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Emmanuel Boulay, Michael K Pugsley, Vincent Jacquemet, Alain Vinet, Michael V Accardi, Maxim Soloviev, Eric Troncy, Jennifer M Doyle, Jennifer Beck Pierson, Simon Authier
INTRODUCTION: QT has a long history of heart rate (HR) correction but limited investigations have been undertaken to assess the impact of cardiovascular parameters on left ventricular (LV) contractility in drug safety testing. Cardiac contractility is affected by preload (Cyon-Frank-Starling law), afterload (Anrep effect) and HR (Bowditch effect). We evaluated multi-parameter correction methods to help with dP/dtmax interpretation. METHODOLOGY: Modeling was undertaken using data from dogs in single or double 4×4 Latin square studies...
April 20, 2017: Journal of Pharmacological and Toxicological Methods
Julie E Twidwell, Kathie Records
Nursing programs reject qualified applicants due to limited clinical placements and faculty. By admitting the strongest candidates, schools of nursing will reduce attrition rates, increase NCLEX-RN pass rates, and speed the entry into practice of well-prepared nurses to help stem the nursing shortage. This integrative review identified the standardized admission exams most predictive of student success. Included were articles published between 2005 and 2016 that focused on admission criteria, RN programs, specific exams (e...
April 1, 2017: International Journal of Nursing Education Scholarship
D Zacs, V Bartkevics
An analytical method was established and validated for the analysis of the most frequently monitored representatives among the group of perfluorinated compounds (PFAS), namely, perfluorooctanoic acid (PFOA) and prefluorooctane sulfonate (PFOS) in environmental samples (surface water, wastewater, sediments, sewage sludge, and biota). High performance liquid chromatography (HPLC) coupled to Orbitrap mass spectrometry (Orbitrap-MS) employing a heated electrospray ionization (HESI) interface operated in negative mode was used for the quantitative determination of these contaminants...
November 18, 2016: Journal of Chromatography. A
M Dellarco, R Zaleski, B J Gaborek, H Qian, C A Bellin, P Egeghy, N Heard, O Jolliet, D R Lander, N Sunger, K S Stylianou, J Y Tanir
The ILSI Health and Environmental Sciences Institute (HESI) Risk Assessment in the Twenty-first Century (RISK21) project was initiated to address and catalyze improvements in human health risk assessment. RISK21 is a problem formulation-based conceptual roadmap and risk matrix visualization tool, facilitating transparent evaluation of both hazard and exposure components. The RISK21 roadmap is exposure-driven, that is, exposure is used as the second step (after problem formulation) to define and focus the assessment...
February 10, 2017: Critical Reviews in Toxicology
Randy W Purves, Satendra Prasad, Michael Belford, Albert Vandenberg, Jean-Jacques Dunyach
The implementation of an aerodynamic mechanism to improve ion sampling between nanoelectrospray (n-ESI) and FAIMS was recently reported for proteomic analyses. This investigation explores the new FAIMS interface for small molecule analysis at high liquid flow rates and includes an examination of key differences in ionization between heated-ESI (HESI) and n-ESI. The sheath gas, critical for desolvation with HESI, affects FAIMS operation as higher FAIMS gas flow rates are required to achieve sufficient desolvation...
January 17, 2017: Journal of the American Society for Mass Spectrometry
Noemi D Paguigan, Tamam El-Elimat, Diana Kao, Huzefa A Raja, Cedric J Pearce, Nicholas H Oberlies
Effective and rapid dereplication is a hallmark of present-day drug discovery from natural sources. This project strove to both decrease the time and expand the structural diversity associated with dereplication methodologies. A 5 min liquid chromatographic run time employing heated electrospray ionization (HESI) was evaluated to determine whether it could be used as a faster alternative over the 10 min ESI method we reported previously. Results revealed that the 5 min method was as sensitive as the 10 min method and, obviously, was twice as fast...
May 2017: Journal of Antibiotics
Alexia Grangeon, Sophie Gravel, Fleur Gaudette, Jacques Turgeon, Veronique Michaud
Cocktails composed of several Cytochrome P450 (CYP450)-selective probe drugs have been shown of value to characterize in vivo drug-metabolism activities. Our objective was to develop and validate highly sensitive and selective LC-MS/MS assays allowing the determination of seven major human CYP450 isoenzyme activities following administration of low oral doses of a modified CYP450 probe-drug cocktail in patients. The seven-drug cocktail was composed of caffeine, bupropion, tolbutamide, omeprazole, dextromethorphan, midazolam (all administered concomitantly) and chlorzoxazone (administered separately) to phenotype for CYP1A2, 2B6, 2C9, 2C19, 2D6, 3A4/5 and 2E1, respectively...
January 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Eun-Jung Shim, Hong Jin Jeon, Hana Kim, Kwang-Min Lee, Dooyoung Jung, Hae-Lim Noh, Myoung-Sun Roh, Bong-Jin Hahm
BACKGROUND: Medical students face a variety of stressors associated with their education; if not promptly identified and adequately dealt with, it may bring about several negative consequences in terms of mental health and academic performance. This study examined psychometric properties of the Korean version of the Higher Education Stress Inventory (K-HESI). METHODS: The reliability and validity of the K-HESI were examined in a large scale multi-site survey involving 7110 medical students...
November 24, 2016: BMC Medical Education
A G Tecleab, R C Schofield, L V Ramanathan, Dean C Carlow
A simple and sensitive method for the detection of methylmalonic acid in serum without derivatization has been developed. This method implements protein precipitation using methanol followed by additional sample clean up by turbulent flow liquid chromatography (TFLC). The sample was directly injected into the turbulent flow liquid chromatography tandem mass spectrometry system (TFLC-MS/MS) for online extraction followed by HPLC separation. The eluent was transferred to the mass spectrometer and ionized by heated electrospray negative ionization (HESI) and the analyte was quantified using a six-point calibration curve...
October 2016: Journal of Chromatography & Separation Techniques
Thierry Dagnac, Alicia Latorre, Bruno Fernández Lorenzo, Maria Llompart
The first objective of this study was the validation of an efficient multi-analyte method for the simultaneous detection and quantification of mycotoxins in maize silage, by reverse-phase liquid chromatography coupled with electrospray ionisation triple quadrupole mass spectrometry (LC-HESI-MS/MS). A simple liquid/solid extraction was performed either with clean-up on Mycospin 400 columns or without any clean-up. Almost all the target mycotoxins showed highly-suppressed signals in the presence of a matrix, emphasising the need to quantitate mycotoxins by means of matrix-matched calibrations...
December 2016: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
E Lorge, M M Moore, J Clements, M O'Donovan, M D Fellows, M Honma, A Kohara, S Galloway, M J Armstrong, V Thybaud, B Gollapudi, M J Aardema, J Y Tanir
Good cell culture practice and characterization of the cell lines used are of critical importance in in vitro genotoxicity testing. The objective of this initiative was to make continuously available stocks of the characterized isolates of the most frequently used mammalian cell lines in genotoxicity testing anywhere in the world ('IVGT' cell lines). This project was organized under the auspices of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing...
October 2016: Mutation Research
Angelo Moretto, Ammie Bachman, Alan Boobis, Keith R Solomon, Timothy P Pastoor, Martin F Wilks, Michelle R Embry
The ILSI Health and Environmental Sciences Institute (HESI) has developed a framework to support a transition in the way in which information for chemical risk assessment is obtained and used (RISK21). The approach is based on detailed problem formulation, where exposure drives the data acquisition process in order to enable informed decision-making on human health safety as soon as sufficient evidence is available. Information is evaluated in a transparent and consistent way with the aim of optimizing available resources...
February 2017: Critical Reviews in Toxicology
Keith R Solomon, Martin F Wilks, Ammie Bachman, Alan Boobis, Angelo Moretto, Timothy P Pastoor, Richard Phillips, Michelle R Embry
When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors...
November 2016: Critical Reviews in Toxicology
G Astrid Garzón, Carlos-Eduardo Narváez-Cuenca, Jean-Paul Vincken, Harry Gruppen
Berries of Colombian Euterpe oleracea Mart. were analyzed for total phenolic content (TPC), anthocyanin (ACN) content, and antioxidant activity. Additionally, reversed-phase ultra-high performance liquid chromatography with photodiode array detection (RP-UHPLC-PDA) and heated electrospray ionization (HESI) multistage mass spectrometry (MS(n)) were used to determine the composition of phenolic compounds. Anthocyanin content was 0.57±0.39mg cyanidin-3-glucoside/g fresh weight (FW) and TPC was 6.07±2.17mg gallic acid equivalent (GAE)/g FW...
February 15, 2017: Food Chemistry
Kerry L Dearfield, B Bhaskar Gollapudi, Jeffrey C Bemis, R Daniel Benz, George R Douglas, Rosalie K Elespuru, George E Johnson, David J Kirkland, Matthew J LeBaron, Albert P Li, Francesco Marchetti, Lynn H Pottenger, Emiel Rorije, Jennifer Y Tanir, Veronique Thybaud, Jan van Benthem, Carole L Yauk, Errol Zeiger, Mirjam Luijten
For several decades, regulatory testing schemes for genetic damage have been standardized where the tests being utilized examined mutations and structural and numerical chromosomal damage. This has served the genetic toxicity community well when most of the substances being tested were amenable to such assays. The outcome from this testing is usually a dichotomous (yes/no) evaluation of test results, and in many instances, the information is only used to determine whether a substance has carcinogenic potential or not...
September 21, 2016: Environmental and Molecular Mutagenesis
Liselotte Tinel, Stéphanie Rossignol, Angelica Bianco, Monica Passananti, Sébastien Perrier, Xinming Wang, Marcello Brigante, D James Donaldson, Christian George
Interfaces are ubiquitous in the environment and many atmospheric key processes, such as gas deposition, aerosol, and cloud formation are, at one stage or another, strongly impacted by physical and chemical processes occurring at interfaces. Here, the photoinduced chemistry of an air/water interface coated with nonanoic acid-a fatty acid surfactant we use as a proxy for chemically complex natural aqueous surface microlayers-was investigated as a source of volatile and semivolatile reactive organic species. The carboxylic acid coating significantly increased the propensity of photosensitizers, chosen to mimic those observed in real environmental waters, to partition to the interface and enhance reactivity there...
October 18, 2016: Environmental Science & Technology
Karol L Thompson, Eric Boitier, Tao Chen, Philippe Couttet, Heidrun Ellinger-Ziegelbauer, Manuela Goetschy, Gregory Guillemain, Masayuki Kanki, Janet Kelsall, Claire Mariet, Catherine de La Moureyre-Spire, Peter Mouritzen, Rounak Nassipour, Raegan O'Lone, P Scott Pine, Barry A Rosenzweig, Tatiana Sharapova, Aaron Smith, Hidefumi Uchiyama, Jian Yan, Peter S Yuen, Russ Wolfinger
Extracellular microRNAs (miRNAs) represent a promising new source of toxicity biomarkers that are sensitive indicators of site of tissue injury. In order to establish reliable approaches for use in biomarker validation studies, the HESI technical committee on genomics initiated a multi-site study to assess sources of variance associated with quantitating levels of cardiac injury induced miRNAs in biofluids using RT-qPCR. Samples were generated at a central site using a model of acute cardiac injury induced in male Wistar rats by 0...
September 7, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Shanoy C Anderson, Seenivasan Subbiah, Angella Gentles, Galen Austin, Paul Stonum, Tiffanie A Brooks, Chance Brooks, Ernest E Smith
A method for confirmation and detection of Florfenicol amine residues in white-tailed deer tissues was developed and validated in our laboratory. Tissue samples were extracted with ethyl acetate and cleaned up on sorbent (Chem-elut) cartridges. Liguid chromatography (LC) separation was achieved on a Zorbax Eclipse plus C18 column with gradient elution using a mobile phase composed of ammonium acetate in water and methanol at a flow rate of 300μL/min. Qualitative and quantitative analyses were carried out using liquid chromatography - heated electrospray ionization(HESI) and atmospheric pressure chemical ionization (APCI)-tandem mass spectrometry in the multiple reaction monitoring (MRM) interface...
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Christine Grimaldi, Deborah Finco, Madeline M Fort, Daniel Gliddon, Kirsty Harper, Whitney S Helms, Jane A Mitchell, Raegan O'Lone, Stanley T Parish, Marie-Soleil Piche, Daniel M Reed, Gabriele Reichmann, Patricia C Ryan, Richard Stebbings, Mindi Walker
In October 2013, the International Life Sciences Institute - Health and Environmental Sciences Institute Immunotoxicology Technical Committee (ILSI-HESI ITC) held a one-day workshop entitled, "Workshop on Cytokine Release: State-of-the-Science, Current Challenges and Future Directions". The workshop brought together scientists from pharmaceutical, academic, health authority, and contract research organizations to discuss novel approaches and current challenges for the use of in vitro cytokine release assays (CRAs) for the identification of cytokine release syndrome (CRS) potential of novel monoclonal antibody (mAb) therapeutics...
September 2016: Cytokine
Thomas Colatsky, Bernard Fermini, Gary Gintant, Jennifer B Pierson, Philip Sager, Yuko Sekino, David G Strauss, Norman Stockbridge
The implementation of the ICH S7B and E14 guidelines has been successful in preventing the introduction of potentially torsadogenic drugs to the market, but it has also unduly constrained drug development by focusing on hERG block and QT prolongation as essential determinants of proarrhythmia risk. The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative was established to develop a new paradigm for assessing proarrhythmic risk, building on the emergence of new technologies and an expanded understanding of torsadogenic mechanisms beyond hERG block...
September 2016: Journal of Pharmacological and Toxicological Methods
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