Datta, James E Gern, Tina V Hartert
BACKGROUND: The International Study of Asthma and Allergies in Children (ISAAC) Wheezing Module is commonly used to characterize pediatric asthma in epidemiological studies, including nearly all airway cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) consortium. However, there is no consensus model for operationalizing wheezing severity with this instrument in explanatory research studies. Severity is typically measured using coarsely-defined categorical variables, reducing power and potentially underestimating etiological associations...
2018: PloS One
Jincheng Yang, Maulik Patel, Mina Nikanjam, Edmund V Capparelli, Shirley M Tsunoda, Howard E Greenberg, Scott R Penzak, S Aubrey Stoch, Joseph S Bertino, Anne N Nafziger, Joseph D Ma
Midazolam is the preferred probe to phenotype cytochrome P450 (CYP) 3A activity. This study evaluated a single-concentration, midazolam limited sampling strategy utilizing a population pharmacokinetic (PK) approach to estimate area under the curve, and thus CYP3A activity. Midazolam concentrations from adults during CYP3A constitutive conditions were obtained from previous studies after single, oral or intravenous administration. Population PK modeling was conducted by nonlinear mixed-effects modeling. Potential covariates of clearance, volume of distribution, and bioavailability were evaluated...
April 17, 2018: Journal of Clinical Pharmacology
Ling Li, Jing Long, Long Li, Huijuan Cao, Tingting Tang, Xinghua Xi, Ling Qin, Yuxiao Lai, Xinluan Wang
Background/Objective: A novel porous scaffold poly (lactide- co -glycolide) and tricalcium phosphate (PLGA/TCP) was developed by three-dimensional printing technology for bone defect repair. As a Class 2 solvent with less severe toxicity, content of residual 1,4-dioxane in this newly developed scaffold should be rigorously controlled when it is translated to clinical use. In this study, a headspace gas chromatography-mass spectrometric (HS-GC-MS) method and related testing protocol were developed for quantitative determination of 1,4-dioxane in the PLGA/TCP composite scaffolds...
April 2018: Journal of Orthopaedic Translation
Ovidiu C Andronesi, Isabel C Arrillaga-Romany, K Ina Ly, Wolfgang Bogner, Eva M Ratai, Kara Reitz, A John Iafrate, Jorg Dietrich, Elizabeth R Gerstner, Andrew S Chi, Bruce R Rosen, Patrick Y Wen, Daniel P Cahill, Tracy T Batchelor
Inhibitors of the mutant isocitrate dehydrogenase 1 (IDH1) entered recently in clinical trials for glioma treatment. Mutant IDH1 produces high levels of 2-hydroxyglurate (2HG), thought to initiate oncogenesis through epigenetic modifications of gene expression. In this study, we show the initial evidence of the pharmacodynamics of a new mutant IDH1 inhibitor in glioma patients, using non-invasive 3D MR spectroscopic imaging of 2HG. Our results from a Phase 1 clinical trial indicate a rapid decrease of 2HG levels by 70% (CI 13%, P = 0...
April 16, 2018: Nature Communications
Chenning Zhang, Caibin Qin, Guangyi Yang, Fadia Boughaba, Yue He, Weidong Ma, Yonghong Zhang, Song Gao
Maoecrystal A (MC-A) is an ent-kaurane-type diterpene isolated from Rabdosia eriocalyx (Dunn) Hara. MC-A has been reported to show different types of pharmacological activities, including anticancer, anti-inflammatory and bacteriostatic functions. However, bioanalysis of MC-A has not been reported. The purpose of this study is to develop an UPLC-MS/MS method to quantify MC-A in plasma and determine its pharmacokinetic properties using an animal model. The separation was performed using a Waters HSS T3 column (50 mm × 2...
April 10, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Iqbal Ahmad, Muhammad Furqan Mobeen, Muhammad Ali Sheraz, Sofia Ahmed, Zubair Anwar, Ruby Saeed Shaikh, Imtiaz Hussain, Saiyed Muhammad Ali
The photodegradation of ascorbic acid (AH2 ) in the presence of nicotinamide (NA) at pH 2.0-12.0 has been studied using a 30 W UV radiation source. The reaction follows first-order kinetics and the values of apparent first-order rate constants (kobs ) at 1 × 10-3  M NA concentration range from 1.17 (pH 2.0) to 3.61 × 10-3  min-1 (pH 12.0). The values of these rate constants (k0 ) in the absence of NA range from 0.50 (pH 2.0) to 1.75 × 10-3  min-1 (pH 12.0), indicating that the values of kobs for the photodegradation of AH2 in the presence of NA are about 2 fold compared to those of the AH2 alone...
April 8, 2018: Journal of Photochemistry and Photobiology. B, Biology
Yinxian Yang, Hailing Gao, Shanshan Hou, Ruijuan Su, Hongzh Uo Liu, Jin Sun
A quick and sensitive supercritical fluid chromatography with tandem mass spectrometry method for the simultaneous determination of lumefantrine, artemether and its active metabolite dihydroartemisinin in rat plasma was developed and validated. The chromatographic separation was performed on an ACQUITY UPC2 ™ BEH 2-EP column within 2.5 min by gradient elution using compressed CO2 and methanol containing 2 mM ammonium acetate as the mobile phases. Detection was achieved by multiple reaction monitoring using electrospray ionization in the positive ionization mode...
April 16, 2018: Journal of Separation Science
Hao Guo, Junwei Wang, Yuhong Wu, Wenwen Liu, Juan Bu, Qingbiao Zhao
A sensitive and rapid method for the simultaneous determination of nine anticoagulant rodenticides (ARs) in human blood is reported herein. The method involves phospholipid removal pretreatment for reduced matrix effect (ME) and detection with ultra-performance liquid chromatography coupled with tandem mass spectrometry. Satisfactory recoveries were achieved ranging from 80.6% to 113.1% for the nine analytes, with the intra-day relative standard deviations (RSDs) in the range of 3.4-7.9% and inter-day RSDs in the range of 4...
April 5, 2018: Journal of Analytical Toxicology
Aline Dubos, Hamid Meziane, Giovanni Iacono, Aurore Curie, Fabrice Riet, Christelle Martin, Nadège Loaëc, Marie-Christine Birling, Mohammed Selloum, Elisabeth Normand, Guillaume Pavlovic, Tania Sorg, Henk G Stunnenberg, Jamel Chelly, Yann Humeau, Gaëlle Friocourt, Yann Hérault
The Aristaless-related homeobox (ARX) transcription factor is involved in the development of GABAergic and cholinergic neurons in the forebrain. ARX mutations have been associated with a wide spectrum of neurodevelopmental disorders in humans, among which the most frequent, a 24bp duplication in the polyalanine tract 2 (c.428_451dup24), gives rise to intellectual disability, fine motor defects with or without epilepsy. To understand the functional consequences of this mutation, we generated a partially humanized mouse model carrying the c...
April 5, 2018: Human Molecular Genetics
Itamar Loewenstein, Michaella Goldstein, Joseph Moisseiev, Elad Moisseiev
PURPOSE: To evaluate the accuracy and precision of anti-vascular endothelial growth factor volume delivery by intravitreal injections in the clinical setup. METHODS: Volume output was measured in 669 intravitreal injections administered to patients, calculated from the difference in syringe weight before and after expelling the drug. Three groups were included: prefilled bevacizumab 1.0 mL syringe (Group 1, n = 432), pre-filled ranibizumab in a small-volume syringe with low dead-space plunger design (Group 2, n = 125), and aflibercept drawn and injected using a 1...
April 13, 2018: Retina
Nirupama S Wijesuriya, Laura Gainche, Amy S Jordan, David J Berlowitz, Mariannick LeGuen, Peter D Rochford, Fergal J O'Donoghue, Warren R Ruehland, Jayne C Carberry, Jane E Butler, Danny J Eckert
More than 60% of people with tetraplegia have obstructive sleep apnoea (OSA). However, the specific causes are unknown. Genioglossus, the largest upper-airway dilator muscle, is important in maintaining upper-airway patency. Impaired genioglossus muscle function following spinal cord injury may contribute to OSA. This study aimed to determine if genioglossus reflex responses to negative upper-airway pressure are altered in people with OSA and tetraplegia compared to non-neurologically impaired able-bodied individuals with OSA...
April 15, 2018: Journal of Physiology
Antonis Matakos, James M Balter, Yue Cao
We developed an optimized and robust method to estimate liver B0 field inhomogeneity for monitoring and correcting susceptibility-induced geometric distortion in magnetic resonance images for precision therapy. A triple-gradient-echo acquisition was optimized for the whole liver B0 field estimation within a single-exhale breath-hold scan on a 3 T scanner. To eliminate chemical-shift artifacts, fat signals were chosen in-phase between 2 echoes with an echo time difference (ΔTE) of 2.3 milliseconds. To avoid phase-wrapping, other 2 echoes provided a large field dynamic range (1/ΔTE) to cover the B0 field inhomogeneity...
June 2017: Tomography: a Journal for Imaging Research
Andre Granger, Ornella Bricoune, Tina Rajnauth, David Kimball, Heather Kimball, R Shane Tubbs, Marios Loukas
The anterolateral triangle is one of 10 surgical triangles of the cavernous sinus and serves as an important anatomic landmark for the skull base surgeon. There are few studies in the English literature that have precisely defined and measured the borders of the anterolateral triangle and little agreement has been made regarding the nomenclature within the English literature. A total of 12 midsagittally hemisected adult human cadaveric head halves were dissected to expose the anterolateral triangle. The triangle was defined and measurements of the anterior, posterior, and lateral borders were taken...
February 12, 2018: Curēus
Pengfei Zhao, Jing Zhao, Shuo Lei, Xingjie Guo, Longshan Zhao
A rapid and sensitive multi-residue method was developed for the simultaneous quantification of eight chiral pesticides (including diniconazole, metalaxyl, paclobutrazol, epoxiconazole, myclobutanil, hexaconazole, napropamide and isocarbophos) at enantiomeric levels in environmental soils and sediments using chiral liquid chromatography-tandem mass spectrometry based on a combined pretreatment of matrix solid-phase dispersion and dispersive liquid-liquid microextraction (MSPD-DLLME). Under optimized conditions, 0...
April 3, 2018: Chemosphere
O Morgan Hall, Cody J Peer, Courtney D Fitzhugh, William D Figg
Analysis of cyclophosphamide (CP) and its metabolite, 4-hydroxycyclophosphamide (4OHCP), in a single assay has the ability to improve sampling techniques benefitting both the patients who are receiving the drug and the clinicians drawing samples. Due to instability in plasma (t1/2  = 4 min), immediate stabilization of 4OHCP with phenylhydrazine is necessary upon sample draw. After stabilization, 4OHCP and the stable CP prodrug concentrations can be analytically measured to elucidate the pharmacokinetics, including half-life and exposure parameters (Cmax and AUC)...
April 10, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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