FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Piccardo, P Cervenak, J Bu, M Miller, L Asher, DM AF Piccardo, Pedro Cervenak, Juraj Bu, Ming Miller, Lindsay Asher, David M. TI Complex proteinopathy with accumulations of prion protein, hyperphosphorylated tau, alpha-synuclein and ubiquitin in experimental bovine spongiform encephalopathy of monkeys SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; STRAUSSLER-SCHEINKER DISEASE; ARGYROPHILIC GRAIN DISEASE; NEUROFIBRILLARY TANGLES; ALZHEIMER-DISEASE; CEREBROSPINAL-FLUID; SQUIRREL-MONKEYS; SAIMIRI-SCIUREUS; AMYLOID-BETA; VARIANT AB Proteins aggregate in several slowly progressive neurodegenerative diseases called 'proteinopathies'. Studies with cell cultures and transgenic mice overexpressing mutated proteins suggested that aggregates of one protein induced misfolding and aggregation of other proteins as well - a possible common mechanism for some neurodegenerative diseases. However, most proteinopathies are 'sporadic', without gene mutation or overexpression. Thus, proteinopathies in WT animals genetically close to humans might be informative. Squirrel monkeys infected with the classical. bovine spongiform encephalopathy agent developed an encephalopathy resembling variant Creutzfeldt Jakob disease with accumulations not only of abnormal prion protein (PrPTSE), but also three other proteins: hyperphosphorylated tau (p-tau), alpha-synuclein and ubiquitin; beta-amyloid protein (A beta) did not accumulate. Severity of brain lesions correlated with spongiform degeneration. No amyloid was detected. These results suggested that PrPTSE enhanced formation of p-tau and aggregation of alpha-synuclein and ubiquitin, but not A beta, providing a new experimental model for neurodegenerative diseases associated with complex proteinopathies. C1 [Piccardo, Pedro; Cervenak, Juraj; Bu, Ming; Miller, Lindsay; Asher, David M.] US FDA, Lab Bacterial & TSE Agents, Div Emerging Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Piccardo, P (reprint author), US FDA, Lab Bacterial & TSE Agents, Div Emerging Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 313, Rockville, MD 20852 USA. EM pedro.piccardo@fda.hhs.gov FU NIH-NIAID [Y1-AI-4893-02]; Food and Drug Administration (FDA) [224-05-1307] FX We thank Drs Dagmar Heim (Federal Veterinary Office, Bern, Switzerland) and Torsten Seuberlich (NeuroCentre, National and OIE Reference Laboratories for BSE and Scrapie, Vetsuisse Faculty, University of Bern, Bern, Switzerland) for providing the BSE inoculum, and Steve Harbaugh and Jeff Harbaugh (Bioqual, Rockville, MD, USA) for dedicated care of animals. This work was funded by NIH-NIAID agreement no. Y1-AI-4893-02 with the Food and Drug Administration (FDA; agreement no. 224-05-1307): Potential of Candidate Cell Substrates for Vaccine Production to Propagate the Agents of Transmissible Spongiform Encephalopathies (Main Agreement Title: Assessing Safety of Cell Substrates and Vaccine Components). The findings and conclusions in this paper have not been formally disseminated by the FDA and should not be construed to represent any Agency determination or policy. NR 50 TC 2 Z9 2 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD JUL PY 2014 VL 95 BP 1612 EP 1618 DI 10.1099/vir.0.062083-0 PN 7 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA AO2QW UT WOS:000341171300022 PM 24769839 ER PT J AU Halim, T Burgett, M Donaldson, TK Savisaar, C Bowsher, J Clarke, IC AF Halim, Thomas Burgett, Michelle Donaldson, Thomas K. Savisaar, Christina Bowsher, John Clarke, Ian C. TI Profiling the third-body wear damage produced in CoCr surfaces by bone cement, CoCr, and Ti6Al4V debris: A 10-cycle metal-on-metal simulator test SO PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE LA English DT Article DE Hip simulator; metal-on-metal; CoCr; third-body wear ID TOTAL HIP-ARTHROPLASTY; CROSS-LINKED POLYETHYLENE; IN-VIVO; BEARING SURFACES; ACETABULAR CUPS; ABRASIVE WEAR; IMPINGEMENT; PARTICLES; EMBEDMENT; PATTERNS AB Particles of bone cement (polymethyl methacrylate), CoCr and Ti6Al4V were compared for their abrasion potential against CoCr substrates. This appears to be the first study utilizing CoCr and Ti6Al4V particulates to abrade CoCr bearings and the first study profiling the morphology of third-body abrasive wear scratches in a hip simulator. The 5 mg debris allotments (median size range 140-300 mu m) were added to cups mounted both inverted and anatomically with metal-on-metal (MOM) bearings in a 10-cycle, hip simulator test. Surface abrasion was characterized by roughness indices and scratch profiles. Compared to third-body abrasion with metal debris, polymethyl methacrylate debris had minimal effect on the CoCr surfaces. In all, 10 cycles of abrasion with metal debris demonstrated that roughness indices (Ra, PV) increased approximately 20-fold from the unworn condition. The scratch profiles ranged 20-108 mu m wide and 0.5-2.8 mu m deep. The scratch aspect ratio (W/PV) averaged 0.03, and this very low ratio indicated that the 140 mu m CoCr beads had plastically deformed to create wide but shallow scratches. There was no evidence of transfer of CoCr beads to CoCr bearings. The Ti64 particles produced similar scratch morphology with the same aspect ratio as the CoCr particulates. However, the titanium particulates also showed a unique ability to flatten and adhere to the CoCr, forming smears and islands of contaminating metal on the CoCr bearings. The morphology of scratches and metal transfer produced by these large metal particulates in the simulator appeared identical to those reported on retrieved metal-on-metal bearings. C1 [Halim, Thomas; Burgett, Michelle; Donaldson, Thomas K.; Clarke, Ian C.] Donaldson Arthrit Res Fdn, Colton, CA USA. [Savisaar, Christina] US FDA, Orthoped Joints Devices Branch, DSORD, ODE,CDRH, Silver Spring, MD USA. [Bowsher, John] US FDA, Anterior Spine Devices Branch, DOD, ODE,CDRH, Silver Spring, MD USA. [Clarke, Ian C.] Loma Linda Univ, LLUMC, Dept Orthoped, Loma Linda, CA 92354 USA. RP Clarke, IC (reprint author), Loma Linda Univ, LLUMC, Dept Orthoped, Rehabil Bldg,11406 Loma Linda Dr, Loma Linda, CA 92354 USA. EM hipgeek5@yahoo.com FU FDA [FDA1090372] FX This MOM simulator study was supported by the FDA contract "Development and Validation of Improved Premarket Testing Methods (simulator wear studies) for Metal-on-Metal (MOM) Hip Replacements" (FDA1090372). NR 52 TC 4 Z9 5 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0954-4119 EI 2041-3033 J9 P I MECH ENG H JI Proc. Inst. Mech. Eng. Part H-J. Eng. Med. PD JUL PY 2014 VL 228 IS 7 BP 703 EP 713 DI 10.1177/0954411914538782 PG 11 WC Engineering, Biomedical SC Engineering GA AN6TD UT WOS:000340729200007 PM 25062741 ER PT J AU Carlsen, EA Bang, LE Kober, L Strauss, DG Amaral, M Barbagelata, A Warren, S Wagner, GS AF Carlsen, Esben A. Bang, Lia E. Kober, Lars Strauss, David G. Amaral, Matias Barbagelata, Alejandro Warren, Stafford Wagner, Galen S. TI Availability of a baseline Electrocardiogram changes the application of the Sclarovsky-Birnbaum Myocardial Ischemia Grade SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Electrocardiogram; Sclarovsky-Birnbaum Ischemia Grade; STEMI; Myocardial ischemia ID ACUTE CORONARY-OCCLUSION; ST-SEGMENT ELEVATION; LUMINAL BALLOON ANGIOPLASTY; ADMISSION ELECTROCARDIOGRAM; QRS COMPLEX; INFARCT SIZE; PROGNOSTIC-SIGNIFICANCE; TRANSIENT ALTERATIONS; TERMINAL PORTION; COLLATERAL FLOW AB Background and aims: The electrocardiogram (ECG) based Sclarovsky-Birnbaum Ischemia Grade may be used to determine the prognosis of patients with ST-elevation myocardial infarction (STEMI). However, application of the method is based on assumption of the baseline QRS morphology. Thus, the aims of this study were to determine if the baseline QRS morphology was correctly assumed based on an ECG recorded during induced ischemia, and if reference to the baseline ECG altered the designated Ischemia Grade. Methods: Sixty-three patients with chronic ischemic heart disease that underwent elective percutaneous transluminal coronary angioplasty were included. Baseline ECG and ECG during the procedure were recorded. In the latter, Ischemia Grade was classified according to assumed baseline QRS morphology. Then the baseline ECG was used as reference and Ischemia Grade was determined based on change from the baseline ECG. Results: In 66.6% (42/63) of patients the criteria for STEMI were fulfilled; the incidence was similar between left anterior descending (LAD) and right coronary artery (RCA) occlusion. In LAD patients who fulfilled STEMI criteria, assumption of baseline QRS morphology in involved leads was accurate in only 35% (7/20) and this altered the Ischemia Grade in 10% (2/20) of patients. In RCA patients who fulfilled STEMI criteria, assumption of baseline QRS morphology in involved leads was accurate in 77.3% (17/22) and this altered the Ischemia Grade in 9.1% (2/22) of patients. Conclusion: Application of the Sclarovsky-Birnbaum Ischemia Grade with reference to a baseline ECG altered Ischemia Grade in approximately 10% of patients. All patients that were reclassified were assigned a higher Ischemia Grade. Future research is needed to determine the impact of availability of the baseline ECG on the clinical diagnostic and prognostic performances of the Sclarovsky-Birnbaum Ischemia Grade. (c) 2014 Elsevier Inc. All rights reserved. C1 [Carlsen, Esben A.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Bang, Lia E.; Kober, Lars] Copenhagen Univ Hosp, Ctr Heart, Dept Cardiol, Copenhagen, Denmark. [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Amaral, Matias; Barbagelata, Alejandro] Univ Texas Med Branch, Div Cardiol, Galveston, TX 77555 USA. [Warren, Stafford] Chesapeake Cardiac Care, Annapolis, MD USA. [Wagner, Galen S.] Duke Univ, Med Ctr, Durham, NC USA. RP Carlsen, EA (reprint author), Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. EM e_a_carlsen@hotmail.com NR 23 TC 3 Z9 3 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD JUL-AUG PY 2014 VL 47 IS 4 BP 571 EP 576 DI 10.1016/j.jelectrocard.2014.02.010 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AN3TK UT WOS:000340511400025 PM 24881971 ER PT J AU Jain, L Jadhav, P Gobburu, J AF Jain, Lokesh Jadhav, Pravin Gobburu, Jogarao TI Implications of choosing a correlation structure on model selection and parameter estimation SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE biological correlation; statistical correlation; population PK ID LABELING DECISIONS; DRUG APPLICATIONS; IMPACT; PHARMACOMETRICS; VARIABILITY; APPROVAL; ERROR AB The purpose of this research was to evaluate implications of choosing a statistical or biological correlation structure on model selection and parameter estimation. A series of simulations and estimations were performed with and without biological (weight as a common covariate) or statistical (off diagonal element in omega matrix) correlation between clearance (CL) and volume of distribution (V-d). One-compartment model with IV bolus administration was used with 30% interindividual variability (%CV) on CL and Yd. The results were compared for model selection, parameter equivalence, bias, and imprecision. We found that estimation of fixed-effect parameters (CL, V-d) was robust and estimates of random-effect parameters were not influenced by inclusion or exclusion of statistical correlation irrespective of true correlation structure. However, CVCL and CVV were inflated (by 18-35%) when true biological correlation was ignored or accounted for by statistical correlation. It is important to note that in spite of the inflated estimates; these values represent the true variability in the simulated dataset, i.e., reflecting the random variance plus the variance associated with weight. Therefore, if statistical correlation was used in absence of true covariate information, the range of individual parameters in future simulations would be similar compared to a model that uses true biological correlation. A true correlation structure is unknown for real life examples; a statistical correlation is a suitable alternative. C1 [Jain, Lokesh] US FDA, Div Clin Pharmacol, Silver Spring, MD USA. [Jadhav, Pravin] Merck Sharp & Dohme Corp, Modeling & Simulat, Upper Gwynedd, PA USA. [Gobburu, Jogarao] Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, Baltimore, MD 21201 USA. RP Gobburu, J (reprint author), Univ Maryland, Sch Pharm, Ctr Translat Med, 20 North Pine St, Baltimore, MD 21201 USA. EM jgobburu@rx.umaryland.edu NR 19 TC 0 Z9 0 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD JUL PY 2014 VL 52 IS 7 BP 598 EP 611 DI 10.5414/CP202058 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AM9XE UT WOS:000340233500006 PM 24725444 ER PT J AU Aloraefy, M Pfefer, TJ Ramella-Roman, JC Sapsford, KE AF Aloraefy, Mamdouh Pfefer, T. Joshua Ramella-Roman, Jessica C. Sapsford, Kim E. TI In Vitro Evaluation of Fluorescence Glucose Biosensor Response SO SENSORS LA English DT Article DE affinity biosensor; competitive binding; concanavalin A; continuous glucose monitoring; fluorescence sensor; FRET-based; glucose sensor; minimally-invasive; optical ID MIDINFRARED LASER SPECTROSCOPY; COMPETITIVE-BINDING ASSAY; AFFINITY SENSOR; DIABETES MANAGEMENT; LINEAR-REGRESSION; ENERGY-TRANSFER; BLOOD-GLUCOSE; CONCANAVALIN; MICROSPHERES; PERFORMANCE AB Rapid, accurate, and minimally-invasive glucose biosensors based on F rster Resonance Energy Transfer (FRET) for glucose measurement have the potential to enhance diabetes control. However, a standard set of in vitro approaches for evaluating optical glucose biosensor response under controlled conditions would facilitate technological innovation and clinical translation. Towards this end, we have identified key characteristics and response test methods, fabricated FRET-based glucose biosensors, and characterized biosensor performance using these test methods. The biosensors were based on competitive binding between dextran and glucose to concanavalin A and incorporated long-wavelength fluorescence dye pairs. Testing characteristics included spectral response, linearity, sensitivity, limit of detection, kinetic response, reversibility, stability, precision, and accuracy. The biosensor demonstrated a fluorescence change of 45% in the presence of 400 mg/dL glucose, a mean absolute relative difference of less than 11%, a limit of detection of 25 mg/dL, a response time of 15 min, and a decay in fluorescence intensity of 72% over 30 days. The battery of tests presented here for objective, quantitative in vitro evaluation of FRET glucose biosensors performance have the potential to form the basis of future consensus standards. By implementing these test methods for a long-visible-wavelength biosensor, we were able to demonstrate strengths and weaknesses with a new level of thoroughness and rigor. C1 [Aloraefy, Mamdouh; Pfefer, T. Joshua; Sapsford, Kim E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Aloraefy, Mamdouh] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. [Ramella-Roman, Jessica C.] Florida Int Univ, Dept Biomed Engn, Miami, FL 33174 USA. [Ramella-Roman, Jessica C.] Florida Int Univ, Herbert Wertheim Coll Med, Miami, FL 33174 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM Mamdouh.Aloraefy@fda.hhs.gov; Joshua.Pfefer@fda.hhs.gov; jramella@fiu.edu; Kim.Sapsford@fda.hhs.gov NR 61 TC 5 Z9 5 U1 3 U2 31 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1424-8220 J9 SENSORS-BASEL JI Sensors PD JUL PY 2014 VL 14 IS 7 BP 12127 EP 12148 DI 10.3390/s140712127 PG 22 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA AM7HF UT WOS:000340035700046 PM 25006996 ER PT J AU Nyan, DC Ulitzky, LE Cehan, N Williamson, P Winkelman, V Rios, M Taylor, DR AF Nyan, Dougbeh-Chris Ulitzky, Laura E. Cehan, Nicoleta Williamson, Phillip Winkelman, Valerie Rios, Maria Taylor, Deborah R. TI Rapid Detection of Hepatitis B Virus in Blood Plasma by a Specific and Sensitive Loop-Mediated Isothermal Amplification Assay SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE hepatitis B virus; loop-mediated isothermal amplification; nucleotide; rapid detection; international units per reaction ID STRAND DISPLACEMENT AMPLIFICATION; UNITED-STATES; HBV INFECTION; C VIRUS; DNA; PREVALENCE; TRAVELERS; GENOTYPE; REFUGEES; SEQUENCE AB Background. Hepatitis B virus (HBV) is an important blood-borne pathogen that causes hepatic inflammation and can lead to liver cirrhosis and hepatocellular carcinoma. Conventional methods of HBV detection are time consuming and require highly trained personnel and elaborate equipment. This report describes the development of a rapid, simple, specific, and sensitive loop-mediated isothermal amplification assay (LAMP) for detection of HBV genotypes A, B, C, D, E, and F in blood samples. Methods. HBV standard plasma panels and clinical donor plasma specimens were used for the development and validation of the LAMP assay. Amplification was performed at 60 C for 60 minutes using extracted DNA or heat-treated plasma specimens without DNA extraction. The assay was evaluated for its ability to detect various HBV genotypes and for its sensitivity, specificity, and time-point of detection. Results. The LAMP assay detected HBV genotypes A-F and demonstrated a sensitivity of 10-100 IU per reaction of HBV DNA. The assay also detected 69 of 75 (92%) HBV-positive donor plasma specimens tested and demonstrated a specificity of 100%. Conclusions. These results demonstrate that our HBV-LAMP assay is rapid, sensitive and specific, and capable of detecting the major HBV genotypes. This assay could be used in clinical point-of-care settings, mainly in endemic and resource-limited environments for HBV diagnostics, donor screening, epidemiological studies, and therapeutic monitoring of patients undergoing antiviral treatment. C1 [Nyan, Dougbeh-Chris; Ulitzky, Laura E.; Cehan, Nicoleta; Rios, Maria; Taylor, Deborah R.] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res,Off Blood Res & Review, Bethesda, MD 20892 USA. [Williamson, Phillip; Winkelman, Valerie] Creat Testing Solut, Tempe, AZ USA. RP Taylor, DR (reprint author), US FDA, DETTD, CBER, 8800 Rockville Pike,NIH Bldg 29,Rm 131, Bethesda, MD 20892 USA. EM deborah.taylor@fda.hhs.gov FU Department of Energy; FDA FX This work was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the Department of Energy and the FDA. NR 43 TC 11 Z9 15 U1 2 U2 20 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2014 VL 59 IS 1 BP 16 EP 23 DI 10.1093/cid/ciu210 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AM2FL UT WOS:000339665000005 PM 24704724 ER PT J AU Morine, MJ Monteiro, JP Wise, C Teitel, C Pence, L Williams, A Ning, BT McCabe-Sellers, B Champagne, C Turner, J Shelby, B Bogle, M Beger, RD Priami, C Kaput, J AF Morine, Melissa J. Monteiro, Jacqueline Pontes Wise, Carolyn Teitel, Candee Pence, Lisa Williams, Anna Ning, Baitang McCabe-Sellers, Beverly Champagne, Catherine Turner, Jerome Shelby, Beatrice Bogle, Margaret Beger, Richard D. Priami, Corrado Kaput, Jim TI Genetic associations with micronutrient levels identified in immune and gastrointestinal networks SO GENES AND NUTRITION LA English DT Article DE Systems nutrition; Community-based participatory research; Genetic analysis; Network analysis ID SYSTEMS BIOLOGY; ENVIRONMENTAL-FACTORS; NUTRIGENOMICS; GENOMICS; DISEASE; INDIVIDUALITY; MALNUTRITION; ARCHITECTURE; METAANALYSIS; NUTRITION AB The discovery of vitamins and clarification of their role in preventing frank essential nutrient deficiencies occurred in the early 1900s. Much vitamin research has understandably focused on public health and the effects of single nutrients to alleviate acute conditions. The physiological processes for maintaining health, however, are complex systems that depend upon interactions between multiple nutrients, environmental factors, and genetic makeup. To analyze the relationship between these factors and nutritional health, data were obtained from an observational, community-based participatory research program of children and teens (age 6-14) enrolled in a summer day camp in the Delta region of Arkansas. Assessments of erythrocyte S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), plasma homocysteine (Hcy) and 6 organic micronutrients (retinol, 25-hydroxy vitamin D3, pyridoxal, thiamin, riboflavin, and vitamin E), and 1,129 plasma proteins were performed at 3 time points in each of 2 years. Genetic makeup was analyzed with 1 M SNP genotyping arrays, and nutrient status was assessed with 24-h dietary intake questionnaires. A pattern of metabolites (met_PC1) that included the ratio of erythrocyte SAM/SAH, Hcy, and 5 vitamins were identified by principal component analysis. Met_C1 levels were significantly associated with (1) single-nucleotide polymorphisms, (2) levels of plasma proteins, and (3) multilocus genotypes coding for gastrointestinal and immune functions, as identified in a global network of metabolic/protein-protein interactions. Subsequent mining of data from curated pathway, network, and genome-wide association studies identified genetic and functional relationships that may be explained by gene-nutrient interactions. The systems nutrition strategy described here has thus associated a multivariate metabolite pattern in blood with genes involved in immune and gastrointestinal functions. C1 [Morine, Melissa J.; Priami, Corrado] Microsoft Res Univ Trento, Ctr Computat & Syst Biol COSBI, Rovereto, Italy. [Morine, Melissa J.; Priami, Corrado] Univ Trento, Dept Math, Trento, Italy. [Monteiro, Jacqueline Pontes] Univ Sao Paulo, Fac Med Nutr & Metab, Dept Pediat, Ribeirao Preto, SP, Brazil. [Wise, Carolyn; Teitel, Candee; Williams, Anna; Ning, Baitang] Natl Ctr Toxicol Res, Food & Drug Adm NCTR FDA, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Pence, Lisa; Beger, Richard D.] Natl Ctr Toxicol Res, Food & Drug Adm, Div Syst Biol, Jefferson, AR 72079 USA. [McCabe-Sellers, Beverly; Bogle, Margaret] ARS, USDA, Delta Obes Prevent Res Unit, Little Rock, AR USA. [Champagne, Catherine] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Turner, Jerome; Shelby, Beatrice] Boys Girls & Adults Community Dev Ctr, Marvell, AR USA. [Turner, Jerome; Shelby, Beatrice] Phillips Cty Community Partners, Marvell, AR USA. [Kaput, Jim] Nestle Inst Hlth Sci, Syst Nutr & Hlth Unit, Lausanne, Switzerland. RP Kaput, J (reprint author), Nestle Inst Hlth Sci, Syst Nutr & Hlth Unit, Lausanne, Switzerland. EM jacque160165@gmail.com; James.Kaput@rd.nestle.com RI Monteiro, Jacqueline/F-6987-2012 FU Division of Personalized Nutrition and Medicine at the US FDA National Center for Toxicological Research (Jefferson, AR); USDA Agricultural Research Service Delta Obesity Prevention Research Unit (Little Rock, AR); Nestle Institute of Health Sciences (Lausanne, Switzerland); Division of Personalized Nutrition and Medicine at the US FDA National Center for Toxicological Research (Jefferson AR) FX This research was funded by the Division of Personalized Nutrition and Medicine at the US FDA National Center for Toxicological Research (Jefferson, AR), the USDA Agricultural Research Service Delta Obesity Prevention Research Unit (Little Rock, AR), and the Nestle Institute of Health Sciences (Lausanne, Switzerland). The research team gratefully acknowledges the contributions of the Phillips County community members in the Marvell (AR) School District for their participation in this research. This research was funded by the Division of Personalized Nutrition and Medicine at the US FDA National Center for Toxicological Research (Jefferson AR), the USDA Agricultural Research Service Delta Obesity Prevention Research Unit (Little Rock, AR), and the Nestle Institute of Health Sciences (Lausanne, Switzerland). We thank Donna Mendrick, Li-Rong Yu, and Ritchie Feurs for critically reading this manuscript. NR 68 TC 5 Z9 5 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1555-8932 EI 1865-3499 J9 GENES NUTR JI Genes Nutr. PD JUL PY 2014 VL 9 IS 4 AR 408 DI 10.1007/s12263-014-0408-4 PG 19 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA AM4FN UT WOS:000339808800005 PM 24879315 ER PT J AU Faison, WJ Rostovtsev, A Castro-Nallar, E Crandall, KA Chumakov, K Simonyan, V Mazumder, R AF Faison, William J. Rostovtsev, Alexandre Castro-Nallar, Eduardo Crandall, Keith A. Chumakov, Konstantin Simonyan, Vahan Mazumder, Raja TI Whole genome single-nucleotide variation profile-based phylogenetic tree building methods for analysis of viral, bacterial and human genomes SO GENOMICS LA English DT Article DE Phylogenetic; Next-generation sequencing; SNP; SNV; Cancer genomics; Vaccine quality control ID WEB-SERVER; POLIO; SNP; ALGORITHM; GENETICS AB Next-generation sequencing data can be mapped to a reference genome to identify single-nucleotide polymorphisms/variations (SNPs/SNVs; called SNPs hereafter). In theory, SNPs can be compared across several samples and the differences can be used to create phylogenetic trees depicting relatedness among the samples. However, in practice this is difficult because currently there is no stand-alone tool that takes SNP data directly as input and produces phylogenetic trees. In response to this need, PhyloSNP application was created with two analysis methods 1) a quantitative method that creates the presence/absence matrix which can be directly used to generate phylogenetic trees or creates a tree from a shrunk genome alignment (includes additional bases surrounding the SNP position) and 2) a qualitative method that clusters samples based on the frequency of different bases found at a particular position. The algorithms were used to generate trees from Poliovirus, Burkholderia and human cancer genomics NGS datasets. (C) 2014 Elsevier Inc. All rights reserved. C1 [Faison, William J.; Mazumder, Raja] George Washington Univ, Med Ctr, Dept Biochem & Mol Med, Washington, DC 20037 USA. [Rostovtsev, Alexandre; Chumakov, Konstantin; Simonyan, Vahan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Castro-Nallar, Eduardo; Crandall, Keith A.] George Washington Univ, Computat Biol Inst, Ashburn, VA 20147 USA. [Mazumder, Raja] George Washington Univ, McCormick Genom & Prote Ctr, Washington, DC 20037 USA. RP Mazumder, R (reprint author), George Washington Univ, Med Ctr, Dept Biochem & Mol Med, Washington, DC 20037 USA. EM Jamie_Faison@gwmail.gwu.edu; Alexandre.Rostovtsev@fda.hhs.gov; Ecastron@gwmail.gwu.edu; kcrandall@gwu.edu; Konstantin.Chumakov@fda.hhs.gov; Vahan.Simonyan@fda.hhs.gov; Mazumder@gwu.edu OI Castro-Nallar, Eduardo/0000-0003-4384-8661; Crandall, Keith/0000-0002-0836-3389 FU High-performance Integrated Virtual Environment (HIVE); collaborative research grant [CTSI-CN/GW/VT (IXXS90459N)]; Research Participation Program at the CBER FX PhyloSNP development is supported by High-performance Integrated Virtual Environment (HIVE). The HIVE project led by Dr. Mazumder and Dr. Simonyan supports Big Data analysis which includes next-generation sequence analysis and storage (http://hive.biochemistry. gwu.edu/). We would like to thank Hayley Dingerdissen and Pan Yang for providing useful comments. This project is supported in part by the Research Participation Program at the CBER administered by the ORISE through an interagency agreement between the USDOE, the USFDA and CTSI-CN/GW/VT (IXXS90459N) collaborative research grant to RM. NR 22 TC 4 Z9 4 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD JUL PY 2014 VL 104 IS 1 BP 1 EP 7 DI 10.1016/j.ygeno.2014.06.001 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AM7CE UT WOS:000340021500001 PM 24930720 ER PT J AU Ridge, CD MacMahon, S Mazzola, EP AF Ridge, C. D. MacMahon, S. Mazzola, E. P. TI Using very high-resolution carbon-detected NMR experiments for more complete assignment of fatty acid esters SO PLANTA MEDICA LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-of-Pharmacognosy (ASP) CY AUG 02-06, 2014 CL Oxford, MS SP Amer Soc Pharmacognosy ID FLOCK SEQUENCE C1 [Ridge, C. D.; MacMahon, S.; Mazzola, E. P.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 EI 1439-0221 J9 PLANTA MED JI Planta Med. PD JUL PY 2014 VL 80 IS 10 MA CL23 BP 762 EP 762 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AM3VP UT WOS:000339781200067 ER PT J AU Avonto, C Wang, YH Avula, B Wang, M Rua, D Khan, IA AF Avonto, C. Wang, Y. H. Avula, B. Wang, M. Rua, D. Khan, I. A. TI Investigation of the instability of alpha and beta-arbutin SO PLANTA MEDICA LA English DT Meeting Abstract CT 55th Annual Meeting of the American-Society-of-Pharmacognosy (ASP) CY AUG 02-06, 2014 CL Oxford, MS SP Amer Soc Pharmacognosy C1 [Avonto, C.; Wang, Y. H.; Avula, B.; Wang, M.; Khan, I. A.] Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Natl Ctr Nat Prod Res, University, MS 38677 USA. [Khan, I. A.] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA. [Rua, D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Khan, I. A.] King Saud Univ, Coll Pharm, Dept Pharmacognosy, Riyadh, Saudi Arabia. NR 0 TC 0 Z9 0 U1 1 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 EI 1439-0221 J9 PLANTA MED JI Planta Med. PD JUL PY 2014 VL 80 IS 10 MA PPL23 BP 830 EP 830 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AM3VP UT WOS:000339781200371 ER PT J AU Rebuli, ME Cao, JY Sluzas, E Delclos, KB Camacho, L Lewis, SM Vanlandingham, MM Patisaul, HB AF Rebuli, Meghan E. Cao, Jinyan Sluzas, Emily Delclos, K. Barry Camacho, Luisa Lewis, Sherry M. Vanlandingham, Michelle M. Patisaul, Heather B. TI Investigation of the Effects of Subchronic Low Dose Oral Exposure to Bisphenol A (BPA) and Ethinyl Estradiol (EE) on Estrogen Receptor Expression in the Juvenile and Adult Female Rat Hypothalamus SO TOXICOLOGICAL SCIENCES LA English DT Article DE brain; endocrine disruptor; endocrine disruption; hypothalamus; development; subchronic exposure; sexually dimorphic; ethinyl estradiol; bisphenol A ID SEXUALLY DIMORPHIC EXPRESSION; SPRAGUE-DAWLEY RATS; ALPHA ER-ALPHA; GENE-EXPRESSION; MESSENGER-RNA; PREOPTIC AREA; POSTNATAL-DEVELOPMENT; NEONATAL EXPOSURE; SEX-DIFFERENCES; NERVOUS-SYSTEM AB Concerns have been raised regarding the long-term impacts of early life exposure to the ubiquitous environmental contaminant bisphenol A (BPA) on brain organization. Because BPA has been reported to affect estrogen signaling, and steroid hormones play a critical role in brain sexual differentiation, there is also concern that BPA exposure could alter neural sex differences. Here, we examine the impact of subchronic exposure from gestation to adulthood to oral doses of BPA below the current no-observed-adverse-effect level (NOAEL) of 5 mg/kg body weight (bw)/day on estrogen receptor (ESR) expression in sexually dimorphic brain regions of prepubertal and adult female rats. The dams were gavaged daily with vehicle (0.3% carboxymethylcellulose), 2.5, 25, 260, or 2700 mu g BPA/kg bw/day, or 0.5 or 5.0 mu g ethinyl estradiol (EE)/kg bw/day from gestational day 6 until labor began. Offspring were then gavaged directly from the day after birth until the day before scheduled sacrifice on postnatal days 21 or 90. Using in situ hybridization, one or more BPA doses produced significant decreases in Esr1 expression in the juvenile female rat anteroventral periventricular nucleus (AVPV) of the hypothalamus and significant decreases in Esr2 expression in the adult female rat AVPV and medial preoptic area (MPOA), relative to vehicle controls. BPA did not simply reproduce EE effects, indicating that BPA is not acting solely as an estrogen mimic. The possible consequences of long-term changes in hypothalamic ESR expression resulting from subchronic low dose BPA exposure on neuroendocrine effects are discussed and being addressed in ongoing, related work. C1 [Rebuli, Meghan E.; Cao, Jinyan; Sluzas, Emily; Patisaul, Heather B.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. [Delclos, K. Barry; Camacho, Luisa; Lewis, Sherry M.; Vanlandingham, Michelle M.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Rebuli, Meghan E.; Cao, Jinyan; Patisaul, Heather B.] N Carolina State Univ, Keck Ctr Behav Biol, Raleigh, NC 27695 USA. RP Patisaul, HB (reprint author), N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. EM Heather_Patisaul@ncsu.edu FU National Toxicology Program (NTP) [C10034]; Food and Drug Administration (FDA) [FDA IAG: 224-12-0003, NIEHS IAG: AES12013]; National Institute of Environmental Health Sciences (NIEHS)/National Institutes of Health [FDA IAG: 224-12-0003, NIEHS IAG: AES12013] FX The brain region receptor measurements were supportedby the National Institutes of Health [R01-16001-04S1 to H. B. P.]. The animal treatment and tissue collection were conducted at NCTR under the auspices of the National Toxicology Program (NTP Study # C10034) and funded by an Interagency agreement (IAG) between the Food and Drug Administration (FDA) and the National Institute of Environmental Health Sciences (NIEHS)/National Institutes of Health [FDA IAG: 224-12-0003; NIEHS IAG: AES12013]. NR 90 TC 17 Z9 20 U1 2 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2014 VL 140 IS 1 BP 190 EP 203 DI 10.1093/toxsci/kfu074 PG 14 WC Toxicology SC Toxicology GA AM3AB UT WOS:000339722100017 PM 24752507 ER PT J AU Lee, LM Marks, P AF Lee, Lisa M. Marks, Peter TI When a Blood Donor Has Sickle Cell Trait: Incidental Findings and Public Health SO HASTINGS CENTER REPORT LA English DT Article C1 [Marks, Peter] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 25 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0093-0334 EI 1552-146X J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JUL-AUG PY 2014 VL 44 IS 4 BP 17 EP 21 DI 10.1002/hast.327 PG 6 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA AM0HD UT WOS:000339524100012 PM 25043363 ER PT J AU Miranda-Bermudez, E Harp, BP Barrows, JN AF Miranda-Bermudez, Enio Harp, Bhakti Petigara Barrows, Julie N. TI Qualitative Identification of Permitted and Non-permitted Color Additives in Cosmetics SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ORGANIC COLORANTS; ARRAY DETECTION; DYES; PRODUCTS AB Color additives are dyes, pigments, or other substances that can impart color when added or applied to foods, drugs, cosmetics, medical devices, or the human body. These substances must be pre-approved by the U.S. Food and Drug Administration (FDA) and listed in the Code of Federal Regulations before they may be used in FDA-regulated products. Both domestic and imported cosmetic products sold in interstate commerce fall under FDA jurisdiction, and FDA's district laboratories use a combination of analytical methods for identifying or confirming the presence of potentially violative color additives. We have developed a qualitative method for identifying 29 water- and methanol-soluble color additives in various types of cosmetic products. The color additives are extracted with combinations of methylene chloride, methanol, acetic acid, and water and are identified by LC with photodiode array detection. Estimated LOD values ranged from 0.1 to 1.5 mg/L. A survey of lip products, nail polishes, eye products, blushes, body glitter, face paints, bath products, creams, and toothpastes identified permitted and non-permitted color additives. Our new LC method is intended to supplement the visible spectrophotometry and TLC methods currently used by FDA's district laboratories and will help optimize the use of time, labor, and solvents. C1 [Miranda-Bermudez, Enio; Harp, Bhakti Petigara; Barrows, Julie N.] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. RP Miranda-Bermudez, E (reprint author), US FDA, Off Cosmet & Colors, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM enio.miranda-bermudez@fda.hhs.gov NR 12 TC 1 Z9 1 U1 3 U2 22 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2014 VL 97 IS 4 BP 1039 EP 1047 DI 10.5740/jaoacint.14-025 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA AM0LT UT WOS:000339537800012 PM 25145135 ER PT J AU Hait, JM Tallent, SM Bennett, RW AF Hait, Jennifer M. Tallent, Sandra M. Bennett, Reginald W. TI Screening, Detection, and Serotyping Methods for Toxin Genes and Enterotoxins in Staphylococcus Strains SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID OUTBREAK; IDENTIFICATION; INTERMEDIUS AB Staphylococcus aureus continues to play a significant role in foodborne outbreak investigations, with numerous individuals sickened each year after ingesting assorted foods contaminated with staphylococcal enterotoxins. The purpose of this study was to evaluate the use of several methods for the screening, detection, and enterotoxin serotyping of staphylococcal bacterial strains for classical staphylococcal enterotoxins (SEs; SEA, SEB, SEC, SED, and SEE) and the newly described SE and SE-like enterotoxin genes (seg, seh, sei, sej, sek, sel, sem, sen, seo, sep, seq, ser, ses, set, and seu). Inclusivity and exclusivity panels of staphylococcal strains were tested using a multiplex PCR method in addition to three polyvalent commercially prepared ELISA systems for the detection of SEA-SEE and one monovalent assay for the identification of classical SE serotypes. The results indicate an overall agreement between serological detection methods with a few exceptions, and molecular characterization identified an abundance of SE and SE-like enterotoxin genes including several potentially enterotoxigenic isolates that would have otherwise been missed by ELISA-based methods. These findings demonstrate the significance of PCR for future screening purposes and the use of ELISA systems for the detection and enterotoxin serotyping of staphylococcal bacterial strains. C1 [Hait, Jennifer M.; Tallent, Sandra M.; Bennett, Reginald W.] US FDA, College Pk, MD 20740 USA. RP Hait, JM (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jennifer.hait@fda.hhs.gov FU NARSA Program under National Institute of Allergy and Infectious Diseases (NIAID) [NRS1, NRS100, NRS108, NRS109, NRS110, NRS111, NRS112, NRS114, NRS119, NRS120, NRS121, NRS127, NRS194, NRS271, NRS6, NRS7, NRS8, NRS9, NRS53, NRS60, NRS69, NRS101, NRS106, NRS116, NRS122, NRS130, NRS138]; National Institutes of Health (NIH) [HHSN272200700055C] FX The following isolates were obtained through the NARSA Program: < NRS1, NRS100, NRS108, NRS109, NRS110, NRS111, NRS112, NRS114, NRS119, NRS120, NRS121, NRS127, NRS194, NRS271, NRS6, NRS7, NRS8, NRS9, NRS53, NRS60, NRS69, NRS101, NRS106, NRS116, NRS122, NRS130, and NRS138 > supported under National Institute of Allergy and Infectious Diseases (NIAID) and National Institutes of Health (NIH) Contract No. HHSN272200700055C. NR 20 TC 2 Z9 2 U1 1 U2 20 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2014 VL 97 IS 4 BP 1078 EP 1083 DI 10.5740/jaoacint.13-211 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA AM0LT UT WOS:000339537800018 PM 25145141 ER PT J AU Chen, Y Reddy, RM McLaughlin, MA Al-Taher, F Yettella, RR Uhlig, S Blaul, C AF Chen, Yang Reddy, Ravinder M. McLaughlin, Michael A. Al-Taher, Fadwa Yettella, Ramesh R. Uhlig, Steffen Blaeul, Christian TI Method Validation and Proficiency Testing for Determination of Total Arsenic in Apple Juice by Inductively Coupled Plasma/Mass Spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ANALYTICAL-CHEMISTRY; MASS SPECTROMETRY; QUALITY-CONTROL; EXPOSURE; SPECIATION; WATER AB A proficiency test (PT) program for determination of total As in apple juice samples was conducted by the Food Emergency Response Network (FERN) laboratories. An analytical method using inductively coupled plasma (ICP)-MS was validated for this project. The LOD and LOQ were determined to be 0.315 and 2.32 ng/g, respectively. A total of eight apple juice samples were sent to 38 FERN laboratories, and results were statistically evaluated according to ISO 13528:2005. The total As concentrations in the PT samples reported by the participating laboratories were very close to those obtained in the homogeneity and stability tests. The reproducibility, repeatability, interlaboratory, and intralaboratory variability results led to 69% of participating laboratories being rated as satisfactory using the widely accepted vertical bar z vertical bar score <= 2 criterion. The percentage of laboratories with acceptable z scores (vertical bar z vertical bar scores <= 2) increased from 61 to 89% with the increase in As concentration in PT samples from 5.05 to 30.72 ng/g. This study demonstrated that the ICP/MS method was adequate for total As determination in fruit juice, and most of the participating laboratories were proficient in their analytical performance. C1 [Chen, Yang; Reddy, Ravinder M.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. [McLaughlin, Michael A.] US FDA, Off Regulatory Affairs, College Pk, MD 20740 USA. [Al-Taher, Fadwa; Yettella, Ramesh R.] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Uhlig, Steffen; Blaeul, Christian] QuoData GmbH, D-01187 Dresden, Germany. RP Chen, Y (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM yang.chen@fda.hhs.gov FU Research Program appointment at the Center for Food Safety and Applied Nutrition; U.S. Department of Energy; FDA FX This project was supported in part by a Research Program appointment at the Center for Food Safety and Applied Nutrition administrated by the Oak Ridge Institute for Science and Education via an interagency agreement between the U.S. Department of Energy and the FDA. NR 31 TC 1 Z9 1 U1 3 U2 19 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2014 VL 97 IS 4 BP 1143 EP 1150 DI 10.5740/jaoacint.13-207 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA AM0LT UT WOS:000339537800027 PM 25145150 ER PT J AU Gutierrez, B Badano, A Samuelson, F AF Gutierrez, Benjamin Badano, Aldo Samuelson, Frank TI Analytic variance estimates of Swank and Fano factors SO MEDICAL PHYSICS LA English DT Article DE Swank Factor; Fano factor; variance; Monte Carlo simulation AB Purpose: Variance estimates for detector energy resolution metrics can be used as stopping criteria in Monte Carlo simulations for the purpose of ensuring a small uncertainty of those metrics and for the design of variance reduction techniques. Methods: The authors derive an estimate for the variance of two energy resolution metrics, the Swank factor and the Fano factor, in terms of statistical moments that can be accumulated without significant computational overhead. The authors examine the accuracy of these two estimators and demonstrate how the estimates of the coefficient of variation of the Swank and Fano factors behave with data from a Monte Carlo simulation of an indirect x-ray imaging detector. Results: The authors' analyses suggest that the accuracy of their variance estimators is appropriate for estimating the actual variances of the Swank and Fano factors for a variety of distributions of detector outputs. Conclusions: The variance estimators derived in this work provide a computationally convenient way to estimate the error or coefficient of variation of the Swank and Fano factors during Monte Carlo simulations of radiation imaging systems. (C) 2014 American Association of Physicists in Medicine. C1 [Gutierrez, Benjamin; Badano, Aldo; Samuelson, Frank] US FDA, Silver Spring, MD 20993 USA. RP Gutierrez, B (reprint author), US FDA, Silver Spring, MD 20993 USA. EM frank.samuelson@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU U.S. DOE; U.S. FDA FX The authors acknowledge funding by an appointment to the Research Participation Program at the CDRH administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. DOE and the U.S. FDA. The authors also acknowledge Diksha Sharma for providing the Monte Carlo outputs from her work. NR 7 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2014 VL 41 IS 7 AR 072102 DI 10.1118/1.4881328 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AL3EW UT WOS:000339009800031 PM 24989397 ER PT J AU Vaishnav, JY Jung, WC Popescu, LM Zeng, R Myers, KJ AF Vaishnav, J. Y. Jung, W. C. Popescu, L. M. Zeng, R. Myers, K. J. TI Objective assessment of image quality and dose reduction in CT iterative reconstruction SO MEDICAL PHYSICS LA English DT Article DE iterative reconstruction; dose reduction; computed tomography ID MODERN DIAGNOSTIC MDCT; NOISE POWER SPECTRUM; SIGNAL-TO-NOISE; CONE-BEAM CT; OBSERVER PERFORMANCE; COMPUTED-TOMOGRAPHY; HOTELLING-OBSERVER; MODEL-OBSERVER; LOCATION TASKS; DETECTABILITY AB Purpose: Iterative reconstruction (IR) algorithms have the potential to reduce radiation dose in CT diagnostic imaging. As these algorithms become available on the market, a standardizable method of quantifying the dose reduction that a particular IR method can achieve would be valuable. Such a method would assist manufacturers in making promotional claims about dose reduction, buyers in comparing different devices, physicists in independently validating the claims, and the United States Food and Drug Administration in regulating the labeling of CT devices. However, the nonlinear nature of commercially available IR algorithms poses challenges to objectively assessing image quality, a necessary step in establishing the amount of dose reduction that a given IR algorithm can achieve without compromising that image quality. This review paper seeks to consolidate information relevant to objectively assessing the quality of CT IR images, and thereby measuring the level of dose reduction that a given IR algorithm can achieve. Methods: The authors discuss task-based methods for assessing the quality of CT IR images and evaluating dose reduction. Results: The authors explain and review recent literature on signal detection and localization tasks in CT IR image quality assessment, the design of an appropriate phantom for these tasks, possible choices of observers (including human and model observers), and methods of evaluating observer performance. Conclusions: Standardizing the measurement of dose reduction is a problem of broad interest to the CT community and to public health. A necessary step in the process is the objective assessment of CT image quality, for which various task-based methods may be suitable. This paper attempts to consolidate recent literature that is relevant to the development and implementation of task-based methods for the assessment of CT IR image quality. (C) 2014 American Association of Physicists in Medicine. C1 [Vaishnav, J. Y.; Jung, W. C.] US FDA, Diagnost Xray Syst Branch, Off In Vitro Diagnost Devices & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Popescu, L. M.; Zeng, R.; Myers, K. J.] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Vaishnav, JY (reprint author), US FDA, Diagnost Xray Syst Branch, Off In Vitro Diagnost Devices & Radiol Hlth, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jay.vaishnav@fda.hhs.gov NR 55 TC 17 Z9 17 U1 0 U2 21 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2014 VL 41 IS 7 AR 071904 DI 10.1118/1.4881148 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AL3EW UT WOS:000339009800016 PM 24989382 ER PT J AU Meijs, LPB Galeotti, L Pueyo, EP Romero, D Jennings, RB Ringborn, M Warren, SG Wagner, GS Strauss, DG AF Meijs, Loek P. B. Galeotti, Loriano Pueyo, Esther P. Romero, Daniel Jennings, Robert B. Ringborn, Michael Warren, Stafford G. Wagner, Galen S. Strauss, David G. TI An electrocardiographic sign of ischemic preconditioning SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE acute myocardial infarction; electrocardiology; electrophysiology; quantitative modeling ID ACUTE MYOCARDIAL-ISCHEMIA; SENSITIVE POTASSIUM CHANNELS; CORONARY-ARTERY OCCLUSION; TIME COURSE; ST-SEGMENT; PIG-HEART; ANGIOPLASTY; INFARCTION; INJURY; REPOLARIZATION AB Ischemic preconditioning is a form of intrinsic cardioprotection where an episode of sublethal ischemia protects against subsequent episodes of ischemia. Identifying a clinical biomarker of preconditioning could have important clinical implications, and prior work has focused on the electrocardiographic ST segment. However, the electrophysiology biomarker of preconditioning is increased action potential duration (APD) shortening with subsequent ischemic episodes, and APD shortening should primarily alter the T wave, not the ST segment. We translated findings from simulations to canine to patient models of preconditioning to test the hypothesis that the combination of increased [delta (Delta)] T wave amplitude with decreased ST segment elevation characterizes preconditioning. In simulations, decreased APD caused increased T wave amplitude with minimal ST segment elevation. In contrast, decreased action potential amplitude increased ST segment elevation significantly. In a canine model of preconditioning (9 mongrel dogs undergoing 4 ischemia-reperfusion episodes), ST segment amplitude increased more than T wave amplitude during the first ischemic episode [Delta T/Delta ST slope = 0.81, 95% confidence interval (CI) 0.46 -1.15]; however, during subsequent ischemic episodes the T wave increased significantly more than the ST segment (Delta T/Delta ST slope = 2.43, CI 2.07-2.80) (P = 0.001 for interaction of occlusions 2 vs. 1). A similar result was observed in patients (9 patients undergoing 2 consecutive prolonged occlusions during elective percutaneous coronary intervention), with an increase in slope of Delta T/Delta ST of 0.13 (CI = 0.15 to 0.42) in the first occlusion to 1.02 (CI 0.31-1.73) in the second occlusion (P = 0.02). This integrated analysis of the T wave and ST segment goes beyond the standard approach to only analyze ST elevation, and detects cellular electrophysiology changes of preconditioning. C1 [Meijs, Loek P. B.] Catharina Hosp, Dept Cardiol, Eindhoven, Netherlands. [Galeotti, Loriano; Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Pueyo, Esther P.; Romero, Daniel] Univ Zaragoza, E-50009 Zaragoza, Spain. [Jennings, Robert B.; Wagner, Galen S.] Duke Univ, Med Ctr, Durham, NC USA. [Ringborn, Michael] Lund Univ, Dept Cardiol, Lund, Sweden. [Ringborn, Michael] Lund Univ, Ctr Integrat Electrocardiol, Lund, Sweden. [Ringborn, Michael] Blekingesjukhuset, Thorac Ctr, Karlskrona, Sweden. [Warren, Stafford G.] Charleston Area Med Ctr, Charleston, WV USA. RP Strauss, DG (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM david.strauss@fda.hhs.gov RI GALEOTTI, LORIANO/N-4240-2014 OI ROMERO PEREZ, DANIEL/0000-0001-5269-9667; GALEOTTI, LORIANO/0000-0002-3200-9080 FU Ram n y Cajal program, Spain [TEC2010-19410]; American Heart Association, Durham, NC; National Heart, Lung, and Blood Institute; Food and Drug Administration's Critical Path Initiative; [HL-23138]; [HL-27416] FX The development of computerized methods to facilitate in accurate data acquisition was previously supported by project TEC2010-19410 and by Ram n y Cajal program (to E. P. Pueyo), Spain. Data collection for the STAFF III dataset was supported by the American Heart Association, Durham, NC, to M. Ringhorn (account 5-21628). The canine experiments were supported by a series of grants from the National Heart, Lung, and Blood Institute. The final grants were HL-23138 and HL-27416. This project was supported in part by the Food and Drug Administration's Critical Path Initiative, and appointments to the Research Participation Program at the Center for Drug Evaluation and Research and Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration. NR 49 TC 3 Z9 3 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL 1 PY 2014 VL 307 IS 1 BP H80 EP H87 DI 10.1152/ajpheart.00419.2013 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA AL1WO UT WOS:000338917200009 PM 24778173 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Naive Pooled-Data Approach for Pharmacokinetic Studies in Pediatrics With a Very Small Sample Size SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE naive pooled analysis; pediatrics; pharmacokinetics; clearance; volume of distribution; half-life ID KWASHIORKOR; INFANTS AB The objective of this study was to evaluate if the pharmacokinetic (PK) parameters (clearance, volumes of distribution, and half-life) from 1 blood sample per subject using naive pooled data (NPD) analysis can be obtained with reasonable accuracy with a very small sample size (n = 5). For this study, 7 drugs were selected from the literature. The PKs of these 7 drugs were studied in pediatrics, and plasma concentrations versus time data for individual subjects from extensive blood sampling were available. For this analysis, only 5 subjects were chosen, and each subject gave 1 blood sample. The estimated PK parameters from NPD analysis were compared with the mean PK parameters obtained from extensive sampling. The result of the study indicated that a fairly accurate estimate of PK parameters can be obtained with 1 blood sample each from a minimum of 5 subjects using NPD analysis. The NPD analysis with sparse-sampling scheme can be useful for PK studies in neonates and very young children, where sample size is small. C1 US FDA, Off Blood Review & Res, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Blood Review & Res, Ctr Biol Evaluat & Res, 1451 Rockville Pike, Rockville, MD 20852 USA. EM iftekhar.mahmood@fda.hhs.gov NR 7 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1075-2765 EI 1536-3686 J9 AM J THER JI Am. J. Ther. PD JUL-AUG PY 2014 VL 21 IS 4 BP 269 EP 274 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AL5JV UT WOS:000339170800016 PM 22713529 ER PT J AU Grim, CJ Kozlova, EV Ponnusamy, D Fitts, EC Sha, J Kirtley, ML van Lier, CJ Tiner, BL Erova, TE Joseph, SJ Read, TD Shak, JR Joseph, SW Singletary, E Felland, T Baze, WB Horneman, AJ Chopra, AK AF Grim, Christopher J. Kozlova, Elena V. Ponnusamy, Duraisamy Fitts, Eric C. Sha, Jian Kirtley, Michelle L. van Lier, Christina J. Tiner, Bethany L. Erova, Tatiana E. Joseph, Sandeep J. Read, Timothy D. Shak, Joshua R. Joseph, Sam W. Singletary, Ed Felland, Tracy Baze, Wallace B. Horneman, Amy J. Chopra, Ashok K. TI Functional Genomic Characterization of Virulence Factors from Necrotizing Fasciitis-Causing Strains of Aeromonas hydrophila SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SECRETION SYSTEM EFFECTOR; INTESTINAL EPITHELIAL-CELLS; N-ACYLHOMOSERINE LACTONES; SOFT-TISSUE INFECTIONS; AERUGINOSA EXOTOXIN-A; IN-VIVO VIRULENCE; PSEUDOMONAS-AERUGINOSA; BIOFILM FORMATION; CYTOTOXIC ENTEROTOXIN; CLINICAL ISOLATE AB The genomes of 10 Aeromonas isolates identified and designated Aeromonas hydrophila WI, Riv3, and NF1 to NF4; A. dhakensis SSU; A. jandaei Riv2; and A. caviae NM22 and NM33 were sequenced and annotated. Isolates NF1 to NF4 were from a patient with necrotizing fasciitis (NF). Two environmental isolates (Riv2 and -3) were from the river water from which the NF patient acquired the infection. While isolates NF2 to NF4 were clonal, NF1 was genetically distinct. Outside the conserved core genomes of these 10 isolates, several unique genomic features were identified. The most virulent strains possessed one of the following four virulence factors or a combination of them: cytotoxic enterotoxin, exotoxin A, and type 3 and 6 secretion system effectors AexU and Hcp. In a septicemic-mouse model, SSU, NF1, and Riv2 were the most virulent, while NF2 was moderately virulent. These data correlated with high motility and biofilm formation by the former three isolates. Conversely, in a mouse model of intramuscular infection, NF2 was much more virulent than NF1. Isolates NF2, SSU, and Riv2 disseminated in high numbers from the muscular tissue to the visceral organs of mice, while NF1 reached the liver and spleen in relatively lower numbers on the basis of colony counting and tracking of bioluminescent strains in real time by in vivo imaging. Histopathologically, degeneration of myofibers with significant infiltration of polymorphonuclear cells due to the highly virulent strains was noted. Functional genomic analysis provided data that allowed us to correlate the highly infectious nature of Aeromonas pathotypes belonging to several different species with virulence signatures and their potential ability to cause NF. C1 [Grim, Christopher J.] US FDA, Laurel, MD USA. [Kozlova, Elena V.; Ponnusamy, Duraisamy; Fitts, Eric C.; Sha, Jian; Kirtley, Michelle L.; van Lier, Christina J.; Tiner, Bethany L.; Erova, Tatiana E.; Chopra, Ashok K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Joseph, Sandeep J.; Read, Timothy D.; Shak, Joshua R.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA. [Joseph, Sam W.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Joseph, Sam W.] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. [Singletary, Ed] Doctors Hosp, Augusta, GA USA. [Felland, Tracy] Mercy Hosp, Janesville, WI USA. [Felland, Tracy] Ctr Trauma, Janesville, WI USA. [Baze, Wallace B.] Univ Texas MD Anderson Canc Ctr, Dept Vet Sci, Bastrop, TX USA. [Horneman, Amy J.] VA Maryland Hlth Care Syst, Pathol & Lab Med Serv, Baltimore, MD USA. RP Chopra, AK (reprint author), Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. EM achopra@utmb.edu FU Leon Bromberg and Robert E. Shope and John S. Dunn Distinguished Chair in Global Health endowments, UTMB FX The financial support provided to A.K.C. through Leon Bromberg and Robert E. Shope and John S. Dunn Distinguished Chair in Global Health endowments, UTMB, is gratefully acknowledged. NR 101 TC 14 Z9 14 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2014 VL 80 IS 14 BP 4162 EP 4183 DI 10.1128/AEM.00486-14 PG 22 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA AK8VN UT WOS:000338706800009 PM 24795370 ER PT J AU Fouad, A Pfefer, TJ Chen, CW Gong, W Agrawal, A Tomlins, PH Woolliams, PD Drezek, RA Chen, Y AF Fouad, Anthony Pfefer, T. Joshua Chen, Chao-Wei Gong, Wei Agrawal, Anant Tomlins, Peter H. Woolliams, Peter D. Drezek, Rebekah A. Chen, Yu TI Variations in optical coherence tomography resolution and uniformity: a multi-system performance comparison SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID POINT-SPREAD FUNCTION; PHANTOM; OCT AB Point spread function (PSF) phantoms based on unstructured distributions of sub-resolution particles in a transparent matrix have been demonstrated as a useful tool for evaluating resolution and its spatial variation across image volumes in optical coherence tomography (OCT) systems. Measurements based on PSF phantoms have the potential to become a standard test method for consistent, objective and quantitative inter-comparison of OCT system performance. Towards this end, we have evaluated three PSF phantoms and investigated their ability to compare the performance of four OCT systems. The phantoms are based on 260-nm-diameter gold nanoshells, 400-nm-diameter iron oxide particles and 1.5-micron-diameter silica particles. The OCT systems included spectral-domain and swept source systems in free-beam geometries as well as a time-domain system in both free-beam and fiberoptic probe geometries. Results indicated that iron oxide particles and gold nanoshells were most effective for measuring spatial variations in the magnitude and shape of PSFs across the image volume. The intensity of individual particles was also used to evaluate spatial variations in signal intensity uniformity. Significant system-to-system differences in resolution and signal intensity and their spatial variation were readily quantified. The phantoms proved useful for identification and characterization of irregularities such as astigmatism. Our multi-system results provide evidence of the practical utility of PSF-phantom-based test methods for quantitative inter-comparison of OCT system resolution and signal uniformity. (C) 2014 Optical Society of America C1 [Fouad, Anthony; Pfefer, T. Joshua; Chen, Chao-Wei; Gong, Wei; Agrawal, Anant] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Fouad, Anthony; Chen, Chao-Wei; Gong, Wei; Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Gong, Wei] Fujian Normal Univ, Coll Photon & Elect Engn, Fuzhou, Fujian, Peoples R China. [Tomlins, Peter H.] Queen Mary Univ London, Barts & London Sch Med & Dent, London E1 1BB, England. [Woolliams, Peter D.] Natl Phys Lab, Funct Mat Grp, Teddington TW11 0LW, Middx, England. [Drezek, Rebekah A.] Rice Univ, Dept Bioengn, Houston, TX USA. RP Fouad, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM joshua.pfefer@fda.hhs.gov FU NSF-FDA Scholar in Residence Program [CBET 1135514] FX This research was funded in part by the NSF-FDA Scholar in Residence Program (CBET 1135514). The authors wish to thank Chia-Pin Liang, Zachary Langley, and Nicholas Woolsey from the University of Maryland for their technical assistance with the OCT hardware and data processing. NR 32 TC 6 Z9 6 U1 0 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD JUL 1 PY 2014 VL 5 IS 7 BP 2066 EP 2081 DI 10.1364/BOE.5.002066 PG 16 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AL2AV UT WOS:000338929100007 PM 25071949 ER PT J AU Ardeshirpour, Y Chernomordik, V Hassan, M Zielinski, R Capala, J Gandjbakhche, A AF Ardeshirpour, Yasaman Chernomordik, Victor Hassan, Moinuddin Zielinski, Rafal Capala, Jacek Gandjbakhche, Amir TI In Vivo Fluorescence Lifetime Imaging for Monitoring the Efficacy of the Cancer Treatment SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN-BREAST-CANCER; AFFIBODY MOLECULES; HER2 EXPRESSION; CONTRAST AGENTS; THERAPY; PET; MOUSE; TRASTUZUMAB; DIAGNOSTICS; SYSTEM AB Purpose: Advances in tumor biology created a foundation for targeted therapy aimed at inactivation of specific molecular mechanisms responsible for cell malignancy. In this paper, we used in vivo fluorescence lifetime imaging with HER2-targeted fluorescent probes as an alternative imaging method to investigate the efficacy of targeted therapy with 17-DMAG (an HSP90 inhibitor) on tumors with high expression of HER2 receptors. Experimental Design: HER2-specific Affibody, conjugated to Alexafluor 750, was injected into nude mice bearing HER2-positive tumor xenograft. The fluorescence lifetime was measured before treatment and monitored after the probe injections at 12 hours after the last treatment dose, when the response to the 17-DMAG therapy was the most pronounced as well as a week after the last treatment when the tumors grew back almost to their pretreatment size. Results: Imaging results showed significant difference between the fluorescence lifetimes at the tumor and the contralateral site (similar to 0.13 ns) in the control group (before treatment) and 7 days after the last treatment when the tumors grew back to their pretreatment dimensions. However, at the time frame that the treatment had its maximum effect (12 hours after the last treatment), the difference between the fluorescence lifetime at the tumor and contralateral site decreased to 0.03 ns. Conclusions: The results showed a good correlation between fluorescence lifetime and the efficacy of the treatment. These findings show that in vivo fluorescence lifetime imaging can be used as a promising molecular imaging tool for monitoring the treatment outcome in preclinical models and potentially in patients. (C)2014 AACR. C1 [Ardeshirpour, Yasaman; Chernomordik, Victor; Hassan, Moinuddin; Gandjbakhche, Amir] NICHHD, NIH, Bethesda, MD 20892 USA. [Hassan, Moinuddin] US FDA, Div Phys, CDRH, Off Sci & Engn Labs, Silver Spring, MD USA. [Zielinski, Rafal; Capala, Jacek] NCI, NIH, Rockville, MD USA. [Zielinski, Rafal] UT MD Anderson Canc Ctr, Houston, TX USA. RP Gandjbakhche, A (reprint author), NICHHD, Sect Analyt & Funct Biophoton, Program Pediat Imaging & Tissue Sci, NIH, Bldg 9,Room 1E-116,9 Mem Dr, Bethesda, MD 20892 USA. EM amir@helix.nih.gov FU National Cancer Institute, NIH; National Institute of Child Health and Human Development, NIH FX This work was supported by the Intramural Research Program of National Cancer Institute, NIH and Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. NR 43 TC 3 Z9 3 U1 3 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2014 VL 20 IS 13 BP 3531 EP 3539 DI 10.1158/1078-0432.CCR-13-1826 PG 9 WC Oncology SC Oncology GA AL1XQ UT WOS:000338920100018 PM 24671949 ER PT J AU Aissa, AF Tryndyak, V de Conti, A Melnyk, S Gomes, TDUH Bianchi, MLP James, SJ Beland, FA Antunes, LMG Pogribny, IP AF Aissa, Alexandre Ferro Tryndyak, Volodymyr de Conti, Aline Melnyk, Stepan Ursula Hermogenes Gomes, Tarsila Daysy Pires Bianchi, Maria Lourdes James, S. Jill Beland, Frederick A. Greggi Antunes, Lusania Maria Pogribny, Igor P. TI Effect of methionine-deficient and methionine-supplemented diets on the hepatic one-carbon and lipid metabolism in mice SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Fatty liver; Homocysteine; Methionine-deficiency; Methionine-supplementation; Mice; Oxidative stress ID ENDOPLASMIC-RETICULUM STRESS; FATTY LIVER-DISEASE; COULOMETRIC ELECTROCHEMICAL DETECTION; PLASMA S-ADENOSYLHOMOCYSTEINE; CYSTATHIONINE BETA-SYNTHASE; OXIDATIVE STRESS; NONALCOHOLIC STEATOHEPATITIS; INTERSTRAIN DIFFERENCES; TRANSCRIPTION FACTORS; DNA HYPOMETHYLATION AB Scope: A compromised nutritional status in methyl-group donors may provoke several molecular alterations triggering the development of nonalcoholic fatty liver disease (NAFLD) in humans and experimental animals. In this study, we investigated a role and the underlying molecular mechanisms of methionine metabolic pathway malfunctions in the pathogenesis of NAFLD. Methods and results: We fed female Swiss albino mice a control (methionine-adequate) diet and two experimental (methionine-deficient or methionine-supplemented) diets for 10 weeks, and the levels of one-carbon metabolites, expression of one-carbon and lipid metabolism genes in the livers were evaluated. We demonstrate that both experimental diets increased hepatic levels of S-adenosyl-L-homocysteine and homocysteine, altered expression of one-carbon and lipid metabolism genes, and caused lipid accumulation, especially in mice fed the methionine-deficient diet. Markers of oxidative and ER stress response were also elevated in the livers of mice fed either diet. Conclusion: Our findings indicate that both dietary methionine deficiency and methionine supplementation can induce molecular abnormalities in the liver associated with the development of NAFLD, including deregulation in lipid and one-carbon metabolic pathways, and induction of oxidative and ER stress. These pathophysiological events may ultimately lead to lipid accumulation in the livers, triggering the development of NAFLD. C1 [Aissa, Alexandre Ferro; Greggi Antunes, Lusania Maria] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, Sao Paulo, Brazil. [Tryndyak, Volodymyr; de Conti, Aline; Beland, Frederick A.; Pogribny, Igor P.] US FDA, Div Biochem Toxicol, NCTR, Jefferson, AR 72079 USA. [Melnyk, Stepan; James, S. Jill] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Ursula Hermogenes Gomes, Tarsila Daysy; Pires Bianchi, Maria Lourdes; Greggi Antunes, Lusania Maria] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Sao Paulo, Brazil. RP Pogribny, IP (reprint author), US FDA, Div Biochem Toxicol, NCTR, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI Antunes, Lusania/B-8040-2012 OI Antunes, Lusania/0000-0002-3079-4388 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2010/01410-0, 2012/10872-2] FX Alexandre Ferro Aissa was sponsored by a fellowship from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Process nos. 2010/01410-0 and 2012/10872-2. NR 51 TC 4 Z9 5 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 EI 1613-4133 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUL PY 2014 VL 58 IS 7 BP 1502 EP 1512 DI 10.1002/mnfr.201300726 PG 11 WC Food Science & Technology SC Food Science & Technology GA AL3CC UT WOS:000339001900011 PM 24827819 ER PT J AU Kasturi, J Brown, AP Brown, P Madhavan, S Prabakar, L Wally, JL AF Kasturi, Jyotsna Brown, Alan P. Brown, Paul Madhavan, Suresh Prabakar, Latha Wally, Jeremy L. TI Interconnectivity of Disparate Nonclinical Data Silos for Drug Discovery and Development SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE informatics; data analysis; drug safety; nonclinical data; interconnectivity; data silos ID QT INTERVAL; PROLONGATION; THERAPY AB Pharmaceutical research and development generates enormous amounts of nonclinical and clinical data related to safety and efficacy, and the ability to manage and utilize these data is critical for discovering and developing new drugs. Information systems exist that store and analyze relationships among seemingly disparate data sets (ie, data silos); however, to fully utilize the potential of these informatics systems, it is necessary to define basic parameters about the data and to develop concepts regarding "interconnectivity," or relationships among disparate data sets. To explore these issues, the Nonclinical Data Interconnectivity Sub-Group was chartered: a component of the Non-Clinical Road-Map and Impacts on Implementation Working Group associated with the US FDA-PhUSE (Pharmaceutical Users Software Exchange) Computational Sciences initiative. As a starting point, the group defined the meaning of data interconnectivity. Nonclinical data types were then identified and challenges and opportunities for interconnectivity explored. Specific-use cases were identified to provide examples of the value for interconnecting data across disciplines or silos. C1 [Kasturi, Jyotsna] Janssen Res & Dev, Raritan, NJ 08869 USA. [Brown, Alan P.] Integrated Nonclin Dev Solut Inc, Ann Arbor, MI USA. [Brown, Paul] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Madhavan, Suresh; Prabakar, Latha] PointCross Life Sci, Bangalore, Karnataka, India. [Wally, Jeremy L.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Kasturi, J (reprint author), Janssen Res & Dev, 1000 Route 202 South, Raritan, NJ 08869 USA. EM jkasturi@its.jnj.com NR 15 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 EI 2168-4804 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD JUL PY 2014 VL 48 IS 4 BP 498 EP 506 DI 10.1177/2168479014531421 PG 9 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA AL2WB UT WOS:000338985200014 ER PT J AU Orecna, M De Paoli, SH Janouskova, O Tegegn, TZ Filipova, M Bonevich, JE Holada, K Simak, J AF Orecna, Martina De Paoli, Silvia H. Janouskova, Olga Tegegn, Tseday Z. Filipova, Marcela Bonevich, John E. Holada, Karel Simak, Jan TI Toxicity of carboxylated carbon nanotubes in endothelial cells is attenuated by stimulation of the autophagic flux with the release of nanomaterial in autophagic vesicles SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Carbon nanotubes; Autophagy; Bafilomycin A1; Exocytosis; Microvesicles ID IN-VITRO; UNCONVENTIONAL SECRETION; MEMBRANE MICROPARTICLES; BLOOD-PLATELETS; CALCIUM-ENTRY; BAFILOMYCIN; DISEASE; PROTEIN; CANCER; DEATH AB Carbon nanotubes (CNTs) exhibit a number of unique properties that make them attractive for various nanomedicine applications including their intravascular use. Therefore, the vascular toxicity of CNTs is a critical safety concern and methods of CNTs toxicity modulation are of great interest. Here, we report that carboxylated multiwalled carbon nanotubes (MWCNTs) induce a decrease in viability of cultured human umbilical vein endothelial cells (HUVECs) associated with the profound accumulation of autophagosomes. This autophagosome accumulation was mTOR kinase independent and was caused by blockade of the autophagic flux rather than by activation of autophagy. Stimulation of the autophagic flux with 1 nmol/L bafilomycin A1 attenuated the cytotoxicity of carboxylated MWCNTs in HUVECs and was associated with the extracellular release of the nanomaterial in autophagic microvesicles. Thus, pharmacological stimulation of the autophagic flux may represent a new method of cytoprotection against toxic effects of nanomaterials. From the Clinical Editor: This study investigates the mechanisms of toxicity of multiwalled carbon nanutubes on human endothelial cells, concluding that pharmacological stimulation of autophagic flux may represent a new method of cytoprotection against the toxic effects of these nanomaterials. Published by Elsevier Inc. C1 [Orecna, Martina; De Paoli, Silvia H.; Tegegn, Tseday Z.; Simak, Jan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Janouskova, Olga; Filipova, Marcela; Holada, Karel] Charles Univ Prague, Fac Med 1, Inst Immunol & Microbiol, Prague, Czech Republic. [Janouskova, Olga] Acad Sci Czech Republic, Inst Macromol Chem, Prague, Czech Republic. [Bonevich, John E.] NIST, Gaithersburg, MD 20899 USA. RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM jan.simak@fda.hhs.gov RI Janouskova, Olga/H-4110-2014 OI Janouskova, Olga/0000-0002-1365-6274 FU Research Participation Program at the Center for Biologics Evaluation and Research; Ministry of Education, Youth and Sports of Czech Republic [LH12014]; Charles University in Prague [SVV260026, PRVOUK-P24/LF1/3, UNCE 204022] FX This project was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through and interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration. In addition, the study was supported in part by the Grant LH12014 from the Ministry of Education, Youth and Sports of Czech Republic. M. F., K. H. and O.J. were supported by projects of Charles University in Prague: SVV260026, PRVOUK-P24/LF1/3 and UNCE 204022, respectively. NR 40 TC 14 Z9 14 U1 1 U2 37 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD JUL PY 2014 VL 10 IS 5 BP 939 EP 948 DI 10.1016/j.nano.2014.02.001 PG 10 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA AK9GS UT WOS:000338736200007 PM 24566271 ER PT J AU Hitchins, VM Clavet, CR Tarver, ME Lucas, AD Brown, J Eydelman, MB AF Hitchins, Victoria M. Clavet, Charles R. Tarver, Michelle E. Lucas, Anne D. Brown, Jennifer Eydelman, Malvina B. TI Response: Interactions of Contact Lenses With a Multipurpose Disinfecting Solution Containing PHMB SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Letter ID STAPHYLOCOCCUS-AUREUS C1 [Hitchins, Victoria M.; Lucas, Anne D.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Clavet, Charles R.] US FDA, Winchester Engn & Analyt Ctr, Winchester, MA USA. [Tarver, Michelle E.; Brown, Jennifer; Eydelman, Malvina B.] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Hitchins, VM (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 EI 1542-233X J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD JUL PY 2014 VL 40 IS 4 BP 266 EP 267 PG 3 WC Ophthalmology SC Ophthalmology GA AK9VR UT WOS:000338777200014 PM 25390552 ER PT J AU Ferlin, KM Prendergast, ME Miller, ML Nguyen, BNB Kaplan, DS Fisher, JP AF Ferlin, Kimberly M. Prendergast, Margaret E. Miller, Makenzie L. Nguyen, Bao-Ngoc B. Kaplan, David S. Fisher, John P. TI Development of a Dynamic Stem Cell Culture Platform for Mesenchymal Stem Cell Adhesion and Evaluation SO MOLECULAR PHARMACEUTICS LA English DT Article DE stem cells; cell adhesion; hydrogel; bioreactor ID IN-VITRO; POLYSTYRENE SURFACES; MATRIX STIFFNESS; HIGH-THROUGHPUT; DRUG DISCOVERY; CANCER CELLS; TGF-BETA; DIFFERENTIATION; SUBSTRATE; TRANSITION AB The importance of providing a physiologically relevant environment for cell culture is well recognized. The combination of proper environmental cues which are provided in vivo by the bloodstream and extracellular matrix must be reproduced to properly examine cell response in vitro, and cannot be recapitulated using traditional culture on polystyrene. Here, we have developed a device, the dynamic stem cell culture platform (DSCCP), consisting of a biomimetic scaffold cultured within the dynamic environment of a perfusion bioreactor. By varying scaffold parameters including stiffness and protein inclusion at the material surface, we found that human mesenchyrnal stem cells (hMSCs) were able to adhere to modified substrates, while still maintaining multipotency. Culture in a perfusion bioreactor showed cell survival and proliferation, particularly on modified substrates. The DSCCP represents a complete platform for cell adhesion and subsequent evaluation, including the response of a cell population to drug treatment. C1 [Ferlin, Kimberly M.; Prendergast, Margaret E.; Miller, Makenzie L.; Nguyen, Bao-Ngoc B.; Fisher, John P.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Kaplan, David S.] US FDA, CDRH, Silver Spring, MD 20993 USA. RP Fisher, JP (reprint author), Univ Maryland, Fischell Dept Bioengn, 3238 Jeong H Kim Engn Bldg 225, College Pk, MD 20742 USA. EM jpfisher@umd.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01 AR061460]; National Science Foundation/Food and Drug Administration Scholar-in-Residence Program [CBET 1238398] FX Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (R01 AR061460) and by the National Science Foundation/Food and Drug Administration Scholar-in-Residence Program (CBET 1238398). The items identified by brand name are the choice of the authors' and are not to be construed as conveying an official endorsement by the U.S. Food and Drug Administration. NR 38 TC 2 Z9 2 U1 2 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUL PY 2014 VL 11 IS 7 BP 2172 EP 2181 DI 10.1021/mp500062n PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AK9LI UT WOS:000338748200026 PM 24620713 ER PT J AU Hunt, RC Simhadri, VL Iandoli, M Sauna, ZE Kimchi-Sarfaty, C AF Hunt, Ryan C. Simhadri, Vijaya L. Iandoli, Matthew Sauna, Zuben E. Kimchi-Sarfaty, Chava TI Exposing synonymous mutations SO TRENDS IN GENETICS LA English DT Review DE synonymous mutation; synonymous single nucleotide polymorphism; codon usage; mRNA structure; translation speed ID EXONIC SPLICING ENHANCERS; SINGLE-NUCLEOTIDE POLYMORPHISM; MICRORNA TARGET PREDICTIONS; RNA SECONDARY STRUCTURE; NONOPTIMAL CODON USAGE; PRE-MESSENGER-RNA; GENE-EXPRESSION; ESCHERICHIA-COLI; PROTEIN EXPRESSION; IN-VIVO AB Synonymous codon changes, which do not alter protein sequence, were previously thought to have no functional consequence. Although this concept has been overturned in recent years, there is no unique mechanism by which these changes exert biological effects. A large repertoire of both experimental and bioinformatic methods has been developed to understand the effects of synonymous variants. Results from this body of work have provided global insights into how biological systems exploit the degeneracy of the genetic code to control gene expression, protein folding efficiency, and the coordinated expression of functionally related gene families. Although it is now clear that synonymous variants are important in a variety of contexts, from human disease to the safety and efficacy of therapeutic proteins, there is no clear consensus on the approaches to identify and validate these changes. Here, we review the diverse methods to understand the effects of synonymous mutations. C1 [Hunt, Ryan C.; Simhadri, Vijaya L.; Iandoli, Matthew; Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Hunt, RC (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. EM ryan.hunt@fda.hhs.gov; zuben.sauna@fda.hhs.gov; chava.kimchi-sarfaty@fda.hhs.gov FU Laboratory of Hemostasis; Center for Biologics Evaluation and Research FX We thank Nobuko Katagiri, CBER/FDA for expert assistance with mRNA folding tools and Avi Kimchi, NCBI, NIH for editorial assistance and insightful discussions. This work was supported by funds from the Laboratory of Hemostasis, Center for Biologics Evaluation and Research (C.K-S. and Z.E.S.). NR 142 TC 48 Z9 48 U1 6 U2 49 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUL PY 2014 VL 30 IS 7 BP 308 EP 321 DI 10.1016/j.tig.2014.04.006 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA AL1VZ UT WOS:000338915700005 PM 24954581 ER PT J AU Shankar, G Arkin, S Cocea, L Devanarayan, V Kirshner, S Kromminga, A Quarmby, V Richards, S Schneider, CK Subramanyam, M Swanson, S Verthelyi, D Yim, S AF Shankar, G. Arkin, S. Cocea, L. Devanarayan, V. Kirshner, S. Kromminga, A. Quarmby, V. Richards, S. Schneider, C. K. Subramanyam, M. Swanson, S. Verthelyi, D. Yim, S. TI Assessment and Reporting of the Clinical Immunogenicity of Therapeutic Proteins and Peptides-Harmonized Terminology and Tactical Recommendations SO AAPS JOURNAL LA English DT Article DE anti-drug antibody; clinical relevance; harmonization ID RISK-BASED APPROACH; ANTIBODY IMMUNE-RESPONSES; RED-CELL APLASIA; BIOTECHNOLOGY PRODUCTS; BIOLOGICAL THERAPEUTICS; HOST ANTIBODIES; ADALIMUMAB; ASSAYS; CONSEQUENCES; INTERFERENCE AB Immunogenicity is a significant concern for biologic drugs as it can affect both safety and efficacy. To date, the descriptions of product immunogenicity have varied not only due to different degrees of understanding of product immunogenicity at the time of licensing but also due to an evolving lexicon that has generated some confusion in the field. In recent years, there has been growing consensus regarding the data needed to assess product immunogenicity. Harmonization of the strategy for the elucidation of product immunogenicity by drug developers, as well as the use of defined common terminology, can benefit medical practitioners, health regulatory agencies, and ultimately the patients. Clearly, understanding the incidence, kinetics and magnitude of anti-drug antibody (ADA), its neutralizing ability, cross-reactivity with endogenous molecules or other marketed biologic drugs, and related clinical impact may enhance clinical management of patients treated with biologic drugs. To that end, the authors present terms and definitions for describing and analyzing clinical immunogenicity data and suggest approaches to data presentation, emphasizing associations of ADA development with pharmacokinetics, efficacy, and safety that are necessary to assess the clinical relevance of immunogenicity. C1 [Shankar, G.] Janssen Res & Dev LLC Johnson & Johnson, Spring House, PA 19477 USA. [Arkin, S.] Pfizer Worldwide Res & Dev, Cambridge, MA USA. [Cocea, L.] Hlth Canada, CERB Clin Evaluat Div, Ottawa, ON K1A 0L2, Canada. [Devanarayan, V.] AbbVie Inc, Chicago, IL USA. [Kirshner, S.; Verthelyi, D.] US FDA, CDER Off Therapeut Prot, Rockville, MD 20857 USA. [Kromminga, A.] IPM Biotech GmbH, Hamburg, Germany. [Quarmby, V.] Genentech Inc, San Francisco, CA 94080 USA. [Richards, S.] Sanofi, Framingham, MA USA. [Schneider, C. K.] Danish Natl Hlth & Med Author, dannat, Copenhagen, Denmark. [Schneider, C. K.] Twincore Ctr Infect Res, Hannover, Germany. [Subramanyam, M.] Biogen Idec Inc, Cambridge, MA USA. [Swanson, S.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Yim, S.] US FDA, Div Pulm Allergy & Rheumatol Prod, Rockville, MD 20857 USA. RP Shankar, G (reprint author), Janssen Res & Dev LLC Johnson & Johnson, 1400 McKean Rd,POB 776, Spring House, PA 19477 USA. EM Gshanka3@its.jnj.com FU Therapeutic Protein Immunogenicity Focus Group (TPIFG) of the BIOTEC Section, American Association of Pharmaceutical Scientists (AAPS) FX This work was sponsored by The Therapeutic Protein Immunogenicity Focus Group (TPIFG) of the BIOTEC Section, American Association of Pharmaceutical Scientists (AAPS). A global physician survey was conducted by TPIFG in 2010 and 2011 to assess the viewpoints and needs of medical practitioners relative to immunogenicity. Survey results and a call for the harmonization of terminology and the analysis and reporting of clinical immunogenicity were presented at the European Immunogenicity Platform (EIP) Symposium in December 2010 (Gent, Belgium) and at an Open Forum of the AAPS National Biotechnology Conference (NBC) in May 2011 (San Francisco, USA). Draft definitions and work-in-progress data presentation tactics were presented at the EIP symposia in February 2012 (Copenhagen, Denmark) and February 2013 (Munich, Germany) and at AAPS-NBC conventions in May 2012 and May 2013 (San Diego, USA). Finally, a draft manuscript was posted on the AAPS website for public feedback. The authors thank all those who provided feedback, which was considered during the finalization of this manuscript. During the preparation of this manuscript, our recommended terminology, definitions, and approaches for ADA characterization were shared with the ABIRISK(Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) consortium, which agreed to adopt them. ABIRISK is a project of the Innovative Medicines Initiative (IMI), a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA), and aims to conduct immunogenicity studies of several biologic drugs, which will be used to develop a database comprising their evaluations of factors underlying immunogenicity and to generate tools for determining how individual patients are likely to respond. NR 46 TC 42 Z9 43 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JUL PY 2014 VL 16 IS 4 BP 658 EP 673 DI 10.1208/s12248-014-9599-2 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK3PP UT WOS:000338337400005 PM 24764037 ER PT J AU Finch, G Havel, H Analoui, M Barton, RW Diwan, AR Hennessy, M Reddy, V Sadrieh, N Tamarkin, L Wolfgang, M Yerxa, B Zolnik, B Liu, M AF Finch, Gregory Havel, Henry Analoui, Mostafa Barton, Randall W. Diwan, Anil R. Hennessy, Meliessa Reddy, Vijayapal Sadrieh, Nakissa Tamarkin, Lawrence Wolfgang, Marc Yerxa, Benjamin Zolnik, Banu Liu, Man TI Nanomedicine Drug Development: A Scientific Symposium Entitled "Charting a Roadmap to Commercialization" SO AAPS JOURNAL LA English DT Article ID CANCER; NANOPARTICLES; PHARMACOKINETICS; BIODISTRIBUTION; NANOTECHNOLOGY; CLEARANCE; DELIVERY; TRIAL AB The use of nanotechnology in medicine holds great promise for revolutionizing a variety of therapies. The past decade witnessed dramatic advancements in scientific research in nanomedicines, although significant challenges still exist in nanomedicine design, characterization, development, and manufacturing. In March 2013, a two-day symposium "Nanomedicines: Charting a Roadmap to Commercialization," sponsored and organized by the Nanomedicines Alliance, was held to facilitate better understanding of the current science and investigative approaches and to identify and discuss challenges and knowledge gaps in nanomedicine development programs. The symposium provided a forum for constructive dialogue among key stakeholders in five distinct areas: nanomedicine design, preclinical pharmacology, toxicology, CMC (chemistry, manufacturing, and control), and clinical development. In this meeting synopsis, we highlight key points from plenary presentations and focus on discussions and recommendations from breakout sessions of the symposium. C1 [Finch, Gregory] Pfizer Inc, Groton, CT 06340 USA. [Havel, Henry; Reddy, Vijayapal] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Analoui, Mostafa] Livingston Secur, New York, NY USA. [Barton, Randall W.; Diwan, Anil R.] NanoViricides, West Haven, CT USA. [Hennessy, Meliessa; Wolfgang, Marc] Cerulean Pharma Inc, Cambridge, MA USA. [Sadrieh, Nakissa; Zolnik, Banu] US FDA, Silver Spring, MD USA. [Tamarkin, Lawrence] CytImmune Sci Inc, Rockville, MD USA. [Yerxa, Benjamin] Liquidia Technol Inc, Morrisville, NC USA. [Liu, Man] Drinker Biddle & Reath LLP, Washington, DC 20005 USA. RP Liu, M (reprint author), Drinker Biddle & Reath LLP, 1500 K St NW, Washington, DC 20005 USA. EM Maggie.Liu@dbr.com NR 20 TC 6 Z9 6 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JUL PY 2014 VL 16 IS 4 BP 698 EP 704 DI 10.1208/s12248-014-9608-5 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK3PP UT WOS:000338337400009 PM 24821054 ER PT J AU Yu, LX Amidon, G Khan, MA Hoag, SW Polli, J Raju, GK Woodcock, J AF Yu, Lawrence X. Amidon, Gregory Khan, Mansoor A. Hoag, Stephen W. Polli, James Raju, G. K. Woodcock, Janet TI Understanding Pharmaceutical Quality by Design SO AAPS JOURNAL LA English DT Review DE control strategy; critical quality attributes; pharmaceutical quality by design; process understanding; product understanding ID SOLID DISPERSION FORMULATION; VARIABLES; PRODUCT; TABLET; IMPACT; QBD AB This review further clarifies the concept of pharmaceutical quality by design (QbD) and describes its objectives. QbD elements include the following: (1) a quality target product profile (QTPP) that identifies the critical quality attributes (CQAs) of the drug product; (2) product design and understanding including identification of critical material attributes (CMAs); (3) process design and understanding including identification of critical process parameters (CPPs), linking CMAs and CPPs to CQAs; (4) a control strategy that includes specifications for the drug substance(s), excipient(s), and drug product as well as controls for each step of the manufacturing process; and (5) process capability and continual improvement. QbD tools and studies include prior knowledge, risk assessment, mechanistic models, design of experiments (DoE) and data analysis, and process analytical technology (PAT). As the pharmaceutical industry moves toward the implementation of pharmaceutical QbD, a common terminology, understanding of concepts and expectations are necessary. This understanding will facilitate better communication between those involved in risk-based drug development and drug application review. C1 [Yu, Lawrence X.; Khan, Mansoor A.; Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Amidon, Gregory] Univ Michigan, Ann Arbor, MI 48109 USA. [Hoag, Stephen W.; Polli, James] Univ Maryland, Baltimore, MD 21201 USA. [Raju, G. K.] MIT, Cambridge, MA 02139 USA. [Raju, G. K.] Light Pharm Inc, Cambridge, MA 02142 USA. RP Yu, LX (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM lawrence.yu@fda.hhs.gov NR 43 TC 51 Z9 52 U1 19 U2 96 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JUL PY 2014 VL 16 IS 4 BP 771 EP 783 DI 10.1208/s12248-014-9598-3 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK3PP UT WOS:000338337400016 PM 24854893 ER PT J AU Chen, MJ Tung, CW Shi, Q Guo, L Shi, LM Fang, H Borlak, J Tong, WD AF Chen, Minjun Tung, Chun-Wei Shi, Qiang Guo, Lei Shi, Leming Fang, Hong Borlak, Jurgen Tong, Weida TI A testing strategy to predict risk for drug-induced liver injury in humans using high-content screen assays and the 'rule-of-two' model SO ARCHIVES OF TOXICOLOGY LA English DT Article DE Drug-induced liver injury; DILI; High-content screening assay; Primary rat hepatocytes; Drug safety assessment ID IN-VITRO APPROACH; HUMAN PHARMACOKINETICS; HEPATOTOXICITY; TOXICITY; CYTOTOXICITY; DISCOVERY; SCIENCE AB Drug-induced liver injury (DILI) is a major cause of drug failures in both the preclinical and clinical phase. Consequently, improving prediction of DILI at an early stage of drug discovery will reduce the potential failures in the subsequent drug development program. In this regard, high-content screening (HCS) assays are considered as a promising strategy for the study of DILI; however, the predictive performance of HCS assays is frequently insufficient. In the present study, a new testing strategy was developed to improve DILI prediction by employing in vitro assays that was combined with the RO2 model (i.e., 'rule-of-two' defined by daily dose a parts per thousand yen100 mg/day & logP a parts per thousand yen3). The RO2 model was derived from the observation that high daily doses and lipophilicity of an oral medication were associated with significant DILI risk in humans. In the developed testing strategy, the RO2 model was used for the rational selection of candidates for HCS assays, and only the negatives predicted by the RO2 model were further investigated by HCS. Subsequently, the effects of drug treatment on cell loss, nuclear size, DNA damage/fragmentation, apoptosis, lysosomal mass, mitochondrial membrane potential, and steatosis were studied in cultures of primary rat hepatocytes. Using a set of 70 drugs with clear evidence of clinically relevant DILI, the testing strategy improved the accuracies by 10 % and reduced the number of drugs requiring experimental assessment by approximately 20 %, as compared to the HCS assay alone. Moreover, the testing strategy was further validated by including published data (Cosgrove et al. in Toxicol Appl Pharmacol 237:317-330, 2009) on drug-cytokine-induced hepatotoxicity, which improved the accuracies by 7 %. Taken collectively, the proposed testing strategy can significantly improve the prediction of in vitro assays for detecting DILI liability in an early drug discovery phase. C1 [Chen, Minjun; Tung, Chun-Wei; Tong, Weida] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Tung, Chun-Wei] Kaohsiung Med Univ, Sch Pharm, Kaohsiung, Taiwan. [Shi, Qiang] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Guo, Lei] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Shi, Leming] Fudan Univ, Sch Pharm, Shanghai 200433, Peoples R China. [Fang, Hong] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Borlak, Jurgen] Hannover Med Sch, Ctr Pharmacol & Toxicol, Hannover, Germany. RP Tong, WD (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov RI Tung, Chun-Wei/B-3749-2008 OI Tung, Chun-Wei/0000-0003-3011-8440 FU German Federal Ministry for Education and Research as part of the Virtual Liver Network initiative [031 6154]; US FDA Oak Ridge Institute for Science and Education (ORISE) FX Jurgen Borlak receives funding from the German Federal Ministry for Education and Research as part of the Virtual Liver Network initiative (Grant No. 031 6154). Jurgen Borlak also gratefully acknowledges a stipend from the US FDA Oak Ridge Institute for Science and Education (ORISE). We thank Robin Stingley, Donna Mendrick, Frederick Beland, Jie Zhang, and Yuping Wang for their comments and English editing. NR 37 TC 18 Z9 19 U1 6 U2 24 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5761 EI 1432-0738 J9 ARCH TOXICOL JI Arch. Toxicol. PD JUL PY 2014 VL 88 IS 7 BP 1439 EP 1449 DI 10.1007/s00204-014-1276-9 PG 11 WC Toxicology SC Toxicology GA AK2XL UT WOS:000338283400009 PM 24958025 ER PT J AU Ludeke, CHM Fischer, M LaFon, P Cooper, K Jones, JL AF Luedeke, Catharina H. M. Fischer, Markus LaFon, Patti Cooper, Kara Jones, Jessica L. TI Suitability of the Molecular Subtyping Methods Intergenic Spacer Region, Direct Genome Restriction Analysis, and Pulsed-Field Gel Electrophoresis for Clinical and Environmental Vibrio parahaemolyticus Isolates SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; TYPING METHODS; UNITED-STATES; STRAINS; VULNIFICUS; PROTOCOL; EPIDEMIOLOGY; VALIDATION; CHOLERAE; CHILE AB Vibrio parahaemolyticus is the leading cause of infectious illness associated with seafood consumption in the United States. Molecular fingerprinting of strains has become a valuable research tool for understanding this pathogen. However, there are many subtyping methods available and little information on how they compare to one another. For this study, a collection of 67 oyster and 77 clinical V. parahaemolyticus isolates were analyzed by three subtyping methods-intergenic spacer region (ISR-1), direct genome restriction analysis (DGREA), and pulsed-field gel electrophoresis (PFGE)-to determine the utility of these methods for discriminatory subtyping. ISR-1 analysis, run as previously described, provided the lowest discrimination of all the methods (discriminatory index [DI] = 0.8665). However, using a broader analytical range than previously reported, ISR-1 clustered isolates based on origin (oyster versus clinical) and had a DI = 0.9986. DGREA provided a DI = 0.9993-0.9995, but did not consistently cluster the isolates by any identifiable characteristics (origin, serotype, or virulence genotype) and similar to 15% of isolates were untypeable by this method. PFGE provided a DI = 0.9998 when using the combined pattern analysis of both restriction enzymes, SfiI and NotI. This analysis was more discriminatory than using either enzyme pattern alone and primarily grouped isolates by serotype, regardless of strain origin (clinical or oyster) or presence of currently accepted virulence markers. These results indicate that PFGE and ISR-1 are more reliable methods for subtyping V. parahemolyticus, rather than DGREA. Additionally, ISR-1 may provide an indication of pathogenic potential; however, more detailed studies are needed. These data highlight the diversity within V. parahaemolyticus and the need for appropriate selection of subtyping methods depending on the study objectives. C1 [Luedeke, Catharina H. M.; Jones, Jessica L.] US FDA, Gulf Coast Seafood Lab, Div Seafood & Technol, Dauphin Isl, AL 36528 USA. [Luedeke, Catharina H. M.; Fischer, Markus] Univ Hamburg, Hamburg Sch Food Sci, Hamburg, Germany. [LaFon, Patti; Cooper, Kara] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Ludeke, CHM (reprint author), US FDA, Gulf Coast Seafood Lab, Div Seafood & Technol, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM catharina.luedeke@fda.hhs.gov; Jessica.Jones@fda.hhs.gov FU FDA FX This project was supported by an appointment to the Research Fellowship Program for the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Associated Universities through a contract with the FDA. NR 27 TC 4 Z9 4 U1 0 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 EI 1556-7125 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD JUL PY 2014 VL 11 IS 7 BP 520 EP 528 DI 10.1089/fpd.2013.1728 PG 9 WC Food Science & Technology SC Food Science & Technology GA AK1PG UT WOS:000338186600004 PM 24799175 ER PT J AU Reynnells, R Ingram, DT Roberts, C Stonebraker, R Handy, ET Felton, G Vinyard, BT Millner, PD Sharma, M AF Reynnells, Russell Ingram, David T. Roberts, Cheryl Stonebraker, Richard Handy, Eric T. Felton, Gary Vinyard, Bryan T. Millner, Patricia D. Sharma, Manan TI Comparison of U.S. Environmental Protection Agency and U.S. Composting Council Microbial Detection Methods in Finished Compost and Regrowth Potential of Salmonella spp. and Escherichia coli O157:H7 in Finished Compost SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID INDIGENOUS MICROORGANISMS; PATHOGENIC BACTERIA; UNITED-STATES; SEWAGE-SLUDGE; BIOSOLIDS; GROWTH; SUPPRESSION; SURVIVAL; REGULATIONS AB Bacterial pathogens may survive and regrow in finished compost due to incomplete thermal inactivation during or recontamination after composting. Twenty-nine finished composts were obtained from 19 U. S. states and were separated into three broad feedstock categories: biosolids (n = 10), manure (n = 4), and yard waste (n = 15). Three replicates of each compost were inoculated with approximate to 1-2 log CFU/g of nonpathogenic Escherichia coli, Salmonella spp., and E. coli O157:H7. The U. S. Environmental Protection Agency's (EPA) protocols and U. S. Composting Council's (USCC) Test Methods for the Examination of Composting and Compost (TMECC) were compared to determine which method recovered higher percentages of inoculated E. coli (representing fecal coliforms) and Salmonella spp. from 400-g samples of finished composts. Populations of Salmonella spp. and E. coli O157: H7 were determined over 3 days while stored at 25 degrees C and compared to physicochemical parameters to predict their respective regrowth potentials. EPA Method 1680 recovered significantly (p = 0.0003) more inoculated E. coli (68.7%) than TMECC 07.01 (48.1%) due to the EPA method using more compost in the initial homogenate, larger transfer dilutions, and a larger most probable number scheme compared to TMECC 07.01. The recoveries of inoculated Salmonella spp. by Environmental Protection Agency Method 1682 (89.1%) and TMECC 07.02 (72.4%) were not statistically significant (p = 0.44). The statistically similar recovery percentages may be explained by the use of a nonselective pre-enrichment step used in both methods. No physicochemical parameter (C:N, moisture content, total organic carbon) was able to serve as a sole predictor of regrowth of Salmonella spp. or E. coli O157:H7 in finished compost. However, statistical analysis revealed that the C:N ratio, total organic carbon, and moisture content all contributed to pathogen regrowth potential in finished composts. It is recommended that the USCC modify TMECC protocols to test larger amounts of compost in the initial homogenate to facilitate greater recovery of target organisms. C1 [Reynnells, Russell; Roberts, Cheryl; Stonebraker, Richard; Handy, Eric T.; Millner, Patricia D.; Sharma, Manan] ARS, Environm Microbial & Food Safety Lab, Henry A Wallace Beltsville Area Res Ctr, USDA, Beltsville, MD 20705 USA. [Ingram, David T.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Felton, Gary] Univ Maryland, Environm Sci & Technol Dept, College Pk, MD 20742 USA. [Vinyard, Bryan T.] ARS, Henry A Wallace Beltsville Area Res Ctr, Biometr Consulting Serv, USDA, Beltsville, MD 20705 USA. RP Sharma, M (reprint author), ARS, Environm Microbial & Food Safety Lab, Henry A Wallace Beltsville Area Res Ctr, USDA, Bldg 201,10300 Baltimore Ave, Beltsville, MD 20705 USA. EM manan.sharma@ars.usda.gov FU Center for Produce Safety; USDA-ARS FX The authors thank Dr. Yang Yang, Dr. Wilbert Long, Rishi Banerjee, Hannah Birnbaum, Mary Theresa Callahan, Nathalia Cancel Villamil, Cianni Dudley, Sean Ferguson, Natalia Macarisin, Isaac Onigbinde, and Ajay Singh for contributions to this project. Funding was provided by the Center for Produce Safety grant "Validation of testing methods for the detection and quantification of Escherichia coli O157:H7, Salmonella spp., fecal coliforms and non-pathogenic Escherichia coli in compost'' and the USDA-ARS "Microbial Ecology & Safety of Fresh on-Farm Organically Grown Produce'' project. NR 22 TC 5 Z9 5 U1 1 U2 24 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 EI 1556-7125 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD JUL PY 2014 VL 11 IS 7 BP 555 EP 567 DI 10.1089/fpd.2013.1698 PG 13 WC Food Science & Technology SC Food Science & Technology GA AK1PG UT WOS:000338186600009 PM 24814265 ER PT J AU Duncan, R AF Duncan, Robert TI Advancing Molecular Diagnostics for Trypanosomatid Parasites COMMENT SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material ID REAL-TIME PCR; HUMAN AFRICAN TRYPANOSOMIASIS; SENSITIVE DETECTION; MINICIRCLE DNA; CHAGAS-DISEASE; BLOOD-SAMPLES; LEISHMANIA; GENOME; ASSAY; CRUZI C1 [Duncan, Robert] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Duncan, R (reprint author), US FDA, CBER, Bldg 29B,Rm 5NN08,8800 Rockville Pike HFM310, Bethesda, MD 20892 USA. EM robert.duncan@fda.hhs.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 19 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD JUL PY 2014 VL 16 IS 4 BP 379 EP 381 DI 10.1016/j.jmoldx.2014.04.001 PG 3 WC Pathology SC Pathology GA AK4OM UT WOS:000338404000001 PM 24815378 ER PT J AU Knolhoff, AM Callahan, JH Croley, TR AF Knolhoff, Ann M. Callahan, John H. Croley, Timothy R. TI Mass Accuracy and Isotopic Abundance Measurements for HR-MS Instrumentation: Capabilities for Non-Targeted Analyses SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article DE Non-targeted analysis; Mass accuracy; Relative isotopic abundance; High-resolution mass spectrometry ID ELEMENTAL COMPOSITIONS; SPECTROMETRY AB The development of automated non-targeted workflows for small molecule analyses is highly desirable in many areas of research and diagnostics. Sufficient mass and chromatographic resolution is necessary for the detectability of compounds and subsequent componentization and interpretation of ions. The mass accuracy and relative isotopic abundance are critical in correct molecular formulae generation for unknown compounds. While high-resolution instrumentation provides accurate mass information, sample complexity can greatly influence data quality and the measurement of compounds of interest. Two high-resolution instruments, an Orbitrap and a Q-TOF, were evaluated for mass accuracy and relative isotopic abundance with various concentrations of a standard mixture in four complex sample matrices. The overall average +/- standard deviation of the mass accuracy was 1.06 +/- 0.76 ppm and 1.62 +/- 1.88 ppm for the Orbitrap and the Q-TOF, respectively; however, individual measurements were +/- 5 ppm for the Orbitrap and greater than 10 ppm for the Q-TOF. Relative isotopic abundance measurements for A + 1 were within 5% of the theoretical value if the intensity of the monoisotopic peak was greater than 1E7 for the Orbitrap and 1E5 for the Q-TOF, where an increase in error is observed with a decrease in intensity. Furthermore, complicating factors were found in the data that would impact automated data analysis strategies, including coeluting species that interfere with detectability and relative isotopic abundance measurements. The implications of these findings will be discussed with an emphasis on reasonable expectations from these instruments, guidelines for experimental workflows, data analysis considerations, and software design for non-targeted analyses. C1 [Knolhoff, Ann M.; Callahan, John H.; Croley, Timothy R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Knolhoff, AM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 707, College Pk, MD 20740 USA. EM Ann.Knolhoff@fda.hhs.gov NR 20 TC 13 Z9 13 U1 4 U2 36 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 EI 1879-1123 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JUL PY 2014 VL 25 IS 7 BP 1285 EP 1294 DI 10.1007/s13361-014-0880-5 PG 10 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA AK1RG UT WOS:000338192700020 PM 24729191 ER PT J AU Khozin, S Blumenthal, GM Jiang, XP He, K Boyd, K Murgo, A Justice, R Keegan, P Pazdur, R AF Khozin, Sean Blumenthal, Gideon M. Jiang, Xiaoping He, Kun Boyd, Karen Murgo, Anthony Justice, Robert Keegan, Patricia Pazdur, Richard TI US Food and Drug Administration Approval Summary: Erlotinib for the First-Line Treatment of Metastatic Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 (L858R) Substitution Mutations SO ONCOLOGIST LA English DT Article DE Erlotinib; EGFR mutations; Lung cancer; FDA ID VINORELBINE PLUS CISPLATIN; PHASE-III TRIAL; RANDOMIZED-TRIAL; EGFR MUTATIONS; OPEN-LABEL; CHEMOTHERAPY; GEFITINIB; CARBOPLATIN; PACLITAXEL; GEMCITABINE AB On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This indication for erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche Molecular Systems, Inc., Basel, Switzerland, http://www.molecular.roche.com), a companion diagnostic test for patient selection. The approval was based on clinically important improvements in progression-free survival (PFS) and objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open label trial enrolling 174 patients with metastatic NSCLC whose tumors had EGFR mutations as determined by a laboratory-developed test. Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum-based doublet chemotherapy. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p < .001) and ORR (65% vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2 months in the erlotinib and chemotherapy arms, respectively. There was no difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and 19.5 months in the erlotinib and chemotherapy arms, respectively. The most frequent (>= 30%) adverse reactions in the erlotinib-treated patients were rash, diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent (>= 5%) grade 3 and 4 adverse reactions were rash and diarrhea. C1 [Khozin, Sean; Blumenthal, Gideon M.; Jiang, Xiaoping; He, Kun; Boyd, Karen; Murgo, Anthony; Justice, Robert; Keegan, Patricia; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Khozin, S (reprint author), US FDA, WhiteOak Campus,10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM sean.khozin@fda.hhs.gov NR 23 TC 28 Z9 31 U1 0 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUL PY 2014 VL 19 IS 7 BP 774 EP 779 DI 10.1634/theoncologist.2014-0089 PG 6 WC Oncology SC Oncology GA AK1QM UT WOS:000338190600014 PM 24868098 ER PT J AU Reppas, C Friedel, HD Barker, AR Buhse, LF Cecil, TL Keitel, S Kraemer, J Morris, JM Shah, VP Stickelmeyer, MP Yomota, C Brown, CK AF Reppas, Christos Friedel, Horst-Dieter Barker, Amy R. Buhse, Lucinda F. Cecil, Todd L. Keitel, Susanne Kraemer, Johannes Morris, J. Michael Shah, Vinod P. Stickelmeyer, Mary P. Yomota, Chikako Brown, Cynthia K. TI Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms-Workshop Report SO PHARMACEUTICAL RESEARCH LA English DT Article DE biorelevant; dissolution; in vitro testing; oral dosage forms; quality control ID POORLY SOLUBLE DRUGS; SMALL-INTESTINE; WEAK BASES; DISSOLUTION; DISINTEGRATION; PRECIPITATION; TABLETS; SYSTEM; FORMULATION; SIMULATION AB Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic. C1 [Reppas, Christos] Univ Athens, Panepistimiopolis, Greece. [Friedel, Horst-Dieter] Bayer Pharma Aktiengesell, Berlin, Germany. [Barker, Amy R.; Stickelmeyer, Mary P.] Eli Lilly & Co, Indianapolis, IN 46225 USA. [Buhse, Lucinda F.] US FDA, CDER, OPS, St Louis, MO USA. [Cecil, Todd L.] US Pharmacopoeia, Rockville, MD USA. [Keitel, Susanne] EDQM, Strasbourg, France. [Kraemer, Johannes] PHAST, Homburg, Germany. [Morris, J. Michael] Irish Med Board, Dublin, Ireland. [Shah, Vinod P.] FIP Regulatory Sci Special Interest Grp Chair, The Hague, Netherlands. [Yomota, Chikako] Natl Inst Hlth Sci, Tokyo, Japan. [Brown, Cynthia K.] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46225 USA. RP Brown, CK (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, DC 3511, Indianapolis, IN 46225 USA. EM Brownck@lilly.com NR 42 TC 4 Z9 4 U1 1 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 EI 1573-904X J9 PHARM RES-DORDR JI Pharm. Res. PD JUL PY 2014 VL 31 IS 7 BP 1867 EP 1876 DI 10.1007/s11095-014-1348-9 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA AK2UN UT WOS:000338275100022 PM 24643933 ER PT J AU Szakal, C Tsytsikova, L Carlander, D Duncan, TV AF Szakal, Christopher Tsytsikova, Lyubov Carlander, David Duncan, Timothy V. TI Measurement Methods for the Oral Uptake of Engineered Nanomaterials from Human Dietary Sources: Summary and Outlook SO COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY LA English DT Review DE characterization; detection; food safety; measurement methods; nanomaterials; nanotechnology; nanotoxicology ID PLASMA-MASS SPECTROMETRY; AMBIENT CONDITIONS; FOOD; NANOPARTICLES; SILVER; ENVIRONMENT; IONIZATION; CHALLENGES; MICROSCOPY; CELLS AB This article is one of a series of 4 that report on a task of the NanoRelease Food Additive (NRFA) project of the International. Life Science Institute Center for Risk Science Innovation and Application. The project aims are to identify, evaluate, and develop methods that are needed to confidently detect, characterize, and quantify intentionally produced engineered nanomaterials (ENMs) released from food along the alimentary tract. This particular article offers an overview of the NRFA project, describing the project scope and goals, as well as the strategy by which the task group sought to achieve these goals. A condensed description of the general challenge of detecting ENMs in foods and a brief review of available and emerging methods for ENM detection is provided here, paying particular attention to the kind of information that might be desired from an analysis and the strengths and weaknesses of the various approaches that might be used to attain this information. The article concludes with an executive summary of the task group's broad findings related to the 3 topic areas, which are covered in more detail in 3 subsequent articles in this series. The end result is a thorough evaluation of the state of ENM measurement science specifically as it applies to oral uptake of ENMs from human dietary sources. C1 [Szakal, Christopher] NIST, Mat Measurement Sci Div, Gaithersburg, MD 20899 USA. [Tsytsikova, Lyubov] ILSI Res Fdn, Ctr Risk Sci Innovat & Applicat, Washington, DC 20005 USA. [Carlander, David] Nanotechnol Ind Assoc, B-1050 Brussels, Belgium. [Duncan, Timothy V.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60516 USA. RP Duncan, TV (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60516 USA. EM timothy.duncan@fda.hhs.gov RI Geracitano, Laura/E-6926-2013 FU Pew Charitable Trusts; US Food and Drug Administration, Health Canada, ILSI North America; Coca-Cola Company; Illinois Inst. of Technology's Inst. for Food Safety and Health; ILSI Research Foundation; USDA Natl. Research Initiative Agriculture and Food Research Initiative; US Environmental Protection Agency; Natl. Science Foundation FX The authors of this report are grateful to the following individuals for their expert input and support for this effort (alphabetically listed): Maurizio Avella, Joe Hotchkiss, Anil Patri, Ruud Peters, Jonathan Powell, Vicki Stone, Scott Thurmond, Jim Waldman, Stefan Weigel, and Jun Jie Yin. Experts were convened and initial framing concepts were developed for this article by the NanoRelease Food Additive Steering Committee (http://www.ilsi.org/ResearchFoundation/RSIA/Pages/FoodAdditiveSteeringC ommittee.aspx and http://www.ilsi.org/ResearchFoundation/RSIA/Pages/NRFA_TaskGroup1.aspx), which operates as an independent public-private partnership. Project management and editing support were provided to the NanoRelease project experts by Richard Canady, Christina West, Molly Bloom, and Elyse Lee of the Center for Risk Science Innovation and Application, ILSI Research Foundation. This phase of the project was funded by the Pew Charitable Trusts, the US Food and Drug Administration, Health Canada, ILSI North America, the Coca-Cola Company, the Illinois Inst. of Technology's Inst. for Food Safety and Health, and the ILSI Research Foundation. Substantial in-kind support was provided by the Nanotechnology Industries Assoc. Furthermore, this material is partly based upon work supported by the USDA Natl. Research Initiative Agriculture and Food Research Initiative, the US Environmental Protection Agency, and the Natl. Science Foundation. NR 35 TC 8 Z9 8 U1 1 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1541-4337 J9 COMPR REV FOOD SCI F JI Compr. Rev. Food. Sci. Food Saf. PD JUL PY 2014 VL 13 IS 4 BP 669 EP 678 DI 10.1111/1541-4337.12080 PG 10 WC Food Science & Technology SC Food Science & Technology GA AJ9LH UT WOS:000338031400017 ER PT J AU Noonan, GO Whelton, AJ Carlander, D Duncan, TV AF Noonan, Gregory O. Whelton, Andrew J. Carlander, David Duncan, Timothy V. TI Measurement Methods to Evaluate Engineered Nanomaterial Release from Food Contact Materials SO COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY LA English DT Review DE characterization; detection; food contact materials; food safety; measurement methods; migration; nanotechnology; release ID SILVER ION RELEASE; SPOILAGE-RELATED MICROFLORA; NANOCOMPOSITE FILMS; CARBON NANOTUBES; ABSORBENT PADS; HIGH-PRESSURE; MIGRATION; NANOPARTICLES; EXPOSURE; NANOSILVER AB This article is one of a series of 4 that report on a task of the NanoRelease Food Additive project of the Intl. Life Science Inst. Center for Risk Science Innovation and Application to identify, evaluate, and develop methods that are needed to confidently detect, characterize, and quantify intentionally produced engineered nanomaterials (ENMs) released from food along the alimentary tract. This particular article focuses on the problem of detecting ENMs that become released into food indirectly from food contact materials. In this review, an in-depth analysis of the release literature is presented and relevant release mechanisms are discussed. The literature review includes discussion of articles related to the release phenomenon in general, as experimental methods to detect ENMs migrating from plastic materials into other (nonfood) complex matrices were determined to be relevant to the focus problem of food safety. From the survey of the literature, several control points were identified where characterization data on ENMs and materials may be most valuable. The article concludes with a summary of findings and a discussion of potential knowledge gaps and targets for method development in this area. C1 [Noonan, Gregory O.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Whelton, Andrew J.] Univ S Alabama, Dept Civil Engn, Mobile, AL 36688 USA. [Carlander, David] Nanotechnol Ind Assoc, B-1050 Brussels, Belgium. [Duncan, Timothy V.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60516 USA. RP Duncan, TV (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60516 USA. EM timothy.duncan@fda.hhs.gov OI Whelton, Andrew/0000-0001-5934-3081 FU Pew Charitable Trusts; US Food and Drug Administration, Health Canada, ILSI North America; Coca-Cola Co.; Illinois Inst. of Technology's Inst. for Food Safety and Health; ILSI Research Foundation; USDA Natl. Research Initiative Agriculture and Food Research Initiative; US Environmental Protection Agency; Natl. Science Foundation FX The authors of this report are grateful to the following individuals for their expert input and support for this effort (alphabetically listed): Maurizio Avella, Joe Hotchkiss, Anil Patri, Ruud Peters, Jonathan Powell, Vicki Stone, Scott Thurmond, Jim Waldman, Stefan Weigel, and Jun Jie Yin. Experts were convened and initial framing concepts were developed for this article by the NRFA Steering Committee (http://www.ilsi.org/ResearchFoundation/RSIA/Pages/FoodAdditiveSteeringC ommittee.aspx and http://www.ilsi.org/ResearchFoundation/RSIA/Pages/NRFA_TaskGroup1.aspx), which operates as an independent public-private partnership. Project management and editing support was provided to the NanoRelease project experts by Richard Canady, Lyubov Tsytsikova, Christina West, Molly Bloom, and Elyse Lee of the ILSI Research Foundation. This phase of the project was funded by the Pew Charitable Trusts, the US Food and Drug Administration, Health Canada, ILSI North America, the Coca-Cola Co., the Illinois Inst. of Technology's Inst. for Food Safety and Health, and the ILSI Research Foundation. Substantial in-kind support was provided by the Nanotechnology Industries Assoc. Furthermore, this material is partly based upon work supported by the USDA Natl. Research Initiative Agriculture and Food Research Initiative, the US Environmental Protection Agency, and the Natl. Science Foundation. NR 61 TC 18 Z9 18 U1 6 U2 68 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1541-4337 J9 COMPR REV FOOD SCI F JI Compr. Rev. Food. Sci. Food Saf. PD JUL PY 2014 VL 13 IS 4 BP 679 EP 692 DI 10.1111/1541-4337.12079 PG 14 WC Food Science & Technology SC Food Science & Technology GA AJ9LH UT WOS:000338031400018 ER PT J AU Singh, G Stephan, C Westerhoff, P Carlander, D Duncan, TV AF Singh, Gurmit Stephan, Chady Westerhoff, Paul Carlander, David Duncan, Timothy V. TI Measurement Methods to Detect, Characterize, and Quantify Engineered Nanomaterials in Foods SO COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY LA English DT Review DE characterization; detection; food safety; measurement methods; nanomaterials; nanotechnology; nanotoxicology; sampling ID CLOUD POINT EXTRACTION; PLASMA-MASS SPECTROMETRY; FIELD-FLOW FRACTIONATION; SCANNING-ELECTRON-MICROSCOPY; SILVER NANOPARTICLES; GOLD NANOPARTICLES; HYDRODYNAMIC CHROMATOGRAPHY; ENVIRONMENTAL WATERS; CONSUMER PRODUCTS; QUANTIFICATION AB This article is one of a series of 4 that reports on a task of the NanoRelease Food Additive project of the International Life Science Institute Center for Risk Science Innovation and Application to identify, evaluate, and develop methods that are needed to confidently detect, characterize, and quantify intentionally produced engineered nanomaterials (ENMs) released from food along the alimentary tract. This particular article focuses on the problem of detecting ENMs in food, paying special attention to matrix interferences and how to deal with them. In this review, an in-depth analysis of the literature related to detection of ENMs in complex matrices is presented. The literature review includes discussions of sampling methods, such as centrifugation and ENM extraction. Available analytical methods, as well as emerging methods, are also presented. The article concludes with a summary of findings and an overview of potential knowledge gaps and targets for method development in this area. C1 [Singh, Gurmit] Hlth Canada, Food Res Div, Bur Chem Safety, Ottawa, ON K1A 0L2, Canada. [Stephan, Chady] PerkinElmer Inc, Woodbridge, ON L4L 8H1, Canada. [Westerhoff, Paul] Arizona State Univ, Sch Sustainable Engn & Built Environm, Tempe, AZ 85287 USA. [Carlander, David] Nanotechnol Ind Assoc, B-1050 Brussels, Belgium. [Duncan, Timothy V.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60516 USA. RP Duncan, TV (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60516 USA. EM timothy.duncan@fda.hhs.gov RI Geracitano, Laura/E-6926-2013 FU Pew Charitable Trusts; US Food and Drug Administration (US FDA), Health Canada, ILSI North America; Coca-Cola Co.; Illinois Inst. of Technology's Inst. for Food Safety and Health; ILSI Research Foundation; USDA Natl. Research Initiative Agriculture and Food Research Initiative; US Environmental Protection Agency; Nat.l Science Foundation FX The authors of this report are grateful to the following individuals for their expert input and support for this effort (alphabetically listed): Maurizio Avella, Joe Hotchkiss, Anil Patri, Ruud Peters, Jonathan Powell, Vicki Stone, Scott Thurmond, Jim Waldman, Stefan Weigel, and Jun Jie Yin. Experts were convened and initial framing concepts were developed for this article by the NRFA Steering Committee (http://www.ilsi.org/ResearchFoundation/RSIA/Pages/FoodAdditiveSteeringC ommittee.aspx and http://www.ilsi.org/ResearchFoundation/RSIA/Pages/NRFA_TaskGroup1.aspx), which operates as an independent public-private partnership. Project management and editing support was provided to the NanoRelease project experts by Richard Canady, Lyubov Tsytsikova, Christina West, Molly Bloom, and Elyse Lee of the ILSI Research Foundation. This phase of the project was funded by the Pew Charitable Trusts, the US Food and Drug Administration (US FDA), Health Canada, ILSI North America, the Coca-Cola Co., the Illinois Inst. of Technology's Inst. for Food Safety and Health, and the ILSI Research Foundation. Substantial in-kind support was provided by the Nanotechnology Industries Assoc. Furthermore, this material is partly based upon work supported by the USDA Natl. Research Initiative Agriculture and Food Research Initiative, the US Environmental Protection Agency, and Nat.l Science Foundation. NR 63 TC 28 Z9 28 U1 4 U2 81 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1541-4337 J9 COMPR REV FOOD SCI F JI Compr. Rev. Food. Sci. Food Saf. PD JUL PY 2014 VL 13 IS 4 BP 693 EP 704 DI 10.1111/1541-4337.12078 PG 12 WC Food Science & Technology SC Food Science & Technology GA AJ9LH UT WOS:000338031400019 ER PT J AU Alger, H Momcilovic, D Carlander, D Duncan, TV AF Alger, Heather Momcilovic, Dragan Carlander, David Duncan, Timothy V. TI Methods to Evaluate Uptake of Engineered Nanomaterials by the Alimentary Tract SO COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY LA English DT Review DE alimentary tract; characterization; detection; food safety; measurement methods; nanotechnology; nanotoxicology ID MESOPOROUS SILICA NANOPARTICLES; COATED GOLD NANOPARTICLES; ZINC-OXIDE NANOPARTICLES; FIELD-FLOW FRACTIONATION; EVERTED GUT SAC; SILVER NANOPARTICLES; IN-VIVO; PARTICLE-SIZE; RAMAN-SPECTROSCOPY; CACO-2 CELLS AB This article is one of a series of 4 that report on a task of the NanoRelease Food Additive project of the International Life Science Institute Center for Risk Science Innovation and Application to identify, evaluate, and develop methods that are needed to confidently detect, characterize, and quantify intentionally produced engineered nanomaterials (ENMs) released from food along the alimentary tract. This particular article focuses on the problem of detecting and characterizing ENMs in the various compartments of the alimentary tract after they have been ingested from dietary sources. An in depth analysis of the literature related to oral toxicity of ENMs is presented, paying particular attention to analytical methodology and sample preparation. The review includes a discussion of model systems that can be used to study oral uptake of ENMs in the absence of human toxicological data or other live-animal studies. The strengths and weaknesses of various analytical and sample preparation techniques are discussed. The article concludes with a summary of findings and a discussion of potential knowledge gaps and targets for method development in this area. RP Duncan, TV (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60516 USA. EM timothy.duncan@fda.hhs.gov RI Geracitano, Laura/E-6926-2013 FU Pew Charitable Trusts; US Food and Drug Administration, Health Canada, ILSI North America; Coca-Cola Co.; Illinois Inst. of Technology's Inst. for Food Safety and Health; ILSI Research Foundation; USDA Natl. Research Initiative Agriculture and Food Research Initiative; US Environmental Protection Agency; Natl. Science Foundation FX The authors of this report are grateful to the following individuals for their expert input and support for this effort (alphabetically listed): Maurizio Avella, Joe Hotchkiss, Anil Patri, Ruud Peters, Jonathan Powell, Vicki Stone, Scott Thurmond, Jim Waldman, Stefan Weigel, and Jun Jie Yin. Experts were convened and initial framing concepts were developed for this article by the NanoRelease Food Additive Steering Committee (http://www.ilsi.org/ResearchFoundation/RSIA/Pages/FoodAdditiveSteeringC ommittee.aspx and http://www.ilsi.org/ResearchFoundation/RSIA/Pages/NRFA_TaskGroup1.aspx), which operates as an independent public-private partnership. Project management and editing support was provided to the NanoRelease project experts by Richard Canady, Lyubov Tsytsikova, Christina West, Molly Bloom, and Elyse Lee of the ILSI Research Foundation. This phase of the project was funded by the Pew Charitable Trusts, the US Food and Drug Administration, Health Canada, ILSI North America, the Coca-Cola Co., the Illinois Inst. of Technology's Inst. for Food Safety and Health, and the ILSI Research Foundation. Substantial in-kind support was provided by the Nanotechnology Industries Assoc. Furthermore, this material is partly based upon work supported by the USDA Natl. Research Initiative Agriculture and Food Research Initiative, the US Environmental Protection Agency, and Natl. Science Foundation. NR 88 TC 11 Z9 11 U1 5 U2 52 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1541-4337 J9 COMPR REV FOOD SCI F JI Compr. Rev. Food. Sci. Food Saf. PD JUL PY 2014 VL 13 IS 4 BP 705 EP 729 DI 10.1111/1541-4337.12077 PG 25 WC Food Science & Technology SC Food Science & Technology GA AJ9LH UT WOS:000338031400020 ER PT J AU Yada, RY Buck, N Canady, R DeMerlis, C Duncan, T Janer, G Juneja, L Lin, MS McClements, DJ Noonan, G Oxley, J Sabliov, C Tsytsikova, L Vazquez-Campos, S Yourick, J Zhong, QX Thurmond, S AF Yada, Rickey Y. Buck, Neil Canady, Richard DeMerlis, Chris Duncan, Timothy Janer, Gemma Juneja, Lekh Lin, Mengshi McClements, David Julian Noonan, Gregory Oxley, James Sabliov, Cristina Tsytsikova, Lyubov Vazquez-Campos, Socorro Yourick, Jeff Zhong, Qixin Thurmond, Scott TI Engineered Nanoscale Food Ingredients: Evaluation of Current Knowledge on Material Characteristics Relevant to Uptake from the Gastrointestinal Tract SO COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY LA English DT Review DE bioavailability; food ingredient; nanotechnology ID IN-WATER EMULSIONS; BETA-CAROTENE BIOACCESSIBILITY; SOLID LIPID NANOPARTICLES; ZINC-OXIDE NANOPARTICLES; CONTROLLED DRUG-DELIVERY; OF-THE-ART; SILVER NANOPARTICLES; PLGA NANOPARTICLES; ZEIN NANOPARTICLES; PARTICLE-SIZE AB The NanoRelease Food Additive project developed a catalog to identify potential engineered nanomaterials (ENMs) used as ingredients, using various food-related databases. To avoid ongoing debate on defining the term nanomaterial, NanoRelease did not use any specific definition other than the ingredient is not naturally part of the food chain, and its dimensions are measured in the nanoscale. Potential nanomaterials were categorized based on physical similarity; analysis indicated that the range of ENMs declared as being in the food chain was limited. Much of the catalog's information was obtained from product labeling, likely resulting in both underreporting (inconsistent or absent requirements for labeling) and/or overreporting (inability to validate entries, or the term nano was used, although no ENM material was present). Three categories of ingredients were identified: emulsions, dispersions, and their water-soluble powdered preparations (including lipid-based structures); solid encapsulates (solid structures containing an active material); and metallic or other inorganic particles. Although much is known regarding the physical/chemical properties for these ingredient categories, it is critical to understand whether these properties undergo changes following their interaction with food matrices during preparation and storage. It is also important to determine whether free ENMs are likely to be present within the gastrointestinal tract and whether uptake of ENMs may occur in their nanoform physical state. A practical decision-making scheme was developed to help manage testing requirements. C1 [Yada, Rickey Y.] Univ Guelph, Guelph, ON N1G 2W1, Canada. [Buck, Neil] ILSI Europe Novel Foods & Nanotechnol Task Force, Brussels, Belgium. [Canady, Richard; Tsytsikova, Lyubov] Res Fdn, Intl Life Sci Inst, Washington, DC USA. [DeMerlis, Chris] Colorcon Inc, West Point, PA USA. [Duncan, Timothy] US FDA, Bedford Pk, IL USA. [Janer, Gemma; Vazquez-Campos, Socorro] Leitat Technol Ctr, Terrassa, Spain. [Juneja, Lekh] Taiyo Kagaku Co, Yokaichi, Mie, Japan. [Lin, Mengshi] Univ Missouri, Columbia, MO USA. [McClements, David Julian] Univ Massachusetts, Amherst, MA 01003 USA. [Noonan, Gregory; Yourick, Jeff; Thurmond, Scott] US FDA, College Pk, MD USA. [Oxley, James] Southwest Res Inst, San Antonio, TX USA. [Sabliov, Cristina] Louisiana State Univ, Baton Rouge, LA 70803 USA. [Zhong, Qixin] Univ Tennessee, Knoxville, TN USA. RP Yada, RY (reprint author), Univ Guelph, Guelph, ON N1G 2W1, Canada. EM ryada@uoguelph.ca FU Pew Charitable Trusts; US Food and Drug Administration, Health Canada, ILSI North America; Coca-Cola Co.; Illinois Inst. of Technology's Inst. for Food Safety and Health; ILSI Research Foundation; Cooperative State Research, Extension, Education Service, US Dept. of Agriculture (USDA); Massachusetts Agricultural Experiment Station; USDA Natl. Research Initiative Agriculture and Food Research Initiative; US Environmental Protection Agency; USDA; Natl. Science Foundation program FX Experts were convened and initial framing concepts were developed for this article by the NanoRelease Food Additive Steering Committee (http://www.ilsi.org/ResearchFoundation/RSIA/Pages/FoodAdditiveSteeringC ommittee.aspx and http://www.ilsi.org/ResearchFoundation/RSIA/Pages/NRFA_TaskGroup1.aspx), which operates as an independent public-private partnership. This phase of the project was funded by the Pew Charitable Trusts, the US Food and Drug Administration, Health Canada, ILSI North America, the Coca-Cola Co., the Illinois Inst. of Technology's Inst. for Food Safety and Health, and the ILSI Research Foundation. Substantial in-kind support was provided by the Nanotechnology Industries Assoc.; This material is partly based upon work supported by the Cooperative State Research, Extension, Education Service, US Dept. of Agriculture (USDA), Massachusetts Agricultural Experiment Station, the USDA Natl. Research Initiative Agriculture and Food Research Initiative, and the US Environmental Protection Agency, USDA, and Natl. Science Foundation program. NR 81 TC 16 Z9 16 U1 8 U2 97 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1541-4337 J9 COMPR REV FOOD SCI F JI Compr. Rev. Food. Sci. Food Saf. PD JUL PY 2014 VL 13 IS 4 BP 730 EP 744 DI 10.1111/1541-4337.12076 PG 15 WC Food Science & Technology SC Food Science & Technology GA AJ9LH UT WOS:000338031400021 ER PT J AU Awotwe-Otoo, D Agarabi, C Khan, MA AF Awotwe-Otoo, David Agarabi, Cyrus Khan, Mansoor A. TI An Integrated Process Analytical Technology (PAT) Approach to Monitoring the Effect of Supercooling on Lyophilization Product and Process Parameters of Model Monoclonal Antibody Formulations SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE lyophilization; process analytical technology (PAT); primary drying; secondary drying; ice nucleation; monoclonal antibody; formulation; freeze drying; product temperature; dry layer thickness ID MANOMETRIC TEMPERATURE-MEASUREMENT; PRIMARY DRYING RATE; NUCLEATION TEMPERATURE; PROTEIN FORMULATIONS; PROCESS PERFORMANCE; QUALITY ATTRIBUTES; ICE NUCLEATION; IN-LINE; SPECTROSCOPY; PHARMACEUTICALS AB The aim of the present study was to apply an integrated process analytical technology (PAT) approach to control and monitor the effect of the degree of supercooling on critical process and product parameters of a lyophilization cycle. Two concentrations of a mAb formulation were used as models for lyophilization. ControLyo technology was applied to control the onset of ice nucleation, whereas tunable diode laser absorption spectroscopy (TDLAS) was utilized as a noninvasive tool for the inline monitoring of the water vapor concentration and vapor flow velocity in the spool during primary drying. The instantaneous measurements were then used to determine the effect of the degree of supercooling on critical process and product parameters. Controlled nucleation resulted in uniform nucleation at lower degrees of supercooling for both formulations, higher sublimation rates, lower mass transfer resistance, lower product temperatures at the sublimation interface, and shorter primary drying times compared with the conventional shelf-ramped freezing. Controlled nucleation also resulted in lyophilized cakes with more elegant and porous structure with no visible collapse or shrinkage, lower specific surface area, and shorter reconstitution times compared with the uncontrolled nucleation. Uncontrolled nucleation however resulted in lyophilized cakes with relatively lower residual moisture contents compared with controlled nucleation. TDLAS proved to be an efficient tool to determine the endpoint of primary drying. There was good agreement between data obtained from TDLAS-based measurements and SMART technology. ControLyo technology and TDLAS showed great potential as PAT tools to achieve enhanced process monitoring and control during lyophilization cycles. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2042-2052, 2014 C1 [Awotwe-Otoo, David; Agarabi, Cyrus; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, OPS,CDER, Rockville, MD 20857 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, OPS,CDER, Rockville, MD 20857 USA. EM Mansoor.Khan@fda.hhs.gov FU Office of Chief Scientist, US FDA FX Financial assistance from the Office of Chief Scientist, US FDA is gratefully acknowledged for medical counter measure (mcm) infrastructure grant. The authors would like to thank Dr. Kurt Brorson of OBP for providing the mAb as a model drug to understand the effect of product and process parameters. NR 36 TC 4 Z9 4 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 EI 1520-6017 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUL PY 2014 VL 103 IS 7 BP 2042 EP 2052 DI 10.1002/jps.24005 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA AJ9IX UT WOS:000338023700014 PM 24840395 ER PT J AU Butler, KS Casey, BJ Garborcauskas, GVM Dair, BJ Elespuru, RK AF Butler, Kimberly S. Casey, Brendan J. Garborcauskas, Garret V. M. Dair, Benita J. Elespuru, Rosalie K. TI Assessment of titanium dioxide nanoparticle effects in bacteria: Association, uptake, mutagenicity, co-mutagenicity and DNA repair inhibition SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Bacterial mutagenesis; Nanoparticle uptake; Flow cytometry; TEM; EDS ID PROTEIN CORONA; DRUG-DELIVERY; GENOTOXICITY; NANOMATERIALS; NANOTECHNOLOGY; GUIDELINES; TOXICITY AB Due to their unique properties, the use of nanoparticles (NPs) is expanding; these same properties may affect their potential risk to humans. However, standard methods for genotoxicity assessment may not be adequate for NPs; altered tests reported here have been developed to address perceived inadequacies. The bacterial reverse mutation assay is an essential part of the battery of tests to determine genotoxicity. The utility of this test for assessing NPs is currently questioned, due to negative results seemingly caused by failure of particle uptake. To probe uptake issues, we examined the physical state in different media, dose and time dependent association, uptake and mutagenicity of titanium dioxide (TiO2) NPs in Salmonella typhimurium and Escherichia coli. The NPs suspended in water were characterized using dynamic light scattering, NP tracking analysis and transmission electron microscopy. NP association with bacteria was assessed by flow cytometry. Association was found to be time and dose dependent, with maximal association by 60 min. Therefore mutagenicity was assessed after a 60 min pre-incubation in a miniaturized assay demonstrating enhanced sensitivity. To assess potential indirect effects on bacterial mutagenicity, the effect of TiO2 NPs on the action of standard mutagens or on DNA repair capability was also investigated. TiO2 NPs did not affect mutant yields in standard strains of S. typhimurium or E. coli, including those detecting oxidative damage, using the modified methods. Nor did TiO2 NPs affect the action of standard mutagens or DNA excision repair capability. Despite particle association with the bacteria, subsequent analysis using electron microscopy and energy dispersive x-ray spectroscopy indicated that the NPs were not internalized. This work demonstrates that additional studies, including flow cytometry, are valuable tools for understanding the action of NPs in biological systems. Published by Elsevier B.V. C1 [Butler, Kimberly S.; Garborcauskas, Garret V. M.; Elespuru, Rosalie K.] US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Biol, Silver Spring, MD 20993 USA. [Casey, Brendan J.; Dair, Benita J.] US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Chem & Mat Sci, Silver Spring, MD 20993 USA. RP Elespuru, RK (reprint author), FDA CDRH OSEL DB, Fed Labs White Oak, Bldg 64-3020,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Rosalie.Elespuru@fda.hhs.gov FU National Cancer Institute Interagency Oncology Taskforce; Office of Science and Engineering Laboratories, CDRH, FDA FX This study was supported by funds provided by the National Cancer Institute Interagency Oncology Taskforce and the Office of Science and Engineering Laboratories, CDRH, FDA. The authors would like to thank MCM Flow Cytometry Facility and Heba Degheidy in the Center for Devices and Radiologic Health, Office of Science and Engineering Laboratories, Division of Biology for training in flow cytometry and use of the facility. NR 27 TC 8 Z9 8 U1 1 U2 37 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 EI 1879-3592 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUL 1 PY 2014 VL 768 BP 14 EP 22 DI 10.1016/j.mrgentox.2014.04.008 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA AJ7NM UT WOS:000337883400003 PM 24769488 ER PT J AU Jin, TC Wang, Y Chen, YW Albillos, SM Kothary, MH Fu, TJ Tankersley, B McHugh, TH Zhang, YZ AF Jin, Tengchuan Wang, Yang Chen, Yu-Wei Albillos, Silvia M. Kothary, Mahendra H. Fu, Tong-Jen Tankersley, Boyce McHugh, Tara H. Zhang, Yu-Zhu TI Isolation and characterization of Korean pine (Pinus koraiensis) convicilin SO PLANT PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE Storage protein; Chemical denaturation; Stability; Potential allergen; Protein folding ID PISUM-SATIVUM-L; SEED STORAGE PROTEIN; MAJOR ALLERGENS; PEA VICILIN; NUTS; PURIFICATION; ANAPHYLAXIS; SUBUNITS AB A vicilin-like globulin seed storage protein, termed convicilin, was isolated for the first time from Korean pine (Pinus koraiensis). SDS-PAGE analysis revealed that Korean pine convicilin was post-translationally processed. The N-terminal peptide sequences of its components were determined. These peptides could be mapped to a protein translated from an embryo abundant transcript isolated in this study. Similar to vicilin, native convicilin appeared to be homotrimeric. Differential scanning calorimetry (DSC) analyses revealed that this protein is less resistant to thermal treatment than Korean pine vicilin. Its transition temperature was 75.57 degrees C compared with 84.13 degrees C for vicilin. The urea induced folding-unfolding equilibrium of pine convicilin monitored by intrinsic fluorescence could be interpreted in terms of a two-state model, with a C-m of 4.41 +/- 0.15 M. Published by Elsevier Masson SAS. C1 [Jin, Tengchuan; Wang, Yang; Chen, Yu-Wei; Zhang, Yu-Zhu] Illinois Inst Technol, Dept Biol & Chem Sci, Chicago, IL 60616 USA. [Albillos, Silvia M.] Illinois Inst Technol, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Fu, Tong-Jen] US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Tankersley, Boyce] Chicago Bot Garden, Chicago, IL 60022 USA. [McHugh, Tara H.; Zhang, Yu-Zhu] USDA ARS, Hlth Proc Foods Res Unit, Western Reg Res Ctr, Albany, CA 94710 USA. RP Zhang, YZ (reprint author), USDA ARS, Hlth Proc Foods Res Unit, Western Reg Res Ctr, 800 Buchanan St, Albany, CA 94710 USA. EM jint@niaid.nih.gov; yuzhu.zhang@ars.usda.gov RI Albillos, Silvia/D-1276-2016; OI Albillos, Silvia/0000-0002-3273-0126; Zhang, Yuzhu/0000-0001-7882-5692; jin, tengchuan/0000-0002-1395-188X NR 25 TC 1 Z9 1 U1 5 U2 16 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0981-9428 J9 PLANT PHYSIOL BIOCH JI Plant Physiol. Biochem. PD JUL PY 2014 VL 80 BP 97 EP 104 DI 10.1016/j.plaphy.2014.03.019 PG 8 WC Plant Sciences SC Plant Sciences GA AJ9CO UT WOS:000338004600012 PM 24735553 ER PT J AU Herman, EH Knapton, A Liu, YM Lipshultz, SE Estis, J Todd, J Woodward, RA Cochran, T Zhang, J Poirier, MC AF Herman, Eugene H. Knapton, Alan Liu, Yongmin Lipshultz, Steven E. Estis, Joel Todd, John Woodward, Ruth A. Cochran, Thomas Zhang, Jun Poirier, Miriam C. TI The Influence of Age on Serum Concentrations of Cardiac Troponin I: Results in Rats, Monkeys, and Commercial Sera SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cardiac troponin I; Sprague-Dawley rats; patas monkeys; young age ID STAGE HEART-FAILURE; MYOCARDIAL-INFARCTION; EXPRESSION; RELEASE; MARKERS; INJURY; VALUES; ASSAY; CARDIOMYOCYTES; IMMUNOASSAYS AB Cardiac troponins serve as serum biomarkers of myocardial injury. The current study examined the influence of age on serum concentrations of cardiac troponin I (cTnI). An ultrasensitive immunoassay was used to monitor cTnI concentrations in Sprague-Dawley (SD) rats and Erythrocebus patas monkeys of different ages. The mean cTnI concentrations were highest in 10-day-old rats compared to 25-, 40-, and 80-day-old SD rats. Cardiomyocyte remodeling was apparent in hearts from 10-day-old SD rats as evident by hypercellularity, irregularly shaped nuclei, and moderate numbers of myocytes undergoing mitosis and apoptosis. The mean concentration of cTnI in 5 newborn monkeys was considerably higher than that of three 1-year-old monkeys. Evidence of cardiomyocyte remodeling was also observed in these newborn hearts (loss of myofibrils and cytoplasmic vacuolation). Commercial animal serum samples were also analyzed. The concentrations of cTnI detected in fetal equine and porcine serum were considerably higher than that found in adult equine and porcine serum samples Likewise, fetal bovine serum had higher cTnI concentrations (>2,400 pg/ml) than did adult caprine and laprine samples (2.5-2.7 pg/ml). The present study found age-related differences in cTnI concentrations, with higher levels occurring at younger ages. This effect was consistent across several animal species. C1 [Herman, Eugene H.; Knapton, Alan; Zhang, Jun] US FDA, Div Drug Safety Res, Silver Spring, MD 20993 USA. [Liu, Yongmin; Poirier, Miriam C.] NCI, NIH, Carcinogen DNA Interact Sect, Bethesda, MD 20892 USA. [Lipshultz, Steven E.; Cochran, Thomas] Univ Miami, Dept Pediat, Leonard M Miller Sch Med, Mailman Ctr Child Dev, Miami, FL 33152 USA. [Estis, Joel; Todd, John] Singulex Inc, Alameda, CA USA. [Woodward, Ruth A.] NIH, Shared Anim Facil, Anim Ctr, Dickerson, MD USA. RP Herman, EH (reprint author), US FDA, Div Drug Safety Res HFD 910, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM eugene.herman@fda.hhs.gov NR 39 TC 2 Z9 2 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL PY 2014 VL 42 IS 5 BP 888 EP 896 DI 10.1177/0192623313505154 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA AJ9GX UT WOS:000338017200011 PM 24129761 ER PT J AU Das, SS Coburn, JC Tack, C Schwerin, MR Richardson, DC AF Das, Srilekha Sarkar Coburn, James C. Tack, Charles Schwerin, Matthew R. Richardson, D. Coleman TI Exposure of natural rubber to personal lubricants - swelling and stress relaxation as potential indicators of reduced seal integrity of non-lubricated male condoms SO CONTRACEPTION LA English DT Article DE Condom; Lubricant; Swelling; Stress relaxation; Natural rubber; Latex; Seal ID VAGINAL INTERCOURSE; LATEX CONDOMS; USE ERRORS; BREAKAGE; SLIPPAGE AB Background: Male condoms act as mechanical barriers to prevent passage of body fluids. For effective use of condoms the mechanical seal is also expected to remain intact under reasonable use conditions, including with personal lubricants. Absorption of low molecular weight lubricant components into the material of male condoms may initiate material changes leading to swelling and stress relaxation of the polymer network chains that could affect performance of the sealing function of the device. Swelling indicates both a rubber-solvent interaction and stress relaxation, the latter of which may indicate and/or result in a reduced seal pressure in the current context. Methods: Swelling and stress relaxation of natural rubber latex condoms were assessed in a laboratory model in the presence of silicone-, glycol-, and water-based lubricants. Results: Within 15 minutes, significant swelling (>= 6 %) and stress reduction >= 12 %) of condoms were observed with 2 out of 4 silicone-based lubricants tested, but neither was observed with glycol- or water-based lubricants tested. Under a given strain, reduction in stress was prominent during the swelling processes, but not after the process was complete. Conclusions: Lubricant induced swelling and stress relaxation may loosen the circumferential stress responsible for the mechanical seal. Swelling and stress relaxation behavior of latex condoms in the presence of personal lubricants may be useful tests to identify lubricant-rooted changes in condom-materials. Implication: For non-lubricated latex condoms, material characteristics - which are relevant to failure - may change in the presence of a few silicone-based personal lubricants. These changes may in turn induce a loss of condom seal during use, specifically at low strain conditions. Published by Elsevier Inc. C1 [Das, Srilekha Sarkar; Coburn, James C.; Schwerin, Matthew R.; Richardson, D. Coleman] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Tack, Charles] Marquette Univ, Milwaukee, WI 53233 USA. RP Das, SS (reprint author), FDA CDRH OSEL, Div Chem & Mat Sci, 10903 New Hampshire Ave,WO-64,Room 3074, Silver Spring, MD 20993 USA. EM srilekha.das@fda.hhs.gov FU US Food and Drug Administration/Center for Devices; Radiological Health/Office of Science and Engineering Laboratories FX Acknowledgement of funding sources- US Food and Drug Administration/Center for Devices and Radiological Health/Office of Science and Engineering Laboratories. NR 28 TC 0 Z9 0 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 EI 1879-0518 J9 CONTRACEPTION JI Contraception PD JUL PY 2014 VL 90 IS 1 BP 86 EP 93 DI 10.1016/j.contraception.2014.01.020 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AJ0HO UT WOS:000337331600015 ER PT J AU Bermingham, EC del Castillo, JRE Radecki, SV AF Bermingham, E. C. del Castillo, J. R. E. Radecki, S. V. TI The use of the noninferiority analysis in clinical studies SO EQUINE VETERINARY JOURNAL LA English DT Editorial Material ID TRIALS C1 [Bermingham, E. C.] US FDA, Ctr Vet Med, Rockville, MD 20857 USA. [del Castillo, J. R. E.] Univ Montreal, Dept Biomed Vet, St Hyacinthe, PQ, Canada. RP Bermingham, EC (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RI del Castillo, Jerome/J-6976-2013 OI del Castillo, Jerome/0000-0001-5046-7926 NR 10 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0425-1644 EI 2042-3306 J9 EQUINE VET J JI Equine Vet. J. PD JUL PY 2014 VL 46 IS 4 BP 399 EP 401 DI 10.1111/evj.12268 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA AJ3RB UT WOS:000337583700002 PM 24909652 ER PT J AU Scully, CG Mitrou, N Braam, B Cupples, WA Chon, KH AF Scully, Christopher G. Mitrou, Nicholas Braam, Branko Cupples, William A. Chon, Ki H. TI Segmentation of Renal Perfusion Signals From Laser Speckle Imaging Into Clusters With Phase Synchronized Dynamics SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Clustering; laser speckle imaging; renal autoregulation; synchronization ID NONNEGATIVE MATRIX FACTORIZATION; PROXIMAL INTRATUBULAR PRESSURE; BLOOD-FLOW DYNAMICS; NITRIC-OXIDE; MYOGENIC AUTOREGULATION; VASCULAR NETWORK; SMOOTH-MUSCLE; OSCILLATIONS; RATS; SENSITIVITY AB Renal perfusion signals contain dynamics arising from the renal autoregulation feedback mechanisms as the contraction and dilation of vessels alter flow patterns. We can capture the time-varying dynamics at points across the renal surface using laser speckle imaging. We segment an imaged area of the renal cortex into clusters with phase synchronized dynamics. Our approach first uses phase coherence with a surrogate data derived threshold to identify synchronized pixel pairs. Non-negative matrix factorization is then applied to segment phase coherence estimates into phase synchronized regions. Themethod is applied to laser speckle imaging of the renal cortex of anaesthetized rats to identify regions on the renal surface with phase synchronized myogenic activity. In three out of six animals imaged after bolus infusion of N-omega-nitro-l-arginine methyl ester (NAM), the renal surfaces are segmented into clusters with high phase coherence. No more than two clusters were identified during control period for any animal. In the remaining three animals, a strong myogenic signal could not be detected in surface perfusion during control or NAM. This method can be used to identify synchronization in renal autoregulation dynamics across the renal surface. C1 [Scully, Christopher G.; Chon, Ki H.] Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA 01609 USA. [Mitrou, Nicholas; Cupples, William A.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada. [Braam, Branko] Univ Alberta, Dept Med, Edmonton, AB T6G 2R3, Canada. [Braam, Branko] Univ Alberta, Dept Physiol, Edmonton, AB T6G 2R3, Canada. RP Scully, CG (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices Radiol Hlth, Silver Spring, MD 20993 USA. EM christopher.scully@fda.hhs.gov; nmitrou@sfu.ca; branko.braam@ualberta.ca; wcupples@sfu.ca; kichon@wpi.edu FU Canadian Institutes of Health Research [MOP-102694]; American Heart Association FX This work was supported by Canadian Institutes of Health Research under Grant MOP-102694. The work of C. G. Scully was supported by an American Heart Association pre-doctoral fellowship. Asterisk indicates corresponding author. NR 34 TC 2 Z9 2 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 EI 1558-2531 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUL PY 2014 VL 61 IS 7 BP 1989 EP 1997 DI 10.1109/TBME.2014.2311118 PG 9 WC Engineering, Biomedical SC Engineering GA AJ6LY UT WOS:000337808200008 PM 24956617 ER PT J AU Sinha, VP Choi, SL Soon, DKW Mace, KF Yeo, KP Lim, STH Howey, DC AF Sinha, Vikram P. Choi, Siak Leng Soon, Danny Kwang Wei Mace, Kenneth F. Yeo, Kwee Poo Lim, Shufen T. H. Howey, Daniel C. TI Single-dose pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 in healthy subjects SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE long-acting basal insulin; pharmacokinetics; glucodynamics ID TO-TARGET TRIAL; NPH INSULIN; ENDOGENOUS INSULIN; GLARGINE; THERAPY; DETEMIR; TYPE-1; MANAGEMENT; SECRETION; EFFICACY AB LY2605541 is a novel basal insulin analog with a prolonged duration of action. Two Phase I studies assessed LY2605541 pharmacokinetics (PK), glucodynamics (GD), and tolerability in healthy subjects. In Study 1, 33 subjects received single subcutaneous (SC) doses of LY2605541 (0.01-2.22U/kg) and insulin glargine (0.5-0.8U/kg) followed by euglycemic clamp for up to 24-36hours. In Study 2, absolute bioavailability of SC LY2605541 was assessed in 8 subjects by comparing dose normalized area under concentration versus time curve of SC against IV administration. Time-to-maximum plasma concentration (medians) and geometric means for half-life (t1/2) and apparent clearance, respectively, ranged from 18.0 to 42.0hours, 24.4-45.5hours, and 1.8-2.8L/h for SC LY2605541, versus 10.0-12.0hours, 12.2-14.9hours, and 51.4-65.2L/h for SC insulin glargine. LY2605541 glucose infusion rate (GIR) profiles were sustained for 36hours versus glargine GIR profiles, which waned at 24hours. After IV administration, LY2605541's geometric mean t1/2 was 2.3hours. LY2605541 intra-subject variability (CV%) was <18% for PK and <32% for GD parameters. The most common adverse events were related to study procedures and were mild-moderate in severity. These results established a well-tolerated baseline dose for LY2605541 with a relatively flat PK profile and low intra-subject variability. C1 [Sinha, Vikram P.; Mace, Kenneth F.; Howey, Daniel C.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Choi, Siak Leng; Soon, Danny Kwang Wei; Yeo, Kwee Poo; Lim, Shufen T. H.] Lilly NUS Ctr Clin Pharmacol, Singapore, Singapore. RP Sinha, VP (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM vikram.sinha@fda.hhs.gov FU Eli Lilly and Company FX This study was funded by Eli Lilly and Company. NR 26 TC 22 Z9 22 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0091-2700 EI 1552-4604 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUL PY 2014 VL 54 IS 7 BP 792 EP 799 DI 10.1002/jcph.276 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ4FH UT WOS:000337627100008 PM 24504686 ER PT J AU Mandl, KD McNabb, M Marks, N Weitzman, ER Kelemen, S Eggleston, EM Quinn, M AF Mandl, Kenneth D. McNabb, Marion Marks, Norman Weitzman, Elissa R. Kelemen, Skyler Eggleston, Emma M. Quinn, Maryanne TI Participatory surveillance of diabetes device safety: a social media-based complement to traditional FDA reporting SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID HEALTH; HYPOGLYCEMIA; IMPROVEMENT; NETWORK AB Background and objective Malfunctions or poor usability Of devices measuring glucose or delivering insulin are reportable to the FDA. Manufacturers submit 99.9% of these reports. We test online social networks as a complementary source to traditional FDA reporting of device-related adverse events. Methods Participatory surveillance of members of a non-profit online social network, TuDiabetes.org, from October 2011 to September 2012. Subjects were volunteers from a group within TuDiabetes, actively engaged online in participatory surveillance. They used the free TuAnalyze app, a privacy-preserving method to report detailed clinical information, available through the network. Network members were polled about finger-stick blood glucose monitors, continuous glucose monitors, and insulin delivery devices, including insulin pumps and insulin pens. Results Of 549 participants, 75 reported device-related adverse events, nearly half (48.0%) requiring intervention from another person to manage the event. Only three (4.0%) of these were reported by participants to the FDA. All TuAnalyze reports contained outcome information compared with 22% of reports to the FDA. Hypoglycemia and hyperglycemia were experienced by 48.0% and 49.3% of participants, respectively. Discussion Members of an online community readily engaged in participatory surveillance. While polling distributed online populations does not yield generalizable, denominator-based rates, this approach can characterize risk within online communities using a bidirectional communication channel that enables reach-back and intervention. Conclusions Engagement of distributed communities in social networks is a viable complementary approach to traditional public health surveillance for adverse events related to medical devices. C1 [Mandl, Kenneth D.; Weitzman, Elissa R.; Kelemen, Skyler] Boston Childrens Hosp, Harvard MIT Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA 02115 USA. [Mandl, Kenneth D.] Boston Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Mandl, Kenneth D.] Harvard Univ, Sch Med, Dept Pediat, Ctr Biomed Informat, Boston, MA 02115 USA. [McNabb, Marion] Boston Univ, Sch Publ Hlth, Dept Int Hlth, Boston, MA USA. [Marks, Norman] US FDA, Silver Spring, MD USA. [Weitzman, Elissa R.] Boston Childrens Hosp, Div Adolescent Med, Boston, MA 02115 USA. [Weitzman, Elissa R.; Quinn, Maryanne] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Eggleston, Emma M.] Harvard Univ, Sch Med, Harvard Pilgrim HealthCare Inst, Dept Populat Med, Boston, MA USA. [Eggleston, Emma M.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Quinn, Maryanne] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Mandl, KD (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM Kenneth_Mandl@Harvard.edu FU Centers for Disease Control and Prevention (CDC) [PO1HK000088]; National Library of Medicine (NIH) grants from the National Center for Advancing Translational Sciences (NIH) [5R01LM007677, G08LM009778, 1U54RR025224] FX This work was supported by PO1HK000088 from the Centers for Disease Control and Prevention (CDC), National Library of Medicine (NIH) grants 5R01LM007677 and G08LM009778, and 1U54RR025224 from the National Center for Advancing Translational Sciences (NIH). NR 26 TC 3 Z9 3 U1 3 U2 16 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2014 VL 21 IS 4 SI SI BP 687 EP 691 DI 10.1136/amiajnl-2013-002127 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA AJ4QJ UT WOS:000337660600022 PM 24355131 ER PT J AU Rajan, S Herbertson, L Bernardo, M Choyke, P AF Rajan, Sunder Herbertson, Luke Bernardo, Marcelino Choyke, Peter TI A Dialyzer-Based Flow System for Validating Dynamic Contrast Enhanced MR Image Acquisition SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE flow-phantom; DCE-MRI; dialyzer; polysulfone ID PHANTOM AB Purpose: Dynamic contrast enhanced magnetic resonance imaging (MRI) has proven to be quite sensitive for the characterization of masses and early response to therapy. However, it is fraught with a number of procedural challenges as well as a lack of standardization. In this article, we describe the use of a simple dialyzer-based flow system to evaluate reproducibility of dynamic contrast enhanced MRI under active flow conditions. Methods: The MR signal during a bolus injection of Gd-DTPA was analyzed to test the precision and variability of contrast agent kinetics during a typical dynamic contrast enhanced MRI sequence. A simple model allows an estimation of the washout rate constant of Gd-DTPA through the polysulfone tubules of the dialyzer. Results: The simple flow phantom described here provided reproducible measurements of the washout rate constants. The washout rate increased from 0.20 +/- 0.005 min(-1) to 0.25 +/- 0.008 min(-1) over 32 weeks. Measurements were also made at week 24 using dynamic computed tomography and found to be 0.27 +/- 0.006 min(-1). Overall, the computed tomography derived rate constants results were found be similar to 12% higher than the corresponding MRI values. Conclusion: In this study, we show that a simple dialyzer-based flow phantom can be used for testing dynamic contrast enhanced MRI pulse sequences and also allows for short-term reproducibility testing of rate constants. (C) 2013 Wiley Periodicals, Inc. C1 [Rajan, Sunder; Herbertson, Luke] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Bernardo, Marcelino] SAIC Frederick, Frederick, MD USA. [Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Rajan, S (reprint author), 10903 New Hampshire Ave,WO 62,Room 1113, Silver Spring, MD 20993 USA. EM sunder.rajan@fda.hhs.gov NR 11 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUL PY 2014 VL 72 IS 1 BP 41 EP 48 DI 10.1002/mrm.24887 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AJ4EK UT WOS:000337624400007 PM 23907806 ER PT J AU Allard, S Enurah, A Strain, E Millner, P Rideout, SL Brown, EW Zheng, J AF Allard, Sarah Enurah, Alexander Strain, Errol Millner, Patricia Rideout, Steven L. Brown, Eric W. Zheng, Jie TI In Situ Evaluation of Paenibacillus alvei in Reducing Carriage of Salmonella enterica Serovar Newport on Whole Tomato Plants SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID BIOCONTROL AGENTS; UNITED-STATES; INACTIVATION; BACTERIA; GROWTH; BACTERIOPHAGES; COLONIZATION; ENTEROBACTER; COMPONENTS; OUTBREAKS AB Recently, tomatoes have been implicated as a primary vehicle in food-borne outbreaks of Salmonella enterica serovar Newport and other Salmonella serovars. Long-term intervention measures to reduce Salmonella prevalence on tomatoes remain elusive for growing and postharvest environments. A naturally occurring bacterium identified by 16S rRNA gene sequencing as Paenibacillus alvei was isolated epiphytically from plants native to the Virginia Eastern Shore tomato-growing region. After initial antimicrobial activity screening against Salmonella and 10 other bacterial pathogens associated with the human food supply, strain TS-15 was further used to challenge an attenuated strain of S. Newport on inoculated fruits, leaves, and blossoms of tomato plants in an insect-screened high tunnel with a split-plot design. Survival of Salmonella after inoculation was measured for groups with and those without the antagonist at days 0, 1, 2, and 3 and either day 5 for blossoms or day 6 for fruits and leaves. Strain TS-15 exhibited broad-range antimicrobial activity against both major food-borne pathogens and major bacterial phytopathogens of tomato. After P. alvei strain TS-15 was applied onto the fruits, leaves, and blossoms of tomato plants, the concentration of S. Newport declined significantly (P <= 0.05) compared with controls. Astonishingly,>90% of the plants had no detectable levels of Salmonella by day 5 for blossoms. The naturally occurring antagonist strain TS-15 is highly effective in reducing the carriage of Salmonella Newport on whole tomato plants. The application of P. alvei strain TS-15 is a promising approach for reducing the risk of Salmonella contamination during tomato production. C1 [Allard, Sarah; Enurah, Alexander; Strain, Errol; Brown, Eric W.; Zheng, Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Allard, Sarah] Univ Maryland, Dept Plant Sci & Landscape Architecture, College Pk, MD 20742 USA. [Millner, Patricia] USDA ARS, Environm Microbial & Food Safety Lab, Beltsville, MD USA. [Rideout, Steven L.] Virginia Tech, Eastern Shore Agr Res & Extens Ctr, Painter, VA USA. RP Zheng, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM jie.zheng@fda.hhs.gov NR 43 TC 8 Z9 8 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2014 VL 80 IS 13 BP 3842 EP 3849 DI 10.1128/AEM.00835-14 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA AI9GR UT WOS:000337241400008 PM 24747888 ER PT J AU Ahn, Y Kim, JM Ahn, H Lee, YJ LiPuma, JJ Hussong, D Cerniglia, CE AF Ahn, Youngbeom Kim, Jeong Myeong Ahn, Hyeri Lee, Yong-Jin LiPuma, John J. Hussong, David Cerniglia, Carl E. TI Evaluation of liquid and solid culture media for the recovery and enrichment of Burkholderia cenocepacia from distilled water SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE Culture media; Recovery; Enrichment; Burkholderia cenocepacia; Distilled water ID CEPACIA COMPLEX; PSEUDOMONAS-CEPACIA; CYSTIC-FIBROSIS; SELECTIVE MEDIA; PSEUDOMALLEI; SURVIVAL; BACTERIA; GROWTH; SOIL; ENUMERATION AB Burkholderia cepacia complex (BCC) presence has been the cause of recalls of both sterile and non-sterile pharmaceutical products since these opportunistic pathogens have been implicated to cause infections to susceptible individuals. BCC are ubiquitous in nature, but in pharmaceutical settings the most common source is contaminated water systems. Some strains of BCC, previously described as Pseudomonas cepacia, were not readily detected by standard culture methods. We have explored different strategies to recover and enrich Burkholderia cenocepacia previously cultured in distilled water for 40 days. Enrichment media of varied nutrient concentrations and composition were used, including modified Tryptic Soy Agar or Broth (TSA or TSB), Reasoner's 2nd Agar or Broth (R2A or R2AB), Brain-Heart Infusion Broth (BHIB), Mueller-Hinton Broth (MHB), and Ashdown's (ASH) medium. Of the various broth media tested, cell growth was significantly greater in TSB and R2AB than in BHIB, MHB, or ASH broth. TSB and R2AB were also compared for their recovery efficiency. Generally, there was no significant difference between the numbers of B. cenocepacia grown on 15 differently modified TSA and five modified R2A solid media. Overall, however, diluted TSA and TSB media, and R2A and R2AB showed better recovery efficiency than TSA and TSB for inocula containing small numbers of cells. All strains persisted in distilled water for 40 days. Broth media were more effective than solid media for recovery of B. cenocepacia from distilled water. These results may assist in improving detection assays with recovery and enrichment strategies to maximize recovery of these fastidious organisms. C1 [Ahn, Youngbeom; Kim, Jeong Myeong; Ahn, Hyeri; Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Ahn, Hyeri] Rutgers State Univ, Dept Biol, New Brunswick, NJ 08903 USA. [Lee, Yong-Jin] Albany State Univ, Dept Nat Sci, Albany, GA 31705 USA. [LiPuma, John J.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. [Hussong, David] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Beltsville, MD USA. RP Ahn, Y (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM young.ahn@fda.hhs.gov FU US Department of Energy FX We thank Drs. John Sutherland and Sangeeta Khare for reviewing the manuscript. This work was supported in part by an interagency agreement between the US Department of Energy and the US Food and Drug Administration to the summer student research program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 33 TC 3 Z9 3 U1 2 U2 10 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1367-5435 EI 1476-5535 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD JUL PY 2014 VL 41 IS 7 BP 1109 EP 1118 DI 10.1007/s10295-014-1442-3 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AI8GZ UT WOS:000337150200007 PM 24756630 ER PT J AU Kun, KE Rose, DA Morris, T Salter, M Lamia, T Bhalakia, A McLees, AW AF Kun, Karen E. Rose, Dale A. Morris, Thomas Salter, Monique Lamia, Tamara Bhalakia, Amee McLees, Anita W. TI Conceptualizing and Measuring Community Preparedness Within Public Health Preparedness and Response: Complexities and Lessons Learned SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Article DE community preparedness; community resilience; performance measurement; public health preparedness AB Since 2001, the Centers for Disease Control and Prevention's Public Health Emergency Preparedness cooperative agreement has supported state, territorial, and local public health departments in preparing for and responding to public health emergencies. This conceptual article describes complexities identified and lessons learned in developing community preparedness performance measures for the Centers for Disease Control and Prevention's public health preparedness program. Challenges arose in (a) defining community; (b) measuring meaningful community engagement; and (c) determining a strategy for collecting, aggregating, and analyzing data from diverse state, territorial, and local health departments. This article contributes to prior work describing conceptual challenges in developing standardized measures of performance at the federal level and suggests ways to potentially mitigate general performance measurement challenges as well as measurement complexities specific to community preparedness. It may be informative for those state, territorial, and local health departments currently implementing (or contemplating implementing) community preparedness activities and for individuals more generally engaged in performance measurement. C1 [Kun, Karen E.] Ctr Dis Control & Prevent, US Dept HHS, Ctr Global Hlth, Atlanta, GA 30333 USA. [Rose, Dale A.; Morris, Thomas] Ctr Dis Control & Prevent, US Dept HHS, Off Publ Hlth Preparedness & Response, Atlanta, GA 30333 USA. [McLees, Anita W.] Ctr Dis Control & Prevent, US Dept HHS, Off State Tribal Local & Territorial Support, Atlanta, GA 30333 USA. [Salter, Monique] US FDA, US Dept HHS, College Pk, MD USA. [Lamia, Tamara; Bhalakia, Amee] ICF Int, Atlanta, GA USA. RP Rose, DA (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Preparedness & Response, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM ido8@cdc.gov NR 16 TC 0 Z9 0 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 EI 1550-5022 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD JUL-AUG PY 2014 VL 20 IS 4 BP E1 EP E5 DI 10.1097/PHH.0b013e3182a5bbcc PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI8DV UT WOS:000337137700001 PM 24322842 ER PT J AU Shah, KB Patel, PG Khairuzzaman, A Bellantone, RA AF Shah, Kosha B. Patel, Piyush G. Khairuzzaman, Akm Bellantone, Robert A. TI An improved method for the characterization of supersaturation and precipitation of poorly soluble drugs using pulsatile microdialysis (PMD) SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Supersaturation; Precipitation; Poorly soluble; Pulsatile microdialysis; PMD; Dissolution ID DELIVERY SYSTEMS; IN-VITRO; ABSORPTION; BIOAVAILABILITY; PERMEABILITY; NUCLEATION; SOLUBILITY; KINETICS AB In current pharmaceutical drug discovery, most candidates are poorly soluble in water, which can result in poor bioavailability. To overcome this problem, formulations that create supersaturation of the drug are a well-studied alternative. Characterizing the dissolution from these systems is challenging because conventional methods, such as sampling with a syringe then filtering with a 0.2-0.45 mu m filter before an HPLC assay, can overestimate the concentration of dissolved drug by allowing nuclei or small precipitated particles to pass, which then dissolve in the HPLC mobile phase. Nuclei and small particles can also cause overestimation of the dissolved concentration when using optical methods. Such overestimations can lead to failure of in vivo prediction of drug bioavailability from supersaturated systems. This paper reports a novel method to determine the free dissolved drug concentration in a dissolution medium using pulsatile microdialysis (PMD). Ibuprofen was used as a model drug for determining precipitation and supersaturation. Supersaturation was induced chemically by changing pH, and also by dissolution/release from an in-house formulation. The adaptation of a previously developed PMD model is summarized, and experimental results comparing dissolved concentrations determined using PMD and direct sampling by syringe and filtering are presented. (C) 2014 Elsevier B.V. All rights reserved. C1 [Shah, Kosha B.; Patel, Piyush G.; Bellantone, Robert A.] Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Div Pharmaceut Sci, Brooklyn, NY 11201 USA. [Khairuzzaman, Akm] US FDA, Silver Spring, MD 20993 USA. [Bellantone, Robert A.] Phys Pharmaceut LLC, Tuckahoe, NY 10707 USA. RP Bellantone, RA (reprint author), Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Div Pharmaceut Sci, 75 Dekalb Ave, Brooklyn, NY 11201 USA. EM rbellant@liu.edu OI Bellantone, Robert/0000-0001-6750-2847 NR 27 TC 10 Z9 10 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 EI 1873-3476 J9 INT J PHARMACEUT JI Int. J. Pharm. PD JUL 1 PY 2014 VL 468 IS 1-2 BP 64 EP 74 DI 10.1016/j.ijpharm.2014.04.012 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH9TT UT WOS:000336486600007 PM 24709210 ER PT J AU Guariento, AH Furtado, KS de Conti, A Campos, A Purgatto, E Carrilho, J Shinohara, EMG Tryndyak, V Han, T Fuscoe, JC Ross, SA Beland, FA Pogribny, IP Moreno, FS AF Guariento, Aline H. Furtado, Kelly S. de Conti, Aline Campos, Adriana Purgatto, Eduardo Carrilho, Jessica Guerra Shinohara, Elvira Maria Tryndyak, Volodymyr Han, Tao Fuscoe, James C. Ross, Sharon A. Beland, Frederick A. Pogribny, Igor P. Moreno, Fernando S. TI Transcriptomic responses provide a new mechanistic basis for the chemopreventive effects of folic acid and tributyrin in rat liver carcinogenesis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE angiogenesis; folic acid; tributyrin; hepatocarcinogenesis; chemoprevention ID ENDOTHELIAL GROWTH-FACTOR; HEPATOCELLULAR-CARCINOMA; CANCER PREVENTION; HEPATOCARCINOGENESIS; ANGIOGENESIS; EXPRESSION; CELLS; INHIBITORS; NEOPLASIA; PROMOTION AB The steady increase in the incidence and mortality of hepatocellular carcinoma (HCC) signifies a crucial need to understand better its pathogenesis to improve clinical management and prevention of the disease. The aim of this study was to investigate molecular mechanisms for the chemopreventive effects of folic acid and tributyrin alone or in combination on rat hepatocarcinogenesis. Male Wistar rats were subjected to a classic "resistant hepatocyte" model of liver carcinogenesis and treated with folic acid and tributyrin alone or in combination for 5 weeks during promotion stage. Treatment with folic acid and tributyrin alone or in combination strongly inhibited the development of glutathione-S-transferase placental form (GSTP)-positive foci. Microarray analysis showed significant changes in gene expression. A total of 498, 655 and 940 of differentially expressed genes, involved in cell cycle, p53-signaling, angiogenesis and Wnt pathways, was identified in the livers of rats treated with folic acid, tributyrin or folic acid and tributyrin. A detailed analysis of these differentially expressed genes revealed that treatments inhibited angiogenesis in the preneoplastic livers. This was evidenced by the fact that 30 out of 77 differentially expressed genes common to all three treatments are involved in the regulation of the angiogenesis pathway. The inhibition of angiogenesis was confirmed by reduced levels of CD34 protein. In conclusion, the tumor-suppressing activity of folic acid and tributyrin is associated with inhibition of angiogenesis at early stages of rat liver carcinogenesis. Importantly, the combination of folic acid and tributyrin has stronger chemopreventive effect than each of the compounds alone. C1 [Guariento, Aline H.; Furtado, Kelly S.; Campos, Adriana; Moreno, Fernando S.] Univ Sao Paulo, Lab Diet Nutr & Canc, Dept Food & Expt Nutr, Sao Paulo, Brazil. [de Conti, Aline; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Purgatto, Eduardo] Univ Sao Paulo, Lab Food Chem & Biochem, Dept Food & Expt Nutr, Sao Paulo, Brazil. [Carrilho, Jessica; Guerra Shinohara, Elvira Maria] Univ Sao Paulo, Fac Pharmaceut Sci, Hematol Lab, Dept Clin & Toxicol Anal, Sao Paulo, Brazil. [Han, Tao; Fuscoe, James C.] Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Moreno, FS (reprint author), Univ Sao Paulo, Lab Diet Nutr & Canc, Sao Paulo, Brazil. EM igor.pogribny@fda.hhs.gov; rmoreno@usp.br RI Purgatto, Eduardo/C-7707-2009; Guerra-Shinohara, Elvira/E-5610-2012; Moreno, Fernando/I-1943-2013 OI Purgatto, Eduardo/0000-0002-7372-1197; Guerra-Shinohara, Elvira/0000-0001-6681-2210; FU Intramural NIH HHS [Z99 CA999999] NR 46 TC 3 Z9 4 U1 1 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2014 VL 135 IS 1 BP 7 EP 18 DI 10.1002/ijc.28642 PG 12 WC Oncology SC Oncology GA AE9TR UT WOS:000334353500002 PM 24302446 ER PT J AU Selvapandiyan, A Dey, R Gannavaram, S Solanki, S Salotra, P Nakhasi, HL AF Selvapandiyan, Angamuthu Dey, Ranadhir Gannavaram, Sreenivas Solanki, Sumit Salotra, Poonam Nakhasi, Hira L. TI Generation of growth arrested Leishmania amastigotes: A tool to develop live attenuated vaccine candidates against visceral leishmaniasis SO VACCINE LA English DT Review DE Leishmania; Centrin; Gene knockout; Amastigote; Cell division; Visceral leishmaniasis; Vaccine ID PROTEINASE-DEFICIENT MUTANTS; CELL-CYCLE; CUTANEOUS LEISHMANIASIS; STABLE TRANSFECTION; PROTECTIVE IMMUNITY; SALIVARY PROTEIN; GENE REPLACEMENT; DELIVERY VEHICLE; HUMAN-DISEASE; TH1 RESPONSE AB Visceral leishmaniasis (VL) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. VL is caused by the protozoan parasite Leishmania donovani or Leishmania infantum. Although several second generation vaccines have been licensed to protect dogs against VL, there are no effective vaccines against human VL [1]. Since people cured of leishmaniasis develop lifelong protection, development of live attenuated Leishmania parasites as vaccines, which can have controlled infection, may be a close surrogate to leishmanization. This can be achieved by deletion of genes involved in the regulation of growth and/or virulence of the parasite. Such mutant parasites generally do not revert to virulence in animal models even under conditions of induced immune suppression due to complete deletion of the essential gene(s). In the Leishmania life cycle, the intracellular amastigote form is the virulent form and causes disease in the mammalian hosts. We developed centrin gene deleted L. donovani parasites that displayed attenuated growth only in the amastigote stage and were found safe and efficacious against virulent challenge in the experimental animal models. Thus, targeting genes differentially expressed in the amastigote stage would potentially attenuate only the amastigote stage and hence controlled infectivity may be effective in developing immunity. This review lays out the strategies for attenuation of the growth of the amastigote form of Leishmania for use as live vaccine against leishmaniasis, with a focus on visceral leishmaniasis. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Selvapandiyan, Angamuthu; Solanki, Sumit] Inst Mol Med, New Delhi, India. [Dey, Ranadhir; Gannavaram, Sreenivas; Nakhasi, Hira L.] FDA, CBER, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. [Solanki, Sumit] CG Bhakta Inst Biotechnol, Tarsadi, Gujarat, India. [Salotra, Poonam] Natl Inst Pathol ICMR, New Delhi, India. RP Selvapandiyan, A (reprint author), Inst Mol Med, New Delhi, India. EM selvapandiyan@immindia.org FU Department of Biotechnology, India [BT/PR12883/AGR/36/618/2009, BT/PR441/MED/15/71/2011] FX Partly supported by funding from the Department of Biotechnology, India No. BT/PR12883/AGR/36/618/2009; BT/PR441/MED/15/71/2011 NR 96 TC 5 Z9 5 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD JUN 30 PY 2014 VL 32 IS 31 BP 3895 EP 3901 DI 10.1016/j.vaccine.2014.05.009 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AK4LO UT WOS:000338396400004 PM 24837513 ER PT J AU Huang, L Zalkikar, J Tiwari, R AF Huang, Lan Zalkikar, Jyoti Tiwari, Ram TI Likelihood ratio based tests for longitudinal drug safety data SO STATISTICS IN MEDICINE LA English DT Article DE safety surveillance; drug exposure; active surveillance; sequential method; longitudinal method ID SIGNAL-DETECTION; CLINICAL-TRIALS; HIP FRACTURE; SURVEILLANCE; GENERATION; RISK AB This article presents longitudinal likelihood ratio test (LongLRT) methods for large databases with exposure information. These methods are applied to a pooled large longitudinal clinical trial dataset for drugs treating osteoporosis with concomitant use of proton pump inhibitors (PPIs). When the interest is in the evaluation of a signal of an adverse event for a particular drug compared with placebo or a comparator, the special case of the LongLRT, referred to as sequential LRT (SeqLRT), is also presented. The results show that there is some possible evidence of concomitant use of PPIs leading to more adverse events associated with osteoporosis. The performance of the proposed LongLRT and SeqLRT methods is evaluated using simulated datasets and shown to be good in terms of (conditional) power and control of type I error over time. The proposed methods can also be applied to large observational databases with exposure information under the US Food and Drug Administration Sentinel Initiative for active surveillance. Published 2014. This article is a US Government work and is in the public domain in the USA. C1 [Huang, Lan; Zalkikar, Jyoti; Tiwari, Ram] US FDA, Div Biometr 5, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. RP Huang, L (reprint author), US FDA, Div Biometr 5, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. EM lan.huang@fda.hhs.gov NR 20 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD JUN 30 PY 2014 VL 33 IS 14 BP 2408 EP 2424 DI 10.1002/sim.6103 PG 17 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA AJ2RY UT WOS:000337509700005 PM 24919793 ER PT J AU Agaku, IT King, BA Husten, CG Bunnell, R Ambrose, BK Hu, SS Holder-Hayes, E Day, HR AF Agaku, Israel T. King, Brian A. Husten, Corinne G. Bunnell, Rebecca Ambrose, Bridget K. Hu, S. Sean Holder-Hayes, Enver Day, Hannah R. TI Tobacco Product Use Among Adults - United States, 2012-2013 SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article ID CIGARETTE-SMOKING C1 [Agaku, Israel T.; King, Brian A.; Bunnell, Rebecca; Hu, S. Sean] CDC, Off Smoking & Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Agaku, Israel T.] CDC, Atlanta, GA 30333 USA. [Husten, Corinne G.; Ambrose, Bridget K.; Holder-Hayes, Enver; Day, Hannah R.] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. RP King, BA (reprint author), CDC, Off Smoking & Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. EM baking@cdc.gov NR 10 TC 105 Z9 105 U1 1 U2 5 PU CENTER DISEASE CONTROL & PREVENTION PI ATLANTA PA MAILSTOP E-90, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD JUN 27 PY 2014 VL 63 IS 25 BP 542 EP 547 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AK8XF UT WOS:000338711300003 PM 24964880 ER PT J AU Fiedler, KL McGrath, SC Callahan, JH Ross, MM AF Fiedler, Katherine L. McGrath, Sara C. Callahan, John H. Ross, Mark M. TI Characterization of Grain-Specific Peptide Markers for the Detection of Gluten by Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE wheat; gliadin; proteomics; LC-MS/MS; celiac disease; gluten-free ID WHEAT GLUTEN; LIQUID-CHROMATOGRAPHY; TARGETED PROTEOMICS; CELIAC-DISEASE; PROTEINS; ASSAY; INTOLERANCE; ACCURACY; CLEAVAGE; BARLEY AB Global and targeted mass spectrometry-based proteomic approaches were developed to discover, evaluate, and apply gluten peptide markers to detect low parts per million (ppm) wheat contamination of oats. Prolamins were extracted from wheat, barley, rye, and oat flours and then reduced, alkylated, and digested with chymotrypsin. The resulting peptides were subjected to LC-MS/MS analysis and database matching. No peptide markers common to wheat, barley, and rye were identified that could be used for global gluten detection. However, many grain-specific peptide markers were identified, and a set of these markers was selected for gluten detection and grain differentiation. Wheat flour was spiked into gluten-free oat flour at concentrations of 1-100,000 ppm and analyzed to determine the lowest concentration at which the wheat "contaminant" could be confidently detected in the mixture. The same 2D ion trap instrument that was used for the global proteomics approach was used for the targeted proteomics approach, providing a seamless transition from target discovery to application. A powerful, targeted MS/MS method enabled detection of two wheat peptide markers at the 10 ppm wheat flour-in-oat flour concentration. Because gluten comprises approximately 10% of wheat flour protein, the reported wheat gluten-specific peptides can enable detection of approximately 1 ppm of wheat gluten in oats. C1 [Fiedler, Katherine L.; McGrath, Sara C.; Callahan, John H.; Ross, Mark M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ross, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM markm.ross@fda.hhs.gov OI McGrath, Sara/0000-0003-4773-4784 NR 39 TC 17 Z9 17 U1 7 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 25 PY 2014 VL 62 IS 25 SI SI BP 5835 EP 5844 DI 10.1021/jf500997j PG 10 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA AK1OH UT WOS:000338183900016 PM 24866027 ER PT J AU Du Le, VN Wang, QZ Gould, T Ramella-Roman, JC Pfefer, TJ AF Du Le, V. N. Wang, Quanzeng Gould, Taylor Ramella-Roman, Jessica C. Pfefer, T. Joshua TI Vascular contrast in narrow-band and white light imaging SO APPLIED OPTICS LA English DT Article ID BARRETTS-ESOPHAGUS; CONVENTIONAL COLONOSCOPY; OPTICAL-PROPERTIES; ENDOSCOPY; DIAGNOSIS; CANCER; TISSUE; SYSTEM; ADENOCARCINOMA; CHROMOENDOSCOPY AB Narrow-band imaging (NBI) is a spectrally selective reflectance imaging technique that is used clinically for enhancing visualization of superficial vasculature and has shown promise for applications such as early endoscopic detection of gastrointestinal neoplasia. We have studied the effect of vessel geometry and illumination wavelength on vascular contrast using idealized geometries in order to more quantitatively understand NBI and broadband or white light imaging of mucosal tissue. Simulations were performed using a three-dimensional, voxel-based Monte Carlo model incorporating discrete vessels. In all cases, either 415 or 540 nm illumination produced higher contrast than white light, yet white light did not always produce the lowest contrast. White light produced the lowest contrast for small vessels and intermediate contrast for large vessels (diameter >= 100 mu m) at deep regions (vessel depth >= 200 mu m). The results show that 415 nm illuminations provided superior contrast for smaller vessels at shallow depths while 540 nm provided superior contrast for larger vessels in deep regions. Besides 540 nm, our studies also indicate the potential of other wavelengths to achieve high contrast of large vessels at deep regions. Simulation results indicate the importance of three key mechanisms in determining spectral variations in contrast: intravascular hemoglobin (Hb) absorption in the vessel of interest, diffuse Hb absorption from collateral vasculature, and bulk tissue scattering. Measurements of NBI contrast in turbid phantoms incorporating 0.1-mm-diameter hemoglobin-filled capillary tubes indicated good agreement with modeling results. These results provide quantitative insights into light-tissue interactions and the effect of device and tissue properties on NBI performance. (C) 2014 Optical Society of America C1 [Du Le, V. N.; Wang, Quanzeng; Gould, Taylor; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Du Le, V. N.; Ramella-Roman, Jessica C.] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM joshua.pfefer@fda.hhs.gov RI Le, Vinh Nguyen Du/E-3859-2015 OI Le, Vinh Nguyen Du/0000-0002-4054-4200 NR 38 TC 3 Z9 3 U1 0 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUN 20 PY 2014 VL 53 IS 18 BP 4061 EP 4071 DI 10.1364/AO.53.004061 PG 11 WC Optics SC Optics GA AK5CV UT WOS:000338442800031 PM 24979441 ER PT J AU Kasar, S Underbayev, C Yuan, Y Hanlon, M Aly, S Khan, H Chang, V Batish, M Gavrilova, T Badiane, F Degheidy, H Marti, G Raveche, E AF Kasar, S. Underbayev, C. Yuan, Y. Hanlon, M. Aly, S. Khan, H. Chang, V. Batish, M. Gavrilova, T. Badiane, F. Degheidy, H. Marti, G. Raveche, E. TI Therapeutic implications of activation of the host gene (Dleu2) promoter for miR-15a/16-1 in chronic lymphocytic leukemia SO ONCOGENE LA English DT Article DE miR-15a/16-1; BSAP; HDAC inhibitor; CLL; NZB ID MALIGNANT B-1 CELLS; HISTONE DEACETYLASE INHIBITOR; ZEALAND BLACK MOUSE; B-CELLS; TRANSCRIPTION FACTOR; MULTIPLE-MYELOMA; MANTLE CELL; IN-SITU; CANCER; PAX5 AB Genetic lesions and other regulatory events lead to silencing of the 13q14 locus in a majority of chronic lymphocytic leukemia (CLL) patients. This locus encodes a pair of critical proapoptotic microRNAs, miR-15a/16-1. Decreased levels of miR-15a/16-1 are critical for the increased survival exhibited by CLL cells. Similarly, in a de novo murine model of CLL, the NZB strain, germline-encoded regulation of the syntenic region resulted in decreased miR-15a/16-1. In this paper, we have identified additional molecular mechanisms regulating miR-15a/16-1 levels and have shown that the transcription factor BSAP (B-cell-specific activator protein) directly interacts with Dleu2, the host gene containing the miR-15a/16-1 loci, and by negative regulation of the Dleu2 promoter, results in repression of miR-15a/16-1 expression. CLL patient B-cell expression levels of BSAP were increased compared with control sources of B cells. With the use of small interfering RNA-mediated repression, the levels of BSAP were decreased in vitro in the NZB-derived malignant B-1 cell line, LNC, and in ex vivo CLL patient peripheral blood mononuclear cells (PBMCs). BSAP knockdown led to an increase in the expression of miR-15a/16-1 and an increase in apoptosis, and a cell cycle arrest in both the cell line and patient PBMCs. Moreover, using Dleu2 promoter analysis by chromatin immunoprecipitation assay, we have shown that BSAP directly interacts with the Dleu2 promoter. Derepression of the Dleu2 promoter via inhibition of histone deacetylation combined with BSAP knockdown increased miR-15a/16-1 expression, and also increased malignant B-cell death. In summary, therapy targeting enhanced host gene Dleu2 transcription may augment CLL therapy. C1 [Kasar, S.; Underbayev, C.; Hanlon, M.; Aly, S.; Khan, H.; Chang, V.; Batish, M.; Gavrilova, T.; Badiane, F.; Raveche, E.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Yuan, Y.] NIH, Bethesda, MD 20892 USA. [Chang, V.] Vet Affairs New Jersey Hlth Care Syst, E Orange, NJ USA. [Degheidy, H.; Marti, G.] OSEL CDRH FDA, White Oak, MD USA. RP Raveche, E (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol, 185S Orange Ave,MSB C-512, Newark, NJ 07103 USA. EM batishmo@njms.rutgers.edu; raveches@njms.rutgers.edu FU NSF/FDA/SIR [1238375]; NIH [R01CA12926]; Early Independence Award [1DP5OD012160-01]; UMDNJ-NJMS Flow Cytometry Core FX This work was supported by NSF/FDA/SIR No. 1238375 and NIH R01CA12926 (ESR). Early Independence Award # 1DP5OD012160-01 (MB). We thank the UMDNJ-NJMS Flow Cytometry Core for their support. NR 66 TC 5 Z9 6 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUN 19 PY 2014 VL 33 IS 25 BP 3307 EP 3315 DI 10.1038/onc.2013.291 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AK5DA UT WOS:000338443400010 PM 23995789 ER PT J AU Springman, AC Lacher, DW Waymire, EA Wengert, SL Singh, P Zadoks, RN Davies, HD Manning, SD AF Springman, Amber Cody Lacher, David W. Waymire, Emily A. Wengert, Samantha L. Singh, Pallavi Zadoks, Ruth N. Davies, H. Dele Manning, Shannon D. TI Pilus distribution among lineages of group b streptococcus: an evolutionary and clinical perspective SO BMC MICROBIOLOGY LA English DT Article DE Streptococcus agalactiae; Pilus; MLST; Molecular epidemiology ID MOLECULAR CHARACTERIZATION; ANTIMICROBIAL RESISTANCE; AGALACTIAE STRAINS; GENOME SEQUENCE; BOVINE; INFECTIONS; COLONIZATION; DIVERSITY; ISLANDS; GENOTYPES AB Background: Group B Streptococcus (GBS) is an opportunistic pathogen in both humans and bovines. Epidemiological and phylogenetic analyses have found strains belonging to certain phylogenetic lineages to be more frequently associated with invasive newborn disease, asymptomatic maternal colonization, and subclinical bovine mastitis. Pilus structures in GBS facilitate colonization and invasion of host tissues and play a role in biofilm formation, though few large-scale studies have estimated the frequency and diversity of the three pilus islands (PIs) across diverse genotypes. Here, we examined the distribution of pilus islands (PI) 1, 2a and 2b among 295 GBS strains representing 73 multilocus sequence types (STs) belonging to eight clonal complexes. PCR-based RFLP was also used to evaluate variation in the genes encoding pilus backbone proteins of PI-2a and PI-2b. Results: All 295 strains harbored one of the PI-2 variants and most human-derived strains contained PI-1. Bovine-derived strains lacked PI-1 and possessed a unique PI-2b backbone protein allele. Neonatal strains more frequently had PI-1 and a PI-2 variant than maternal colonizing strains, and most CC-17 strains had PI-1 and PI-2b with a distinct backbone protein allele. Furthermore, we present evidence for the frequent gain and loss of genes encoding certain pilus types. Conclusions: These data suggest that pilus combinations impact host specificity and disease presentation and that diversification often involves the loss or acquisition of PIs. Such findings have implications for the development of GBS vaccines that target the three pilus islands. C1 [Springman, Amber Cody; Waymire, Emily A.; Wengert, Samantha L.; Singh, Pallavi; Manning, Shannon D.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. [Lacher, David W.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [Zadoks, Ruth N.] Univ Glasgow, Inst Biodivers Anim Hlth & Comparat Med, Glasgow, Lanark, Scotland. [Zadoks, Ruth N.] Moredun Res Inst, Penicuik, Midlothian, Scotland. [Davies, H. Dele] Univ Nebraska, Sch Med, Omaha, NE USA. RP Manning, SD (reprint author), Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. EM mannin71@msu.edu OI Zadoks, Ruth/0000-0002-1164-8000; Singh, Pallavi/0000-0002-0283-7459; Manning, Shannon/0000-0001-9581-0660 FU National Institutes of Health [AI066081]; Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) FX This paper is dedicated to Cody Springman, who worked so hard on this project and passed away just prior to publication. We thank Jacob Sinkoff and Cassandra Martin for technical support, Drs. Nicola Jones and Martin Wiedmann for providing the bovine strains, and the late Dr. Thomas S. Whittam for his guidance and support. This study was supported by the National Institutes of Health [grant number AI066081] and the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS). NR 46 TC 10 Z9 10 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD JUN 19 PY 2014 VL 14 AR 159 DI 10.1186/1471-2180-14-159 PG 11 WC Microbiology SC Microbiology GA AK1GS UT WOS:000338164000001 PM 24943359 ER PT J AU Shieh, YC Tortorello, ML Fleischman, GJ Li, D Schaffner, DW AF Shieh, Y. Carol Tortorello, Mary Lou Fleischman, Gregory J. Li, Di Schaffner, Donald W. TI Tracking and modeling norovirus transmission during mechanical slicing of globe tomatoes SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Norovirus; Tomato; Mechanical slicing; Modeling; Transmission ID HEPATITIS-A VIRUS; IN-GROUND BEEF; LISTERIA-MONOCYTOGENES; CROSS-CONTAMINATION; MURINE NOROVIRUS; UNITED-STATES; FOOD; INTERRUPTION; SANITATION; ATTACHMENT AB Recent epidemiological evidence indicates that preparation of fresh produce for use as ingredients in ready-to-eat food in commercial settings has been a significant source of the norovirus (NoV) infections in the U.S. This research investigated the dissemination of NoV from a single tomato to many others via the use of an 11-horizontal blade slicer commonly found in restaurants or sandwich shops. A total of eight trials were conducted. The source of contamination in each trial was a soak-inoculated, air-dried globe tomato containing similar to 8 log10 murine norovirus (MNV). Each trial began by slicing a single un-inoculated tomato in the slicer, followed by slicing an inoculated tomato. This was then followed by slicing 9 to 27 un-inoculated tomatoes. A similar and constant hand pressure on the slicer was used in every trial. Three slices from each tomato were collected for virus elution, concentration, and extraction before RT-PCR detection of MNV. The change in MNV per sliced tomato was averaged over all eight trials, and two mathematical models were fit to the average data using a logarithmic model or a power model. Regression analysis determined that the equation that best fit the data was y = -0.903 * ln(x) + 7.945, where y = log10 MNV per slicing and x = tomato slicing number. An acceptable fit (R-2 = 0.913) was indicated. The MNV levels transferred (y) generally decreased as the number of tomatoes sliced (x) increased, with some exceptions. Infrequent but erratic transfers, where the MNV level of a subsequent tomato was higher than that of a preceding tomato, occurred in later transfer of some trials. In contrast, the first and second transfers of each trial were always shown to have sharply decreased levels of MNV from the inoculum. The MNV log10 reduction per slicing event changes throughout the process: with a predicted 0.63 log10 reduction from tomato 1 to tomato 2(76% reduction); a 0.07 log10 reduction predicted from tomato 13 to tomato 14 (a 14% reduction); and 0.03 log10 reduction predicted from tomato 27 to tomato 28 (a 7% reduction). Virus transfer is clearly variable even given the consistent slicing procedure used throughout each trial. This study illustrates the complex nature of risk prediction associated with NoV cross-contamination during food preparation in commercial establishments. Published by Elsevier B.V. C1 [Shieh, Y. Carol; Tortorello, Mary Lou; Fleischman, Gregory J.] US FDA, Div Food Proc Sci & Technol, Bedford Pk, IL 60501 USA. [Li, Di; Schaffner, Donald W.] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA. RP Shieh, YC (reprint author), 6502 S Archer Rd, Bedford Pk, IL 60501 USA. EM carol.shieh@fda.hhs.gov FU US FDA; USDA [2008-51110-04345] FX The authors thank FDA staff and student Tzu Yun Chang at Illinois Institute of Technology for the laboratory assistance in completing this study. The authors appreciate the comments provided by Diana Stewart and Richard McDonald at FDA. This research was funded in part by US FDA and USDA award no. 2008-51110-04345. NR 26 TC 1 Z9 1 U1 1 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 EI 1879-3460 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUN 16 PY 2014 VL 180 BP 13 EP 18 DI 10.1016/j.ijfoodmicro.2014.04.002 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA AI8VO UT WOS:000337205300003 PM 24769163 ER PT J AU Talaat, KR Luke, CJ Khurana, S Manischewitz, J King, LR McMahon, BA Karron, RA Lewis, KDC Qin, J Follmann, DA Golding, H Neuzil, KM Subbarao, K AF Talaat, Kawsar R. Luke, Catherine J. Khurana, Surender Manischewitz, Jody King, Lisa R. McMahon, Bridget A. Karron, Ruth A. Lewis, Kristen D. C. Qin, Jing Follmann, Dean A. Golding, Hana Neuzil, Kathleen M. Subbarao, Kanta TI A Live Attenuated Influenza A(H5N1) Vaccine Induces Long-Term Immunity in the Absence of a Primary Antibody Response SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE H5N1; avian influenza; live attenuated; vaccine ID A H5N1 VACCINE; HEALTHY-ADULTS; VIRUS VACCINE; PHASE-I; A/DUCK/SINGAPORE/97 VACCINE; MF59-ADJUVANTED INFLUENZA; ANTIGENIC VARIANT; IMMUNOGENICITY; SAFETY; HUMANS AB Background. Highly pathogenic avian influenza A(H5N1) causes severe infections in humans. We generated 2 influenza A(H5N1) live attenuated influenza vaccines for pandemic use (pLAIVs), but they failed to elicit a primary immune response. Our objective was to determine whether the vaccines primed or established long-lasting immunity that could be detected by administration of inactivated subvirion influenza A(H5N1) vaccine (ISIV). Methods. The following groups were invited to participate in the study: persons who previously received influenza A(H5N1) pLAIV; persons who previously received an irrelevant influenza A(H7N3) pLAIV; and community members who were naive to influenza A(H5N1) and LAIV. LAIV-experienced subjects received a single 45-mu g dose of influenza A(H5N1) ISIV. Influenza A(H5N1)- and LAIV-naive subjects received either 1 or 2 doses of ISIV. Results. In subjects who had previously received antigenically matched influenza A(H5N1) pLAIV followed by 1 dose of ISIV compared with those who were naive to influenza A(H5N1) and LAIV and received 2 doses of ISIV, we observed an increased frequency of antibody response (82% vs 50%, by the hemagglutination inhibition assay) and a significantly higher antibody titer (112 vs 76; P =.04). The affinity of antibody and breadth of cross-clade neutralization was also enhanced in influenza A(H5N1) pLAIV-primed subjects. Conclusions. ISIV administration unmasked long-lasting immunity in influenza A(H5N1) pLAIV recipients, with a rapid, high-titer, high-quality antibody response that was broadly cross-reactive across several influenza A(H5N1) clades. C1 [Talaat, Kawsar R.; McMahon, Bridget A.; Karron, Ruth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD USA. [Luke, Catherine J.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Qin, Jing; Follmann, Dean A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Khurana, Surender; Manischewitz, Jody; King, Lisa R.; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Lewis, Kristen D. C.; Neuzil, Kathleen M.] PATH, Seattle, WA USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; Influenza Vaccine Manufacturing Improvement Initiative of the Biomedical Advanced Research and Development Authority, US Department of Health and Human Services; PATH Vaccine Solutions; Center for Biologics Evaluation and Research, Food and Drug Administration FX This work was supported by the Intramural Research Program of National Institute of Allergy and Infectious Diseases, National Institutes of Health; the Influenza Vaccine Manufacturing Improvement Initiative of the Biomedical Advanced Research and Development Authority, US Department of Health and Human Services; PATH Vaccine Solutions; and Pandemic Flu Funding from the Center for Biologics Evaluation and Research, Food and Drug Administration. NR 35 TC 38 Z9 39 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2014 VL 209 IS 12 BP 1860 EP 1869 DI 10.1093/infdis/jiu123 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AI7JB UT WOS:000337063100002 PM 24604819 ER PT J AU Chappell, G Kutanzi, K Uehara, T Tryndyak, V Hong, HH Hoenerhoff, M Beland, FA Rusyn, I Pogribny, IP AF Chappell, Grace Kutanzi, Kristy Uehara, Takeki Tryndyak, Volodymyr Hong, Hue-Hua Hoenerhoff, Mark Beland, Frederick A. Rusyn, Ivan Pogribny, Igor P. TI Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE mouse; liver carcinogenesis; DNA methylation; genetics; epigenetics; histone lysine methylation ID TUMOR-SUPPRESSOR GENE; HEPATOCELLULAR-CARCINOMA; DNA METHYLATION; BETA-CATENIN; MOLECULAR-MECHANISMS; SOMATIC MUTATIONS; HUMAN CANCERS; LIVER-TUMORS; CPG ISLANDS; MOUSE AB Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and is rising in incidence worldwide. The molecular mechanisms leading to the development of HCC are complex and include both genetic and epigenetic events. To determine the relative contribution of these alterations in liver tumorigenesis, we evaluated epigenetic modifications at both global and gene specific levels, as well as the mutational profile of genes commonly altered in liver tumors. A mouse model of fibrosis-associated liver cancer that was designed to emulate cirrhotic liver, a prevailing disease state observed in most humans with HCC, was used. Tumor and nontumor liver samples from B6C3F1 mice treated with N-nitrosodiethylamine (DEN; a single ip injection of 1 mg/kg at 14 days of age) and carbon tetrachloride (CCl4; 0.2 ml/kg, 2 times/week ip starting at 8 weeks of age for 14 weeks), as well as corresponding vehicle control animals, were analyzed for genetic and epigenetic alterations. H-ras, Ctnnb1 and Hnf1 alpha genes were not mutated in tumors in mice treated with DEN+CCl4. In contrast, the increased tumor incidence in mice treated with DEN+CCl4 was associated with marked epigenetic changes in liver tumors and nontumor liver tissue, including demethylation of genomic DNA and repetitive elements, a decrease in histone 3 lysine 9 trimethylation (H3K9me3) and promoter hypermethylation and functional downregulation of Riz1, a histone lysine methyltransferase tumor suppressor gene. Additionally, the reduction in H3K9me3 was accompanied by increased expression of long interspersed nucleotide elements 1 and short interspersed nucleotide elements B2, which is an indication of genomic instability. In summary, our results suggest that epigenetic events, rather than mutations in known cancer-related genes, play a prominent role in increased incidence of liver tumors in this mouse model of fibrosis-associated liver cancer. C1 [Chappell, Grace; Uehara, Takeki; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. [Kutanzi, Kristy; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Hong, Hue-Hua; Hoenerhoff, Mark] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Hong, Hue-Hua; Hoenerhoff, Mark] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM iir@unc.edu; igor.pogribny@fda.hhs.gov RI Rusyn, Ivan/S-2426-2016 FU National Institutes of Health [R01 ES015241, P42 ES005948, R01 ES023195] FX Grant sponsor: National Institutes of Health; Grant numbers: R01 ES015241, P42 ES005948 and R01 ES023195 NR 49 TC 11 Z9 12 U1 0 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2014 VL 134 IS 12 BP 2778 EP 2788 DI 10.1002/ijc.28610 PG 11 WC Oncology SC Oncology GA AE1SU UT WOS:000333751000004 PM 24242335 ER PT J AU Santana-Quintero, L Dingerdissen, H Thierry-Mieg, J Mazumder, R Simonyan, V AF Santana-Quintero, Luis Dingerdissen, Hayley Thierry-Mieg, Jean Mazumder, Raja Simonyan, Vahan TI HIVE-Hexagon: High-Performance, Parallelized Sequence Alignment for Next-Generation Sequencing Data Analysis SO PLOS ONE LA English DT Article ID GENOME; ALGORITHMS; PROTEINS; SEARCH; SITES; TOOL AB Due to the size of Next-Generation Sequencing data, the computational challenge of sequence alignment has been vast. Inexact alignments can take up to 90% of total CPU time in bioinformatics pipelines. High-performance Integrated Virtual Environment (HIVE), a cloud-based environment optimized for storage and analysis of extra-large data, presents an algorithmic solution: the HIVE-hexagon DNA sequence aligner. HIVE-hexagon implements novel approaches to exploit both characteristics of sequence space and CPU, RAM and Input/Output (I/O) architecture to quickly compute accurate alignments. Key components of HIVE-hexagon include non-redundification and sorting of sequences; floating diagonals of linearized dynamic programming matrices; and consideration of cross-similarity to minimize computations. C1 [Santana-Quintero, Luis; Dingerdissen, Hayley; Simonyan, Vahan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Dingerdissen, Hayley; Mazumder, Raja] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Thierry-Mieg, Jean] NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, Bethesda, MD 20892 USA. RP Mazumder, R (reprint author), George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. EM mazumder@gwu.edu; Vahan.Simonyan@fda.hhs.gov RI THIERRY-MIEG, Jean/F-1975-2017 OI THIERRY-MIEG, Jean/0000-0002-0396-6789 FU Food and Drug Administration Medical Countermeasures Initiative; Intramural Research Program of the NIH, National Library of Medicine FX This research was supported in part by the Food and Drug Administration Medical Countermeasures Initiative and in part by Intramural Research Program of the NIH, National Library of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 8 Z9 8 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 11 PY 2014 VL 9 IS 6 AR e99033 DI 10.1371/journal.pone.0099033 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AK7TQ UT WOS:000338631000043 PM 24918764 ER PT J AU Kheradmand, E Rafii, F Yazdi, MH Sepahi, AA Shahverdi, AR Oveisi, MR AF Kheradmand, Erfan Rafii, Fatemeh Yazdi, Mohammad Hossien Sepahi, Abas Akhavan Shahverdi, Ahmad Reza Oveisi, Mohammad Reza TI The antimicrobial effects of selenium nanoparticle-enriched probiotics and their fermented broth against Candida albicans SO DARU-JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Candida albicans; Secretory products; Selenium nanoparticles; Antimicrobial effect; Lactobacillus plantarum; Lactobacillus johnsonii ID LACTIC-ACID BACTERIA; COLONIZATION; STRAINS AB Background: Lactic acid bacteria are considered important probiotics for prevention of some infections. The aim of this work was to investigate the effect of selenium dioxide on the antifungal activity of Lactobacillus plantarum and L. johnsonii against Candida albicans. Methods: Lactobacillus plantarum and L. johnsonii cells, grown in the presence and absence of selenium dioxide, and their cell-free spent culture media were tested for antifungal activity against C. albicans ATCC 14053 by a hole-plate diffusion method and a time-kill assay. Results: Both L. plantarum and L. johnsonii reduced selenium dioxide to cell-associated elemental selenium nanoparticles. The cell-free spent culture media, from both Lactobacillus species that had been grown with selenium dioxide for 48 h, showed enhanced antifungal activity against C. albicans. Enhanced antifungal activity of cell biomass against C. albicans was also observed in cultures grown with selenium dioxide. Conclusions: Selenium dioxide-treated Lactobacillus spp. or their cell-free spent broth inhibited the growth of C. albicans and should be investigated for possible use in anti-Candida probiotic formulations in future. C1 [Kheradmand, Erfan; Yazdi, Mohammad Hossien; Shahverdi, Ahmad Reza] Univ Tehran Med Sci, Fac Pharm, Dept Pharmaceut Biotechnol, Tehran, Iran. [Kheradmand, Erfan; Yazdi, Mohammad Hossien; Shahverdi, Ahmad Reza] Univ Tehran Med Sci, Fac Pharm, Biotechnol Res Ctr, Tehran, Iran. [Kheradmand, Erfan; Sepahi, Abas Akhavan] Azad Univ, Sci & Res Branch, Tehran, Iran. [Rafii, Fatemeh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Shahverdi, Ahmad Reza] Univ Tehran Med Sci, Sch Adv Med Technol, Dept Med Biotechnol, Tehran, Iran. [Oveisi, Mohammad Reza] Univ Tehran Med Sci, Fac Pharm, Dept Food & Drug Control, Tehran, Iran. RP Shahverdi, AR (reprint author), Univ Tehran Med Sci, Fac Pharm, Dept Pharmaceut Biotechnol, Tehran, Iran. EM shahverd@tums.ac.ir RI Yazdi, Mohammad Hossein/N-7144-2016 OI Yazdi, Mohammad Hossein/0000-0001-8567-8555 FU Tehran University of Medical Sciences, Tehran, Iran FX This work was supported by the Deputy of Research, Tehran University of Medical Sciences, Tehran, Iran. There is no conflict of interest for authors in this work. The views presented in this article do not necessarily reflect those of the U. S. Food and Drug Administration. NR 20 TC 9 Z9 10 U1 2 U2 26 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1560-8115 J9 DARU JI DARU PD JUN 6 PY 2014 VL 22 AR 48 DI 10.1186/2008-2231-22-48 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ0EY UT WOS:000337323900001 PM 24906455 ER PT J AU Feng, SX Chiesa, OA Kijak, P Chattopadhaya, C Lancaster, V Smith, EA Girard, L Sklenka, S Li, H AF Feng, Shixia Chiesa, Oscar A. Kijak, Philip Chattopadhaya, Chaitali Lancaster, Vicki Smith, Elizabeth A. Girard, Lauren Sklenka, Sara Li, Hui TI Determination of Ceftiofur Metabolite Desfuroylceftiofur Cysteine Disulfide in Bovine Tissues Using Liquid Chromatography-Tandem Mass Spectrometry as a Surrogate Marker Residue for Ceftiofur SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE ceftiofur; desfuroylceftiofur cysteine disulfide; bovine tissues; LC-MS/MS ID BETA-LACTAM ANTIBIOTICS; SOLID-PHASE EXTRACTION; LC-MS/MS; VETERINARY DRUGS; KIDNEY TISSUE; MUSCLE; VALIDATION; POULTRY; MILK AB Ceftiofur is a widely used cephalosporin beta-lactam antibiotic with frequently reported residue violations. This paper reports a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining a ceftiofur metabolite, desfuroylceftiofur cysteine disulfide (DCCD), in bovine kidney, liver, and muscle tissues. Incurred tissue samples were obtained from dosed animals and analyzed to evaluate the utility of the method. For kidney, the target tissue, the method utilized a simple extraction with phosphate buffer followed by solid phase extraction (SPE) cleanup. For liver and muscle, acetonitrile and hexane were used to remove most proteins and fat from the initial buffer extract before the SPE cleanup. Method accuracy was between 97 and 107%, and the coefficient of variation was between 3.4 and 11.0% for all three types of tissues. The relationship between the new and regulatory methods for bovine kidney was established. It was concluded that DCCD is a suitable surrogate marker residue for ceftiofur in bovine kidney. C1 [Feng, Shixia; Chiesa, Oscar A.; Kijak, Philip; Chattopadhaya, Chaitali; Smith, Elizabeth A.; Girard, Lauren; Sklenka, Sara; Li, Hui] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Lancaster, Vicki] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Li, H (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM hui.li@fda.hhs.gov NR 30 TC 8 Z9 8 U1 1 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 4 PY 2014 VL 62 IS 22 BP 5011 EP 5019 DI 10.1021/jf405423e PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA AI6WW UT WOS:000337018700005 PM 24819974 ER PT J AU Jablonski, JE Moore, JC Harnly, JM AF Jablonski, Joseph E. Moore, Jeffrey C. Harnly, James M. TI Nontargeted Detection of Adulteration of Skim Milk Powder with Foreign Proteins Using UHPLC-UV SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE skim milk powder; economic adulteration; ultrahigh-performance liquid chromatography ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; GEL-ELECTROPHORESIS; IDENTIFICATION; QUANTIFICATION AB Chromatographic profiles of skim milk powder (SMP) and mixtures of SMP with soy (SPI), pea (PPI), brown rice (BRP), and hydrolyzed wheat protein (HWPI) isolates were obtained by ultrahigh-performance liquid chromatography (UHPLC) with 215 nm detection. Two data analysis approaches were compared for their utility to classify samples as authentic or adulterated. The t test approach evaluated data points exceeding the 99% confidence limit of the mean authentic SMP chromatogram and used data points from the entire chromatogram. The other approach used the multivariate Q statistic from a SIMCA model of authentic samples to determine adulteration and used a selected retention window to obtain best classifications. Q-Statistic and t test correctly classified adulteration of SMP with SPI at the 1% and 3% levels, respectively, while minimizing false classifications of authentic SMP. Detection of SMP adulterated with PPI, BRP, and HWPI was possible at higher adulteration levels. C1 [Jablonski, Joseph E.] US FDA, Ctr Food Safety & Appl Nutr, Div Food Proc Sci & Technol, Bedford Pk, IL 60501 USA. [Jablonski, Joseph E.; Moore, Jeffrey C.] US Pharmacopeial Convent Inc, Rockville, MD 20852 USA. [Harnly, James M.] ARS, Food Composit & Methods Dev Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. RP Jablonski, JE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Food Proc Sci & Technol, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM joseph.jablonski@fda.hhs.gov NR 29 TC 9 Z9 9 U1 3 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 4 PY 2014 VL 62 IS 22 BP 5198 EP 5206 DI 10.1021/jf404924x PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA AI6WW UT WOS:000337018700027 PM 24811490 ER PT J AU Dingerdissen, H Weaver, DS Karp, PD Pan, Y Simonyan, V Mazumder, R AF Dingerdissen, Hayley Weaver, Daniel S. Karp, Peter D. Pan, Yang Simonyan, Vahan Mazumder, Raja TI A framework for application of metabolic modeling in yeast to predict the effects of nsSNV in human orthologs SO BIOLOGY DIRECT LA English DT Article DE nsSNV; Ortholog; Sequence conservation; FBA; Yeast metabolic modeling ID TRANSFER-RNA SYNTHETASE; METHIONINE SALVAGE PATHWAY; ERYTHROPOIETIC PROTOPORPHYRIA; SACCHAROMYCES-CEREVISIAE; ACTIVE-SITE; HUMAN FERROCHELATASE; WINCHESTER-SYNDROME; ENZYME-ACTIVITY; GENE; MUTATIONS AB Background: We have previously suggested a method for proteome wide analysis of variation at functional residues wherein we identified the set of all human genes with nonsynonymous single nucleotide variation (nsSNV) in the active site residue of the corresponding proteins. 34 of these proteins were shown to have a 1:1:1 enzyme: pathway: reaction relationship, making these proteins ideal candidates for laboratory validation through creation and observation of specific yeast active site knock-outs and downstream targeted metabolomics experiments. Here we present the next step in the workflow toward using yeast metabolic modeling to predict human metabolic behavior resulting from nsSNV. Results: For the previously identified candidate proteins, we used the reciprocal best BLAST hits method followed by manual alignment and pathway comparison to identify 6 human proteins with yeast orthologs which were suitable for flux balance analysis (FBA). 5 of these proteins are known to be associated with diseases, including ribose 5-phosphate isomerase deficiency, myopathy with lactic acidosis and sideroblastic anaemia, anemia due to disorders of glutathione metabolism, and two porphyrias, and we suspect the sixth enzyme to have disease associations which are not yet classified or understood based on the work described herein. Conclusions: Preliminary findings using the Yeast 7.0 FBA model show lack of growth for only one enzyme, but augmentation of the Yeast 7.0 biomass function to better simulate knockout of certain genes suggested physiological relevance of variations in three additional proteins. Thus, we suggest the following four proteins for laboratory validation: delta-aminolevulinic acid dehydratase, ferrochelatase, ribose-5 phosphate isomerase and mitochondrial tyrosyl-tRNA synthetase. This study indicates that the predictive ability of this method will improve as more advanced, comprehensive models are developed. Moreover, these findings will be useful in the development of simple downstream biochemical or mass-spectrometric assays to corroborate these predictions and detect presence of certain known nsSNVs with deleterious outcomes. Results may also be useful in predicting as yet unknown outcomes of active site nsSNVs for enzymes that are not yet well classified or annotated. C1 [Dingerdissen, Hayley; Pan, Yang; Mazumder, Raja] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Weaver, Daniel S.; Karp, Peter D.] SRI Int, Ctr Artificial Intelligence, Bioinformat Res Grp, Menlo Pk, CA 94025 USA. [Simonyan, Vahan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Mazumder, Raja] George Washington Univ, McCormick Genom & Prote Ctr, Washington, DC 20037 USA. RP Mazumder, R (reprint author), George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Ross Hall,Room 540,2300 Eye St NW, Washington, DC 20037 USA. EM mazumder@gwu.edu OI Karp, Peter/0000-0002-5876-6418; Pan, Yang/0000-0003-3487-7233 FU George Washington University; Center for Biologics Evaluation and Research FX We would like to thank Akos Vertes, Ph.D., Professor of Chemistry, Biochemistry and Molecular Biology at the George Washington University, for discussion and insight in the direction of this effort. Computations were performed at High-performance Integrated Virtual Environment (HIVE) located at The George Washington University and co-developed by Dr. Mazumder and Dr. Simonyan and at the Bioinformatics Research Group at SRI International, directed by Peter Karp. Support for this work came from The George Washington University funds to RM. This project is also supported in part by an appointment to the Research Participation program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 82 TC 1 Z9 1 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD JUN 3 PY 2014 VL 9 AR 9 DI 10.1186/1745-6150-9-9 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AK4AH UT WOS:000338365900001 PM 24894379 ER PT J AU Abunimer, A Smith, K Wu, TJ Lam, P Simonyan, V Mazumder, R AF Abunimer, Ayman Smith, Krista Wu, Tsung-Jung Lam, Phuc Simonyan, Vahan Mazumder, Raja TI Single-Nucleotide Variations in Cardiac Arrhythmias: Prospects for Genomics and Proteomics Based Biomarker Discovery and Diagnostics SO Genes LA English DT Article DE cardiac arrhythmia; SNP; genome-wide association; proteomics; next-generation sequencing; S-nitrosylation; cysteine; nsSNV; biocuration ID LONE ATRIAL-FIBRILLATION; S-NITROSYLATION; NITRIC-OXIDE; COMMON VARIANTS; HEART-FAILURE; HYPERTROPHIC CARDIOMYOPATHY; VENTRICULAR-ARRHYTHMIAS; MISSENSE MUTATIONS; MESSENGER-RNA; QT INTERVAL AB Cardiovascular diseases are a large contributor to causes of early death in developed countries. Some of these conditions, such as sudden cardiac death and atrial fibrillation, stem from arrhythmias-a spectrum of conditions with abnormal electrical activity in the heart. Genome-wide association studies can identify single nucleotide variations (SNVs) that may predispose individuals to developing acquired forms of arrhythmias. Through manual curation of published genome-wide association studies, we have collected a comprehensive list of 75 SNVs associated with cardiac arrhythmias. Ten of the SNVs result in amino acid changes and can be used in proteomic-based detection methods. In an effort to identify additional non-synonymous mutations that affect the proteome, we analyzed the post-translational modification S-nitrosylation, which is known to affect cardiac arrhythmias. We identified loss of seven known S-nitrosylation sites due to non-synonymous single nucleotide variations (nsSNVs). For predicted nitrosylation sites we found 1429 proteins where the sites are modified due to nsSNV. Analysis of the predicted S-nitrosylation dataset for over-or under-representation (compared to the complete human proteome) of pathways and functional elements shows significant statistical over-representation of the blood coagulation pathway. Gene Ontology (GO) analysis displays statistically over-represented terms related to muscle contraction, receptor activity, motor activity, cystoskeleton components, and microtubule activity. Through the genomic and proteomic context of SNVs and S-nitrosylation sites presented in this study, researchers can look for variation that can predispose individuals to cardiac arrhythmias. Such attempts to elucidate mechanisms of arrhythmia thereby add yet another useful parameter in predicting susceptibility for cardiac diseases. C1 [Abunimer, Ayman; Smith, Krista; Wu, Tsung-Jung; Mazumder, Raja] George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA. [Lam, Phuc; Simonyan, Vahan] Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Mazumder, Raja] George Washington Univ, McCormick Genom & Prote Ctr, Washington, DC 20037 USA. RP Mazumder, R (reprint author), George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA. EM aabunimer115@gmail.com; ksmith7@gwu.edu; sunearth@gwu.edu; phuclam87@gmail.com; Vahan.Simonyan@fda.hhs.go; mazumder@gwu.edu FU Research Participation Program at the Center for Biologics Evaluation and Research FX This project is supported in part by Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 64 TC 3 Z9 3 U1 1 U2 7 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2073-4425 J9 GENES-BASEL JI Genes PD JUN PY 2014 VL 5 IS 2 BP 254 EP 269 DI 10.3390/genes5020254 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA CA4ET UT WOS:000348857700001 PM 24705329 ER PT J AU Skoog, SA Nguyen, AK Kumar, G Zheng, JW Goering, PL Koroleva, A Chichkov, BN Narayan, RJ AF Skoog, Shelby A. Nguyen, Alexander K. Kumar, Girish Zheng, Jiwen Goering, Peter L. Koroleva, Anastasia Chichkov, Boris N. Narayan, Roger J. TI Two-photon polymerization of 3-D zirconium oxide hybrid scaffolds for long-term stem cell growth SO BIOINTERPHASES LA English DT Article ID MICROFABRICATION; REGENERATION; SHRINKAGE; MIGRATION; ADHESION; CULTURE; SHAPE; FATE AB Two-photon polymerization is a technique that involves simultaneous absorption of two photons from a femtosecond laser for selective polymerization of a photosensitive material. In this study, two-photon polymerization was used for layer-by-layer fabrication of 3-D scaffolds composed of an inorganic-organic zirconium oxide hybrid material. Four types of scaffold microarchitectures were created, which exhibit layers of parallel line features at various orientations as well as pores between the line features. Long-term cell culture studies involving human bone marrow stromal cells were conducted using these 3-D scaffolds. Cellular adhesion and proliferation were demonstrated on all of the scaffold types; tissuelike structure was shown to span the pores. This study indicates that two-photon polymerization may be used to create microstructured scaffolds out of an inorganic-organic zirconium oxide hybrid material for use in 3-D tissue culture systems. (C) 2014 American Vacuum Society. C1 [Skoog, Shelby A.; Nguyen, Alexander K.; Narayan, Roger J.] Univ North Carolina Chapel Hill, Joint Dept Biomed Engn, Raleigh, NC 27965 USA. [Skoog, Shelby A.; Nguyen, Alexander K.; Narayan, Roger J.] N Carolina State Univ, Raleigh, NC 27965 USA. [Skoog, Shelby A.; Kumar, Girish; Zheng, Jiwen; Goering, Peter L.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Nguyen, Alexander K.; Koroleva, Anastasia; Chichkov, Boris N.] Laser Zentrum Hannover eV, Dept Nanotechnol, D-30419 Hannover, Germany. RP Narayan, RJ (reprint author), Univ North Carolina Chapel Hill, Joint Dept Biomed Engn, Raleigh, NC 27965 USA. EM roger_narayan@ncsu.edu RI Chichkov, Boris/M-4112-2015 FU U.S. National Science Foundation [1041375] FX The authors would like to acknowledge the FDA White Oak Nanotechnology Core Facility for instrument use and scientific and technical assistance. In addition, the authors would like to acknowledge financial support from U.S. National Science Foundation Award #1041375. The authors would also like to thank the Laser Zentrum Hannover (LZH) in Hannover, Germany for use of their two-photon polymerization system for fabrication procedures. A. K. and B.N.C. acknowledge support by the German Research Foundation Cluster of Excellence Rebirth "From Regenerative Biology to Reconstructive Therapy"and the Lower Saxony project "Biofabrication for NIFE."The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 39 TC 4 Z9 5 U1 2 U2 38 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1934-8630 EI 1559-4106 J9 BIOINTERPHASES JI Biointerphases PD JUN PY 2014 VL 9 IS 2 DI 10.1116/1.4873688 PG 7 WC Biophysics; Materials Science, Biomaterials SC Biophysics; Materials Science GA AM4IM UT WOS:000339817200014 PM 24985218 ER PT J AU Cao, XF Mittelstaedt, RA Pearce, MG Allen, BC Soeteman-Hernandez, LG Johnson, GE Bigger, CAH Heflich, RH AF Cao, Xuefei Mittelstaedt, Roberta A. Pearce, Mason G. Allen, Bruce C. Soeteman-Hernandez, Lya G. Johnson, George E. Bigger, C. Anita H. Heflich, Robert H. TI Quantitative Dose-Response Analysis of Ethyl Methanesulfonate Genotoxicity in Adult gpt-delta Transgenic Mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE benchmark dose; threshold; NOGEL; bilinear model; gene mutation; gpt; micronucleus; Pig-a; dose-response ID PIG-A GENE; RED-BLOOD-CELLS; SPLEEN T-CELLS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; IN-VIVO; MUTATION ASSAY; SOMATIC MUTATION; N-NITROSOUREA; RATS; THRESHOLD AB The assumption that mutagens have linear dose-responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA-reactive mutagen and carcinogen, exhibited sublinear or thresholded dose-responses for LacZ mutation in transgenic Muta (TM) Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Muller L [2009]: Mutat Res 678: 101-107). In order to explore variables in establishing genotoxicity dose-responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta (TM) Mouse. Male gpt-delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig-a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i. e., no-observed-genotoxic-effect-levels (NOGELs), lower confidence limits of threshold effect levels (Td-LCIs), and lower confidence limits of 10% benchmark response rates (BMDL(10)s). Similar PoDs were calculated from the published EMS dose-responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig-a MFs were 13-40-fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose-responses in gpt-delta mice had lower PoDs than those calculated from the Muta (TM) Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds. (C) 2014 Wiley Periodicals, Inc. C1 [Cao, Xuefei; Mittelstaedt, Roberta A.; Pearce, Mason G.; Heflich, Robert H.] US FDA, NCTR, Jefferson, AR 72079 USA. [Allen, Bruce C.] Bruce Allen Consulting, Chapel Hill, NC USA. [Soeteman-Hernandez, Lya G.] Natl Inst Publ Hlth & Environm, Ctr Hlth Protect, NL-3720 BA Bilthoven, Netherlands. [Johnson, George E.] Swansea Univ, Coll Med, Inst Life Sci, Swansea, W Glam, Wales. [Bigger, C. Anita H.] Bigger Consulting, St Augustine, FL USA. RP Heflich, RH (reprint author), US FDA, NCTR, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM robert.heflich@fda.hhs.gov OI Johnson, George/0000-0001-5643-9942 FU Commissioner's Fellowship Program of the U.S. FDA FX Grant sponsor: Commissioner's Fellowship Program of the U.S. FDA (to X.C.). NR 60 TC 11 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2014 VL 55 IS 5 BP 385 EP 399 DI 10.1002/em.21854 PG 15 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA AL4MX UT WOS:000339108200002 PM 24535894 ER PT J AU Lee, HW Wang, HT Weng, MW Hu, Y Chen, WS Chou, D Liu, Y Donin, N Huang, WC Lepor, H Wu, XR Wang, HL Beland, FA Tang, MS AF Lee, Hyun-Wook Wang, Hsiang-Tsui Weng, Mao-wen Hu, Yu Chen, Wei-sheng Chou, David Liu, Yan Donin, Nicholas Huang, William C. Lepor, Herbert Wu, Xue-Ru Wang, Hailin Beland, Frederick A. Tang, Moon-shong TI Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells SO ONCOTARGET LA English DT Article DE Bladder cancer; 4-aminobiphenyl; Acrolein; DNA repair; Mutagenesis ID HUMAN URINARY-BLADDER; HUMAN P53 GENE; UBIQUITIN-PROTEASOME PATHWAY; CARCINOGEN-DNA ADDUCTS; MUTATIONAL HOTSPOTS; LIPID-PEROXIDATION; RAS PROTOONCOGENE; SEQUENCE CONTEXT; CANCER; REPAIR AB Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS. C1 [Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-wen; Hu, Yu; Chen, Wei-sheng; Chou, David; Tang, Moon-shong] NYU, Dept Environm Med, Sch Med, Tuxedo Pk, NY 10987 USA. [Liu, Yan; Donin, Nicholas; Huang, William C.; Lepor, Herbert; Wu, Xue-Ru] NYU, Sch Med, Dept Urol, New York, NY 10003 USA. [Wang, Hailin] Chinese Acad Sci, Ecoenvironm Sci Res Ctr, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Tang, MS (reprint author), NYU, Dept Environm Med, Sch Med, Tuxedo Pk, NY 10987 USA. EM moon-shong.tang@nyumc.org FU National Institutes of Health [CA114541, ES014641, CA99007, ES00260]; New York University School of Medicine Urology Department Philanthropic Fund FX This work was supported by National Institutes of Health grants [CA114541, ES014641, CA99007 and ES00260], and New York University School of Medicine Urology Department Philanthropic Fund. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. Funding for open access charge: New York University School of Medicine Urology Department Philanthropic Fund. NR 63 TC 9 Z9 10 U1 1 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JUN PY 2014 VL 5 IS 11 BP 3526 EP 3540 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AL3UG UT WOS:000339054500010 PM 24939871 ER PT J AU Liu, J Chan-Tack, KM Jadhav, P Seo, S Robertson, SM Kraft, J Singer, ME Struble, KA Arya, V AF Liu, Jiang Chan-Tack, Kirk M. Jadhav, Pravin Seo, Shirley Robertson, Sarah M. Kraft, Jeffrey Singer, Mary E. Struble, Kimberly A. Arya, Vikram TI Why did the FDA approve efavirenz 800 mg when co-administered with rifampin? SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE tuberculosis; HIV; rifampin; efavirenz; drug interaction ID HIV-INFECTED PATIENTS; PHARMACOKINETIC INTERACTIONS; ANTIRETROVIRAL THERAPY; 600 MG/DAY; TUBERCULOSIS; VARIABILITY; NEVIRAPINE; OUTCOMES AB Objectives: Literature reports regarding the efficacy of efavirenz (EFV) 600 mg with rifampin (RIF) are not consistent. Evaluation of a drug-drug interaction (DDI) study and supportive semi-mechanistic population pharmacokinetic (PK) analyses were undertaken to help delineate this issue. Design/Methods: DDI study and supportive semi-mechanistic population PK analyses were provided by BMS. Population PK analysis was based on six studies with intensive EFV PK sampling. An ACTG study with sparse PK sampling was used for model evaluation. Simulations compared EFV exposure at various doses in combination with RIF to EFV exposures at 600 mg once daily (QD). Effects of CYP2B6 genotypes on the magnitude of EFV-RIF interaction were also explored. Results: In DDI study, co-administering EFV 600 mg QD and RIP reduced mean EFV exposure by similar to 30%. Population PK model provided acceptable predictive performance of central tendency and variability for EFV C-0, C-max and AUC. Simulations predicted that increasing EFV to 800 mg QD with RIP would result in EFV AUC and C-max similar to EFV 600 mg QD alone. EFV AUC and Cmax were similar to 2 times higher in subjects with reduced function CYP2B6 genotypes. However, the RIP effect was consistent across all genotypes. EFV dose adjustment to 800 mg QD did not increase the risk of overexposure compared to 600 mg EFV QD within each genotype. Conclusion: Dose adjustment based on matching systemic exposure was recommended to mitigate the potential for sub-therapeutic EFV exposures. Our review did not reveal any safety concerns in subjects receiving EFV 800 mg QD with RIF. C1 [Liu, Jiang; Jadhav, Pravin] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Chan-Tack, Kirk M.; Singer, Mary E.; Struble, Kimberly A.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Seo, Shirley; Robertson, Sarah M.; Kraft, Jeffrey; Arya, Vikram] US FDA, Div Clin Pharmacol 4, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Chan-Tack, KM (reprint author), WO 22,Room 6337,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Kirk.Chan-Tack@fda.hhs.gov NR 32 TC 2 Z9 2 U1 1 U2 3 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD JUN PY 2014 VL 52 IS 6 BP 446 EP 453 DI 10.5414/CP202079 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK9MV UT WOS:000338752100002 PM 24755134 ER PT J AU Wang, Y Harigaya, Y Coll, MC AF Wang, Y. Harigaya, Y. Coll, M. Cavaille TI A Pharmacometric Approach to Support a Treatment Effect of Everolimus in Liver Transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Wang, Y.; Harigaya, Y.; Coll, M. Cavaille] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA A442 BP 713 EP 713 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033303191 ER PT J AU Chen, S Melchior, WB Wu, YF Guo, L AF Chen, Si Melchior, William B., Jr. Wu, Yuanfeng Guo, Lei TI Autophagy in drug-induced liver toxicity SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE autophagy; drug-induced liver toxicity ID ACETAMINOPHEN-INDUCED HEPATOTOXICITY; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; USNIC-ACID; CELL-DEATH; MONITORING AUTOPHAGY; OXIDATIVE STRESS; HEPATIC CELLS; MITOCHONDRIAL DYSFUNCTION; HEPG2 CELLS AB Liver injury resulting from exposure to drugs and chemicals is a major health problem. Autophagy is an important factor in a wide range of diseases, such as cancer, liver disease, muscular disorder, neurodegeneration, pathogen infection, and aging, and emerging evidence indicates that autophagy makes a substantial contribution to the pathogenesis of drug- and chemical-induced liver toxicity. In this review, we summarize current knowledge on autophagy triggered by toxicants/toxins, the protective role of autophagy in liver toxicity, and the underlying molecular mechanisms. We also highlight experimental approaches for studying autophagy. Copyright (C) 2014, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Chen, Si; Melchior, William B., Jr.; Wu, Yuanfeng; Guo, Lei] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, S (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, HFT 110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Si.Chen@fda.hhs.gov RI Wu, Yuanfeng/O-2920-2014 OI Wu, Yuanfeng/0000-0001-6390-3635 FU Postgraduate Research Program at the National Center for Toxicological Research; US Department of Energy; US Food and Drug Authority (FDA) FX Si Chen and Yuanfeng Wu were supported by appointments to the Postgraduate Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science Education, through an interagency agreement between the US Department of Energy and the US Food and Drug Authority (FDA). This article is not an official guidance or policy statement of the US FDA. No official support or endorsement by the US FDA is intended or should be inferred. NR 84 TC 2 Z9 2 U1 3 U2 19 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD JUN PY 2014 VL 22 IS 2 BP 161 EP 168 DI 10.1016/j.jfda.2014.03.007 PG 8 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AJ8YE UT WOS:000337993200001 ER PT J AU Yoo, SS Jorgensen, TJ Kennedy, AR Boice, JD Shapiro, A Hu, TCC Moyer, BR Grace, MB Kelloff, GJ Fenech, M Prasanna, PGS Coleman, CN AF Yoo, Stephen S. Jorgensen, Timothy J. Kennedy, Ann R. Boice, John D., Jr. Shapiro, Alla Hu, Tom C-C Moyer, Brian R. Grace, Marcy B. Kelloff, Gary J. Fenech, Michael Prasanna, Pataje G. S. Coleman, C. Norman TI Mitigating the risk of radiation-induced cancers: limitations and paradigms in drug development SO JOURNAL OF RADIOLOGICAL PROTECTION LA English DT Review DE radiation-induced cancer; radiation mitigator; radioprotector; radiation risk ID PERIPHERAL-BLOOD LYMPHOCYTES; DICENTRIC CHROMOSOME ASSAY; GRADE PROSTATE-CANCER; BOWMAN-BIRK INHIBITOR; PHOSPHORIBOSYL TRANSFERASE LOCUS; NUTRITION INTERVENTION TRIALS; SPORADIC COLORECTAL ADENOMAS; DISEASE-SPECIFIC MORTALITY; BLOCK MICRONUCLEUS ASSAY; ATM-DEFICIENT MICE AB The United States radiation medical countermeasures (MCM) programme for radiological and nuclear incidents has been focusing on developing mitigators for the acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and biodosimetry technologies to provide radiation dose assessments for guiding treatment. Because a nuclear accident or terrorist incident could potentially expose a large number of people to low to moderate doses of ionising radiation, and thus increase their excess lifetime cancer risk, there is an interest in developing mitigators for this purpose. This article discusses the current status, issues, and challenges regarding development of mitigators against radiation-induced cancers. The challenges of developing mitigators for ARS include: the long latency between exposure and cancer manifestation, limitations of animal models, potential side effects of the mitigator itself, potential need for long-term use, the complexity of human trials to demonstrate effectiveness, and statistical power constraints for measuring health risks (and reduction of health risks after mitigation) following relatively low radiation doses (< 0 :75 Gy). Nevertheless, progress in the understanding of the molecular mechanisms resulting in radiation injury, along with parallel progress in dose assessment technologies, make this an opportune, if not critical, time to invest in research strategies that result in the development of agents to lower the risk of radiation-induced cancers for populations that survive a significant radiation exposure incident. C1 [Yoo, Stephen S.; Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Jorgensen, Timothy J.] Georgetown Univ, Sch Med, Dept Radiat Med, Washington, DC USA. [Kennedy, Ann R.] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Boice, John D., Jr.] Vanderbilt Univ Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med, Div Epidemiol, Nashville, TN USA. [Boice, John D., Jr.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA. [Shapiro, Alla] US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Emergency Coordinat, Silver Spring, MD USA. [Hu, Tom C-C; Moyer, Brian R.; Grace, Marcy B.] BARDA, Dept Hlth & Human Serv, Div CBRN Countermeasures, Off Assistant Secretary Preparedness & Response,O, Washington, DC USA. [Kelloff, Gary J.] NCI, Canc Imaging Program, Div Canc Treatment & Diag, NIH, Bethesda, MD USA. [Fenech, Michael] Commonwealth Sci & Ind Res Org, Adelaide, SA, Australia. RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, 9609 Med Ctr Dr 3W102, Bethesda, MD 20892 USA. FU NCI's Radiation Research Program FX NCI's Radiation Research Program supported this work. The views expressed are those of the authors; no endorsement by NCI or other agencies has been given or inferred. This article has been reviewed by FDA and determined not to be consistent with Agency's views or policies. It reflects only the views and opinions of the author. Authors would like to acknowledge and thank the critical reading and review of the manuscript by Drs Rosemary Roberts and Joanne Holmes, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, USA. NR 172 TC 3 Z9 3 U1 0 U2 16 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0952-4746 EI 1361-6498 J9 J RADIOL PROT JI J. Radiol. Prot. PD JUN PY 2014 VL 34 IS 2 BP R25 EP R52 DI 10.1088/0952-4746/34/2/R25 PG 28 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AJ7US UT WOS:000337904600002 PM 24727460 ER PT J AU Nobert, K AF Nobert, K. TI Animal health: veterinary regenerative medicine SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Meeting Abstract C1 [Nobert, K.] US FDA, Squire Sanders LLP, Washington, DC 20204 USA. [Nobert, K.] Stem Cell Regulatory, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-6254 EI 1932-7005 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD JUN PY 2014 VL 8 SU 1 SI SI MA OP82 BP 83 EP 83 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA AJ4AW UT WOS:000337612600151 ER PT J AU Wang, MO Piard, C Dreher, ML Melchiorri, A Fisher, JP AF Wang, M. O. Piard, C. Dreher, M. L. Melchiorri, A. Fisher, J. P. TI Degradation of 3D printed poly(propylene fumarate) scaffolds SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Meeting Abstract C1 [Wang, M. O.; Melchiorri, A.; Fisher, J. P.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Piard, C.] Paris Tech, Les Arts & Metier ENSAM, Paris, France. [Dreher, M. L.] US FDA, Div Solid & Fluid Mech, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 2 TC 0 Z9 0 U1 4 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-6254 EI 1932-7005 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD JUN PY 2014 VL 8 SU 1 SI SI MA OP95 BP 90 EP 91 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA AJ4AW UT WOS:000337612600164 ER PT J AU Wang, MO Piard, C Dreher, ML Melchiorri, A Fisher, JP AF Wang, M. O. Piard, C. Dreher, M. L. Melchiorri, A. Fisher, J. P. TI Degradation of 3D printed poly(propylene fumarate) scaffolds SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Meeting Abstract C1 [Wang, M. O.; Melchiorri, A.; Fisher, J. P.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Piard, C.] Les Arts & Metier ENSAM, Paris, France. [Dreher, M. L.] US FDA, Div Solid & Fluid Mech, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 2 TC 0 Z9 0 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-6254 EI 1932-7005 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD JUN PY 2014 VL 8 SU 1 SI SI MA PP407 BP 443 EP 443 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA AJ4AW UT WOS:000337612601098 ER PT J AU Jha, RC Zanello, PA Ascher, SM Rajan, S AF Jha, Reena C. Zanello, Paulo A. Ascher, Susan M. Rajan, Sunder TI Diffusion-weighted imaging (DWI) of adenomyosis and fibroids of the uterus SO ABDOMINAL IMAGING LA English DT Article ID URINARY-BLADDER CARCINOMA; UTERINE JUNCTIONAL ZONE; HEPATIC METASTASES; MR; TUMOR; LESIONS; CELLULARITY; LEIOMYOMAS; MYOMETRIUM; SEQUENCES AB Although magnetic resonance imaging is often able to distinguish between adenomyosis and fibroids, occasionally the imaging features of focal adenomyosis and fibroids overlap. Diffusion-weighted imaging (DWI) may provide useful information in differentiating pathologies. Therefore, the purpose of our study was to evaluate differences, if any, in the apparent diffusion coefficient (ADC) values of fibroids and adenomyosis. Patients (n = 50) with uterine fibroids and adenomyosis (n = 43), who underwent pelvic MR imaging including DWI, were included in this IRB approved HIPPA compliant retrospective study. DWI was performed with b factors of 50, 400, and 800 s/mm using a 1.5 T scanner. ADC ROI measurements were placed over a fibroid, an area of adenomyosis, unaffected normal myometrium, skeletal muscle, and urine. Histogram analysis of ADC maps in 20 cases each of adenomyosis and fibroids was evaluated to assess the degree of tissue heterogeneity. The ADC values of adenomyosis and fibroids were compared using Student's t test. The mean and the standard deviation of the ADC values of the control group were as follows: fibroid 0.64 +/- A 0.29, adenomyosis 0.86 +/- A 0.30, myometrium 1.39 +/- A 0.36, and urine 3.01 +/- A 0.2 x 10(-3) mm(2)/s. There was a statistically significant difference among the ADC values of normal myometrium and fibroids (p < 0.0001), normal myometrium and adenomyosis (p < 0.0001), and fibroids and adenomyosis (p < 0.001). Histogram analysis demonstrates less heterogeneity of adenomyosis as compared to fibroids. The present study shows that ADC measurements have the potential to quantitatively differentiate between fibroids and adenomyosis. C1 [Jha, Reena C.; Ascher, Susan M.] Medstar Georgetown Univ Hosp, Dept Radiol, Washington, DC 20007 USA. [Rajan, Sunder] US FDA, Off Sci & Engn Labs, Silver Spring, MD USA. RP Jha, RC (reprint author), Medstar Georgetown Univ Hosp, Dept Radiol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM jhar@gunet.georgetown.edu NR 35 TC 4 Z9 6 U1 3 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD JUN PY 2014 VL 39 IS 3 BP 562 EP 569 DI 10.1007/s00261-014-0095-z PG 8 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA AJ5RA UT WOS:000337742200016 PM 24531353 ER PT J AU Ruan, JQ Yang, MB Fu, P Ye, Y Lin, G AF Ruan, Jianqing Yang, Mengbi Fu, Peter Ye, Yang Lin, Ge TI Metabolic Activation of Pyrrolizidine Alkaloids: Insights into the Structural and Enzymatic Basis SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID DNA CROSS-LINKING; RAT-LIVER; CLIVORINE; SENECIONINE; TOXICITY; TUMORIGENICITY; HEPATOTOXICITY; MICROSOMES; ADDUCTS AB Pyrrolizidine alkaloids (PM) are natural toxins widely distributed in plants. The toxic potencies of different PM vary significantly. PM are mono- or diesters of necine acids with a necine base. On the basis of the necine bases, PM are classified into three types: retronecine-type, otonecine-type, and platynecine-type. Hepatotoxic PM contain an unsaturated necine base. PAs exert hepatotoxicity through metabolic activation by hepatic cytochromes P450s (CYPs) to generate reactive intermediates which form pyrrole protein adducts. These adducts provide a mechanism-based biomarker to assess PA toxicity. In the present study, metabolic activation of 12 PM from three structural types was investigated first in mice to demonstrate significant variations in hepatic metabolic activation of different PM. Subsequently, the structural and enzymatic factors affecting metabolic activation of these PM were further investigated by using human liver microsomes and recombinant human CYPs. Pyrrole protein adducts were detected in the liver and blood of mice and the in vitro systems treated with toxic retronecine-type and otonecine-type PM having unsaturated necine bases but not with a platynecine-type PA containing a saturated necine base. Retronecine-type PM produced more pyrrole protein adducts than otonecine-type PM with similar necine acids, demonstrating that the structure of necine base affected PA toxic potency. Among retronecine-type PM, open-ring diesters generated the highest amount of pyrrole protein adducts, followed by macrocyclic diesters, while monoesters produced the least. Only CYP3A4 and CYP3A5 activated otonecine-type PM, while all 10 CYPs studied showed the ability to activate retronecine-type PM. Moreover, the contribution of major CYPs involved also varied significantly among retronecine-type PM. In conclusion, our findings provide a scientific basis for predicting the toxicities of individual PM in biological systems based on PA structural features and on the pattern of expression and the selectivity of the CYP isoforms present. C1 [Ruan, Jianqing; Yang, Mengbi; Lin, Ge] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. [Ruan, Jianqing; Yang, Mengbi; Ye, Yang; Lin, Ge] Chinese Acad Sci, Joint Res Lab Promoting Globalizat Tradit Chinese, Hong Kong, Hong Kong, Peoples R China. [Ruan, Jianqing; Yang, Mengbi; Ye, Yang; Lin, Ge] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Fu, Peter] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ye, Yang] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res & Nat Prod, Dept Chem, Shanghai 201203, Peoples R China. RP Lin, G (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. EM linge@cuhk.edu.hk FU Research Grant Council of Hong Kong [471013, 469712]; Chinese University of Hong Kong [4054047] FX The present study was supported by Research Grant Council of Hong Kong for GRF Grants (ref. no. 471013 and 469712) and The Chinese University of Hong Kong for the Direct Grant (ref. no. 4054047). NR 39 TC 15 Z9 15 U1 4 U2 36 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X EI 1520-5010 J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUN PY 2014 VL 27 IS 6 BP 1030 EP 1039 DI 10.1021/tx500071q PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA AJ3HQ UT WOS:000337557500013 PM 24836403 ER PT J AU Stine, CB Reimschuessel, R Keltner, Z Nochetto, CB Black, T Olejnik, N Scott, M Bandele, O Nemser, SM Tkachenko, A Evans, ER Crosby, TC Ceric, O Ferguson, M Yakes, BJ Sprando, R AF Stine, Cynthia B. Reimschuessel, Renate Keltner, Zachary Nochetto, Cristina B. Black, Thomas Olejnik, Nicholas Scott, Michael Bandele, Omani Nemser, Sarah M. Tkachenko, Andriy Evans, Eric R. Crosby, Tina C. Ceric, Olgica Ferguson, Martine Yakes, Betsy J. Sprando, Robert TI Reproductive toxicity in rats with crystal nephropathy following high doses of oral melamine or cyanuric acid SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Melamine; Cyanuric acid; Reproductive toxicity; Rats ID CARCINOGENICITY; FETUSES; KIDNEY; FETAL; DAMS; PIGS AB The industrial chemical melamine was used in 2007 and 2008 to raise the apparent protein content in pet feed and watered down milk, respectively. Because humans may be exposed to melamine via several different routes into the human diet as well as deliberate contamination, this study was designed to characterize the effect of high dose melamine or cyanuric acid oral exposure on the pregnant animal and developing fetus, including placental transfer. Clear rectangular crystals formed following a single triazine exposure which is a different morphology from the golden spherulites caused by combined exposure or the calculi formed when melamine combines with endogenous uric acid. Crystal nephropathy, regardless of cause, induces renal failure which in turn has reproductive sequelae. Specifically, melamine alone-treated dams had increased numbers of early and late fetal deaths compared to controls or cyanuric acid-treated dams. As melamine was found in the amniotic fluid, this study confirms transfer of melamine from mammalian mother to fetus and our study provides evidence that cyanuric acid also appears in the amniotic fluid if mothers are exposed to high doses. Published by Elsevier Ltd. C1 [Stine, Cynthia B.; Reimschuessel, Renate; Nochetto, Cristina B.; Nemser, Sarah M.; Tkachenko, Andriy; Evans, Eric R.; Crosby, Tina C.; Ceric, Olgica] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Keltner, Zachary; Black, Thomas; Olejnik, Nicholas; Scott, Michael; Bandele, Omani; Ferguson, Martine; Yakes, Betsy J.; Sprando, Robert] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Yakes, Betsy J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Stine, CB (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM cynthia.stine@fda.hhs.gov; renate.reimschuessel@fda.hhs.gov; zachary.keltner@fda.hhs.gov; cristina.nochetto@fda.hhs.gov; thomas.black@fda.hhs.gov; nicholas.olejnik@fda.hhs.gov; michael.scott@fda.hhs.gov; omari.bandele@fda.hhs.gov; sarah.nemser@fda.hhs.gov; andriy.tkachenko@fda.hhs.gov; eric.evans@fda.hhs.gov; tina.crosby@fda.hhs.gov; olgica.ceric@fda.hhs.gov; martine.ferguson@fda.hhs.gov; betsy.yakes@fda.hhs.gov; robert.sprando@fda.hhs.gov NR 35 TC 11 Z9 11 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2014 VL 68 BP 142 EP 153 DI 10.1016/j.fct.2014.02.029 PG 12 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA AJ4NL UT WOS:000337653000017 PM 24582682 ER PT J AU Liang, Y Woodle, SA Weinstein, M Lee, TK Scott, D Ovanesov, MV AF Liang, Y. Woodle, S. A. Weinstein, M. Lee, T. K. Scott, D. Ovanesov, M., V TI Evaluation of assays for factor XIa to reduce the thrombotic risk of immunoglobulins SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Liang, Y.; Woodle, S. A.; Weinstein, M.; Lee, T. K.; Scott, D.; Ovanesov, M., V] US FDA, Off Blood Res & Review, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUN PY 2014 VL 12 SU 1 SI SI MA FNCS03 BP 46 EP 46 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AJ5BR UT WOS:000337696100121 ER PT J AU Chang, WC Xin, KZ Lee, TK Ovanesov, MV AF Chang, W. C. Xin, K. Z. Lee, T. K. Ovanesov, M., V TI Observation of clot formation and lysis in conjunction with the thrombin generation assay SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Chang, W. C.; Xin, K. Z.; Lee, T. K.; Ovanesov, M., V] US FDA, Off Blood Res & Review, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUN PY 2014 VL 12 SU 1 SI SI MA PHV09 BP 82 EP 82 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AJ5BR UT WOS:000337696100217 ER PT J AU Sharfstein, JM AF Sharfstein, Joshua M. TI On Working for Henry Waxman SO MILBANK QUARTERLY LA English DT Editorial Material C1 [Sharfstein, Joshua M.] Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. [Sharfstein, Joshua M.] US FDA, Rockville, MD 20857 USA. [Sharfstein, Joshua M.] US House Representat, Comm Govt Reform, Washington, DC USA. [Sharfstein, Joshua M.] US Dept HHS, Hlth Informat Technol Policy Comm, Washington, DC USA. RP Sharfstein, JM (reprint author), Maryland Dept Hlth & Mental Hyg, 201 West Preston St,Suite 500, Baltimore, MD 21201 USA. EM joshua.sharfstein@maryland.gov NR 9 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-378X EI 1468-0009 J9 MILBANK Q JI Milbank Q. PD JUN PY 2014 VL 92 IS 2 BP 186 EP 190 DI 10.1111/1468-0009.12050 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AJ2WK UT WOS:000337525000005 PM 24890240 ER PT J AU Song, YS Gera, M Jain, B Koontz, JL AF Song, Yoon S. Gera, Mohit Jain, Bulbul Koontz, John L. TI Evaluation of a Non-destructive High-voltage Technique for the Detection of Pinhole Leaks in Flexible and Semi-rigid Packages for Foods SO PACKAGING TECHNOLOGY AND SCIENCE LA English DT Article DE high voltage; leak detection; packaging; integrity testing ID CONTAMINATION AB This study evaluated the capabilities of a high-voltage technique for the detection of pinhole leaks by using flexible pouches and semi-rigid cups for foods. This evaluation was performed by measuring the discharge voltage when high voltages ranging from 0.25 to 10kV were applied to sample packages. The results showed that package contact surface area, film thickness, food type and electrical conductivity are significant factors affecting the detection of pinhole leaks in flexible pouches by a high-voltage leak detection (HVLD) system within the ranges tested (p<0.05). For plastic cups with plastic-laminated and foil-laminated lids, the headspace inside a cup had the greatest effect followed by dielectric constant of lid films, electrical conductivity of foods and pinhole diameter (p<0.01). In general, the HVLD system can detect pinholes as small as 10 mu m in both plastic-laminated and foil-laminated pouches and lid cups, even at worst-case scenario conditions, including liquid, semi-solid and solid foods with 0.85aw. Because of high voltages applied, however, delamination in foil-laminated films occurred when an applied voltage was greater than 3.5kV, which resulted in increased oxygen permeability. Statistical z-test analysis of results from blind studies showed that the HVLD technique is significantly effective in determining defective pouches and cups with pinhole leaks as small as 10 mu m (p<0.05). Therefore, it can be concluded that the HVLD technique is a promising non-destructive and on-line method to detect pinhole defects, which may be applicable to a wide range of hermetically sealed packages. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Song, Yoon S.; Koontz, John L.] US FDA, OFS, Proc Engn Branch, Bedford Pk, IL 60501 USA. [Gera, Mohit; Jain, Bulbul] IIT, Bedford Pk, IL 60501 USA. RP Song, YS (reprint author), US FDA, OFS, Proc Engn Branch, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM Yoon.Song@fda.hhs.gov NR 23 TC 2 Z9 2 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-3214 EI 1099-1522 J9 PACKAG TECHNOL SCI JI Packag. Technol. Sci. PD JUN PY 2014 VL 27 IS 6 BP 423 EP 436 DI 10.1002/pts.2040 PG 14 WC Engineering, Manufacturing; Food Science & Technology SC Engineering; Food Science & Technology GA AJ3PG UT WOS:000337578500001 ER PT J AU Raebel, MA Haynes, K Woodworth, TS Saylor, G Cavagnaro, E Coughlin, KO Curtis, LH Weiner, MG Archdeacon, P Brown, JS AF Raebel, Marsha A. Haynes, Kevin Woodworth, Tiffany S. Saylor, Gwyn Cavagnaro, Elizabeth Coughlin, Kara O. Curtis, Lesley H. Weiner, Mark G. Archdeacon, Patrick Brown, Jeffrey S. TI Electronic clinical laboratory test results data tables: lessons from Mini-Sentinel SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE distributed data network; laboratory test results; post-marketing evaluation; safety surveillance; administrative database; clinical database; electronic laboratory databases; pharmacoepidemiology ID HEALTH DATA-NETWORKS; LOINC; DESIGN AB PurposeDeveloping electronic clinical data into a common data model posed substantial challenges unique from those encountered with administrative data. We present here the design, implementation, and use of the Mini-Sentinel Distributed Database laboratory results table (LRT). MethodsWe developed the LRT and guided Mini-Sentinel data partners (DPs) in populating it from their source data. Data sources included electronic health records and internal and contracted clinical laboratory systems databases. We employed the Logical Observation Identifiers, Names, and Codes (LOINC (R)) results reporting standards. We evaluated transformed results data using data checks and an iterative, ongoing characterization and harmonization process. ResultsKey LRT variables included test name, subcategory, specimen source, LOINC, patient location, specimen date and time, result unit, and unique person identifier. Selected blood and urine chemistry, hematology, coagulation, and influenza tests were included. Twelve DPs with outpatient test results participated; four also contributed inpatient test results. As of September 2013, the LRT included 385,516,239 laboratory test results; data are refreshed at least quarterly. LOINC availability and use varied across DP. Multiple data quality and content issues were identified and addressed. ConclusionDeveloping the LRT brought together disparate data sources with no common coding structure. Clinical laboratory test results obtained during routine healthcare delivery are neither uniformly coded nor documented in a standardized manner. Applying a systematic approach with data harmonization efforts and ongoing oversight and management is necessary for a clinical laboratory results data table to remain valid and useful. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Raebel, Marsha A.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80237 USA. [Raebel, Marsha A.] Univ Colorado Skaggs, Sch Pharm & Pharmaceut Sci Aurora, Aurora, CO USA. [Haynes, Kevin] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Haynes, Kevin] Univ Penn, Ctr Pharmacoepidemiol Res & Training, Perelman Sch Med, Philadelphia, PA 19104 USA. [Woodworth, Tiffany S.; Cavagnaro, Elizabeth; Coughlin, Kara O.; Brown, Jeffrey S.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Woodworth, Tiffany S.; Cavagnaro, Elizabeth; Coughlin, Kara O.; Brown, Jeffrey S.] Harvard Univ, Sch Med, Boston, MA USA. [Saylor, Gwyn] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA. [Curtis, Lesley H.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Curtis, Lesley H.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Weiner, Mark G.] Temple Univ, Dept Clin Sci, Sch Med, Philadelphia, PA 19122 USA. [Archdeacon, Patrick] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Weiner, Mark G.] Univ Penn, Philadelphia, PA 19104 USA. RP Raebel, MA (reprint author), Kaiser Permanente Colorado, Inst Hlth Res, POB 378066, Denver, CO 80237 USA. EM Marsha.A.Raebel@kp.org NR 22 TC 6 Z9 6 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUN PY 2014 VL 23 IS 6 BP 609 EP 618 DI 10.1002/pds.3580 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AJ2YS UT WOS:000337532000009 PM 24677577 ER PT J AU Mikaelian, I Cameron, M Dalmas, DA Enerson, BE Gonzalez, RJ Guionaud, S Hoffmann, PK King, NMP Lawton, MP Scicchitano, MS Smith, HW Thomas, RA Weaver, JL Zabka, TS AF Mikaelian, Igor Cameron, Mark Dalmas, Deidre A. Enerson, Bradley E. Gonzalez, Raymond J. Guionaud, Silvia Hoffmann, Peter K. King, Nicholas M. P. Lawton, Michael P. Scicchitano, Marshall S. Smith, Holly W. Thomas, Roberta A. Weaver, James L. Zabka, Tanja S. CA Predictive Safety Consortium TI Nonclinical Safety Biomarkers of Drug-induced Vascular Injury: Current Status and Blueprint for the Future SO TOXICOLOGIC PATHOLOGY LA English DT Article DE animal model; arteritis; arteriopathy; nonclinical; vasculopathy; drug development tool; qualification ID SPRAGUE-DAWLEY RATS; SPONTANEOUSLY HYPERTENSIVE-RAT; ANTIBODY-ASSOCIATED VASCULITIS; ENDOTHELIAL MICROPARTICLE LEVELS; PERIADVENTITIAL ADIPOSE-TISSUE; INDUCED PULMONARY-HYPERTENSION; ACUTE CARDIOVASCULAR TOXICITY; FLOW-MEDIATED VASODILATION; ACUTE CORONARY SYNDROMES; PHAGE DISPLAY LIBRARIES AB Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium( PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. C1 [Mikaelian, Igor] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Mikaelian, Igor] Abbvie, Worcester, MA 01605 USA. [Cameron, Mark] MPI Res, Mattawan, MI USA. [Dalmas, Deidre A.; Scicchitano, Marshall S.; Thomas, Roberta A.] GlaxoSmithKline, King Of Prussia, PA USA. [Enerson, Bradley E.; Lawton, Michael P.] Pfizer Inc, Groton, CT 06340 USA. [Gonzalez, Raymond J.] Merck & Co Inc, Merck Res Labs, West Point, PA USA. [Guionaud, Silvia] Hampshire Int Business Pk, Shire, Basingstoke, Hants, England. [Hoffmann, Peter K.] Novartis, E Hanover, NJ USA. [King, Nicholas M. P.] Crit Path Inst, Tucson, AZ USA. [Smith, Holly W.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Weaver, James L.] US FDA, Silver Spring, MD USA. [Zabka, Tanja S.] Genentech Inc, San Francisco, CA 94080 USA. RP Mikaelian, I (reprint author), Abbvie, Worcester, MA 01605 USA. EM igor.mikaelian@abbvie.com NR 260 TC 11 Z9 11 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUN PY 2014 VL 42 IS 4 BP 635 EP 657 DI 10.1177/0192623314525686 PG 23 WC Pathology; Toxicology SC Pathology; Toxicology GA AJ5FZ UT WOS:000337709400002 PM 24777748 ER PT J AU Tobin, GAM Zhang, J Goodwin, D Stewart, S Xu, L Knapton, A Gonzalez, C Bancos, S Zhang, LS Lawton, MP Enerson, BE Weaver, JL AF Tobin, Grainne A. McMahon Zhang, Jun Goodwin, David Stewart, Sharron Xu, Lin Knapton, Alan Gonzalez, Carlos Bancos, Simona Zhang, Leshuai Lawton, Michael P. Enerson, Bradley E. Weaver, James L. TI The Role of eNOS Phosphorylation in Causing Drug-induced Vascular Injury SO TOXICOLOGIC PATHOLOGY LA English DT Article DE animal models; vascular system; drug development; risk identification ID NITRIC-OXIDE SYNTHASE; SPRAGUE-DAWLEY RATS; ENDOTHELIAL GROWTH-FACTOR; INHIBITOR SCH 351591; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNALING PATHWAY; SHEAR-STRESS; NO SYNTHASE; PROTEIN; KINASE AB Previously we found that regulation of eNOS is an important part of the pathogenic process of Drug-induced vascular injury (DIVI) for PDE4i. The aims of the current study were to examine the phosphorylation of eNOS in mesentery versus aorta at known regulatory sites across DIVI-inducing drug classes and to compare changes across species. We found that phosphorylation at S615 in rats was elevated 35-fold 2 hr after the last dose of CI-1044 in mesentery versus 3-fold in aorta. Immunoprecipitation studies revealed that many of the upstream regulators of eNOS activation were associated with eNOS in 1 or more signalosome complexes. Next rats were treated with drugs from 4 other classes known to cause DIVI. Each drug was given alone and in combination with SIN-1 (NO donor) or L-NAME (eNOS inhibitor), and the level of eNOS phosphorylation in mesentery and aorta tissue was correlated with the extent of vascular injury and measured serum nitrite. Drugs or combinations produced altered serum nitrite levels as well as vascular injury score in the mesentery. The results suggested that phosphorylation of S615 may be associated with DIVI activity. Studies with the species-specific A2A adenosine agonist CI-947 in rats versus primates showed a similar pattern. C1 [Tobin, Grainne A. McMahon; Zhang, Jun; Goodwin, David; Stewart, Sharron; Xu, Lin; Knapton, Alan; Gonzalez, Carlos; Bancos, Simona; Zhang, Leshuai; Weaver, James L.] US FDA, Div Appl Regulatory Sci, CDER, Silver Spring, MD 20993 USA. [Lawton, Michael P.; Enerson, Bradley E.] Pfizer Inc, Drug Safety Res & Dev, Groton, CT 06340 USA. [Zhang, Leshuai] Kansas State Univ, Coll Vet Med, Dept Anat & Physiol, Manhattan, KS 66506 USA. RP Weaver, JL (reprint author), US FDA, Div Drug Safety Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM james.weaver@fda.hhs.gov RI Zhang, Leshuai/C-8077-2012 FU U.S. FDA; Pfizer Inc.; Oak Ridge Institute for Science and Education (ORISE) Research Participation Program at the Center for Drug Evaluation and Research FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a Cooperative Research and Development Agreement between the U.S. FDA and Pfizer Inc. This project was supported in part by an appointment to the Oak Ridge Institute for Science and Education (ORISE) Research Participation Program at the Center for Drug Evaluation and Research administered by the ORISE through an agreement between the U.S. Department of Energy and Center for Drug Evaluation and Research (CDER). NR 39 TC 7 Z9 7 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUN PY 2014 VL 42 IS 4 BP 709 EP 724 DI 10.1177/0192623314522885 PG 16 WC Pathology; Toxicology SC Pathology; Toxicology GA AJ5FZ UT WOS:000337709400007 PM 24705881 ER PT J AU Kim, CS Ross, IA Sapienza, PP Hanes, DE Johnson, W Hutter, JC AF Kim, Chung S. Ross, Ivan A. Sapienza, Philip P. Hanes, Darcy E. Johnson, Widmark Hutter, Joseph C. TI Distribution and pharmacokinetics of double-radiolabeled endotoxin in the rat brain and peripheral organs SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE Endotoxin; distribution; pharmacokinetics; infection ID CELL-WALL COMPONENTS; SEPTIC SHOCK; REACTIVE OXYGEN; BINDING-PROTEIN; GUINEA-PIGS; LPS; INACTIVATION; APOPTOSIS; DAMAGE; SERUM AB The endotoxin, lipopolysaccharide (LPS), of Salmonella typhimurium was biosynthetically labeled with H-3 and C-14 incorporated into the fatty acyl chains and glucosamine residues, respectively. The radio-labeled LPS was isolated from the bacteria and then injected into Sprague-Dawley rats. The distribution of C-14 and H-3-LPS in plasma and other organs was determined following intraperitoneal (IP) doses of C-14 and H-3-LPS (200 mu g/kg). Plasma concentrations of both fatty acyl chains and glucosamine residues were biphasic, with a relatively rapid decay followed by a slow decline for 48 h. Similar biphasic results were found in the peripheral organs (kidney and heart) and brain barrier tissues (meninges and choroid plexus). In other brain tissues (brain stem, caudate nucleus, hypothalamus, frontal cortex, cerebellum and hippocampus), the glucosamine residue was biphasic, whereas the fatty acyl chains showed accumulation. Highest concentrations of LPS were found in the plasma, spleen and the liver. In addition, in the liver, sustained elevations of C-14-glucosamine and 3 H-fatty acyl chains were observed. This indicates LPS accumulation in the liver. By contrast, the spleen showed biphasic decay of glucosamine residues and accumulation of fatty acyl chains. In the brain barrier tissues, peak LPS concentrations were significantly reduced (about 70%) and were further reduced (about 95%) in other brain tissues. The high elevation of LPS in the spleen is considered indicative of an immune response. Our findings highlight the potential significant role of lipid A as shown with the sustained elevation of H-3-fatty acyl chains in the brain. C1 [Kim, Chung S.; Ross, Ivan A.; Sapienza, Philip P.; Hanes, Darcy E.; Johnson, Widmark] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Hutter, Joseph C.] Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD USA. RP Kim, CS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM chung.kim@fda.hhs.gov NR 36 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 EI 1477-0393 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUN PY 2014 VL 30 IS 5 BP 432 EP 441 DI 10.1177/0748233712458139 PG 10 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA AJ3PM UT WOS:000337579200006 PM 22933553 ER PT J AU Hutter, JC Kim, CS AF Hutter, Joseph C. Kim, Chung S. TI Physiological-based pharmacokinetic modeling of endotoxin in the rat SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE Endotoxin; distribution; pharmacokinetic model ID 2,4-DICHLOROPHENOXYACETIC ACID DOSIMETRY; RABBIT BRAIN; SEPTIC SHOCK; TISSUE; TRANSPORT; EXPOSURE; HUMANS; INVIVO AB We have previously measured the distribution and pharmacokinetics of biosynthetically radiolabeled endotoxin of Salmonella typhimurium following intraperitoneal (IP) dosing (200 mu g/kg) in Sprague-Dawley rats. In our experiments, the fatty acid residues were labeled with H-3 and the glucosamine residues were labeled with C-14. To predict the dynamics of endotoxin exposure, we developed a physiological-based pharmacokinetic model using our measured distribution results. The model was validated with published low-dose (30 mu g/kg) IP exposure results in rats. Endotoxin pharmacokinetics depended on dose and route. At high IP doses, absorption was followed by biphasic decay over 48 h in plasma. There were tissue accumulations of the fatty acid and glucosamine residues in various target organs, including the brain. We also found that the glucosamine and fatty acid components separated in vivo about 3 h after IP injection. At the lower IP dose, a smaller fraction of the dose was distributed to the tissues, with most of the dose remaining in the blood. Each component had its own dynamic behavior and target tissue distribution in the rat. The fatty acid components tended to remain in the brain stem, caudate nucleus, cerebellum, frontal cortex, hippocampus, and hypothalamus. Other organs (spleen, kidney, meninges, and choroid plexus) had similar biphasic distribution. The liver had the unique accumulation of both glucosamine and fatty acid residues. C1 [Hutter, Joseph C.] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Kim, Chung S.] Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD USA. RP Hutter, JC (reprint author), US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM joseph.hutter@fda.hhs.gov NR 30 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 EI 1477-0393 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUN PY 2014 VL 30 IS 5 BP 442 EP 453 DI 10.1177/0748233712458140 PG 12 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA AJ3PM UT WOS:000337579200007 PM 22933552 ER PT J AU Bosch-Marce, M Seetharaman, S Kurtz, J Mohan, KVK Wagner, SJ Atreya, CD AF Bosch-Marce, Marta Seetharaman, Shalini Kurtz, James Mohan, Ketha V. K. Wagner, Stephen J. Atreya, Chintamani D. TI Leukoreduced whole blood-derived platelets treated with antimicrobial peptides maintain in vitro properties during storage SO TRANSFUSION LA English DT Article ID SIMULATED SHIPPING CONDITIONS; COMBINED IMMUNODEFICIENT MICE; APHERESIS PLATELETS; 7-DAY STORAGE; AGITATION; PERIODS; VIVO; MECHANISMS; SURVIVAL; PLASMA AB Background Bacterial sepsis is still a complication in patients transfused with stored platelets (PLTs). We have recently demonstrated that selected antimicrobial peptides (AMPs) have bactericidal activity in bacteria-spiked PLTs. In a subsequent preclinical study, we have also shown that these AMPs do not elicit antibody response in rabbits and treatment of PLTs before transfusion does not affect their in vivo recovery and survival in severe combined immunodeficient mice. Here we have selected two such AMPs, Arg-Trp (RW) repeats of tri- and tetra-peptides (RW3 and RW4) in combination (i.e., cocktail), and evaluated their effect on the in vitro properties of PLTs. Study Design and Methods Leukoreduced ABO- and D-identical whole blood-derived PLT concentrates were pooled and divided into two 60-mL aliquots in CLX storage bags. On Day 0, one bag received a peptide cocktail of RW3plusRW4 at 0.01mmol/L final concentration (test) and the other bag received only phosphate-buffered saline (PBS), the AMP solvent (control). The treated PLTs were stored for 7 days at 20 to 24 degrees C. Samples were collected on Days 1, 5, and 7 to evaluate the in vitro properties of PLTs with standard assays. Results In vitro properties of the RW3plusRW4 cocktail-treated PLTs were similar to those incubated with PBS only. There were no significant differences between the control and test PLTs during the 7-day storage. Conclusion Leukoreduced whole blood-derived PLTs treated with a mixture of RW3 and RW4 peptides maintain their in vitro properties during 7 days of storage. C1 [Bosch-Marce, Marta; Mohan, Ketha V. K.; Atreya, Chintamani D.] US FDA, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Sect Cell Biol, Bethesda, MD 20014 USA. [Seetharaman, Shalini; Kurtz, James; Wagner, Stephen J.] Amer Red Cross, Blood Components Dept, Rockville, MD USA. RP Atreya, CD (reprint author), Bldg 29A,Room 2C-11,NIH Campus, Bethesda, MD 20892 USA. EM chintamani.atreya@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER) FX MBM is the recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intraagency agreement between the US Department of Energy and the US Food and Drug Administration. The authors thank Ms Sandhya Kulkarni for her help with timely procurement of materials used in this work. NR 32 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD JUN PY 2014 VL 54 IS 6 BP 1604 EP 1609 DI 10.1111/trf.12534 PG 6 WC Hematology SC Hematology GA AJ3TU UT WOS:000337591200024 PM 24410697 ER PT J AU Varadkar, P Despres, D Kraman, M Lozier, J Phadke, A Nagaraju, K Mccright, B AF Varadkar, Prajakta Despres, Daryl Kraman, Matthew Lozier, Julie Phadke, Aditi Nagaraju, Kanneboyina Mccright, Brent TI The protein phosphatase 2A B56 regulatory subunit is required for heart development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE protein phosphatase 2A regulatory B subunit; PP2A; PR61; ventricular septal defect; mouse heart development; cardiomyocyte ID SMOOTH-MUSCLE ACTIN; A-SUBUNIT; PP2A; MICE; EXPRESSION; PHOSPHORYLATION; DIFFERENTIATION; IDENTIFICATION; ALPHA; LOCALIZATION AB Background: Protein Phosphatase 2A (PP2A) function is controlled by regulatory subunits that modulate the activity of the catalytic subunit and direct the PP2A complex to specific intracellular locations. To study PP2A's role in signal transduction pathways that control growth and differentiation in vivo, a transgenic mouse lacking the B56 regulatory subunit of PP2A was made. Results: Lack of PP2A activity specific to the PP2A-B56 holoenzyme, resulted in the formation of an incomplete ventricular septum and a decrease in the number of ventricular cardiomyocytes. During cardiac development, B56 is expressed in the nucleus of -actinin-positive cardiomyocytes that contain Z-bands. The pattern of B56 expression correlated with the cardiomyocyte apoptosis we observed in B56-deficient mice during mid to late gestation. In addition to the cardiac phenotypes, mice lacking B56 have a decrease in locomotive coordination and gripping strength, indicating that B56 has a role in controlling PP2A activity required for efficient neuromuscular function. Conclusions: PP2A-B56 activity is required for efficient cardiomyocyte maturation and survival. The PP2A B56 regulatory subunit controls PP2A substrate specificity in vivo in a manner that cannot be fully compensated for by other B56 subunits. Developmental Dynamics 243:778-790, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Varadkar, Prajakta; Lozier, Julie; Mccright, Brent] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Despres, Daryl] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. [Kraman, Matthew] Univ Cambridge, Cambridge Res Inst, Cambridge, England. [Phadke, Aditi; Nagaraju, Kanneboyina] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Mccright, B (reprint author), 29 Lincoln Dr,Bldg 29B,Room 2NN08, Bethesda, MD 20892 USA. EM brenton.mccright@fda.hhs.gov FU US Department of Defense [W81XWH-09-1-0599] FX The preclinical phenotyping facility at CNMC is supported by a grant from US Department of Defense grant no. W81XWH-09-1-0599 to Dr. Nagaraju. NR 31 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 2014 VL 243 IS 6 BP 778 EP 790 DI 10.1002/dvdy.24111 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA AJ3SI UT WOS:000337587200004 PM 24425002 ER PT J AU Gu, Q Sivanandam, TM AF Gu, Qiang Sivanandam, Thamil Mani TI Optimizing Scan Parameters for Antibody Microarray Experiments: Accelerating Robust Systems Diagnostics for Life Sciences SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID PROTEIN; CALIBRATION; INTENSITIES; DISCOVERY; ARRAYS AB Microarray experiments are a centerpiece of postgenomics life sciences and the current efforts to develop systems diagnostics for personalized medicine. The majority of antibody microarray experiments are fluorescence-based, which utilizes a scanner to convert target signals into image files for subsequent quantification. Certain scan parameters such as the laser power and photomultiplier tube gain (PMT) can influence the readout of fluorescent intensities and thus may affect data quantitation. To date, however, there is no consensus of how to determine the optimal settings of microarray scanners. Here we show that different settings of the laser power and PMT not only affect the signal intensities but also the accuracy of antibody microarray experiments. More importantly, we demonstrate an experimental approach using two fluorescent dyes to determine optimal settings of scan parameters for microarray experiments. These measures provide added quality control of microarray experiments, and thus help to improve the accuracy of quantitative outcome in microarray experiments in the above contexts. C1 [Gu, Qiang; Sivanandam, Thamil Mani] Wake Forest Univ, Bowman Gray Sch Med, Dept Neurobiol & Anat, Winston Salem, NC USA. [Gu, Qiang] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gu, Q (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. EM qiang.gu@fda.hhs.gov FU Mr. and Mrs. Tab Williams Jr. and Family Neuroscience Research and Program Development Endowment FX This work was supported by Mr. and Mrs. Tab Williams Jr. and Family Neuroscience Research and Program Development Endowment. We thank Bryan Lamoreau for assistance in data analyses. The views expressed here are those of the authors and not necessarily those of the U.S. Food and Drug Administration. NR 16 TC 1 Z9 1 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 EI 1557-8100 J9 OMICS JI OMICS PD JUN PY 2014 VL 18 IS 6 BP 385 EP 398 DI 10.1089/omi.2013.0095 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AI9CH UT WOS:000337224900005 PM 24754828 ER PT J AU Husain, SR Ohya, Y Toguchida, J Puri, RK AF Husain, Syed R. Ohya, Yoshikazu Toguchida, Junya Puri, Raj K. TI Current Status of Multipotent Mesenchymal Stromal Cells SO TISSUE ENGINEERING PART B-REVIEWS LA English DT Editorial Material C1 [Husain, Syed R.; Puri, Raj K.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Ohya, Yoshikazu] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Kashiwa, Chiba, Japan. [Toguchida, Junya] Kyoto Univ, Inst Frontier Med Sci, Dept Tissue Regenerat, Kyoto, Japan. [Toguchida, Junya] Kyoto Univ, Ctr iPS Cell Res & Applicat, Dept Cell Growth & Differentiat, Kyoto, Japan. RP Husain, SR (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, HFM 735,NIH Bldg 29B,29 Lincoln Dr,MSC4555, Bethesda, MD 20892 USA. EM syed.husain@fda.hhs.gov NR 2 TC 2 Z9 2 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3368 EI 1937-3376 J9 TISSUE ENG PART B-RE JI Tissue Eng. Part B-Rev. PD JUN PY 2014 VL 20 IS 3 BP 189 EP 189 DI 10.1089/ten.teb.2014.0105 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AI9JU UT WOS:000337249700001 PM 24568643 ER PT J AU Kowey, PR Roberts, WC AF Kowey, Peter Russell Roberts, William Clifford TI PETER RUSSELL KOWEY, MD: a conversation with the editor SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 [Kowey, Peter Russell] Med Coll Penn & Hahnemann Univ, Coronary Care Unit, Philadelphia, PA 19129 USA. [Kowey, Peter Russell] Med Coll Penn & Hahnemann Univ, Cardiac Arrhythmia Serv, Philadelphia, PA USA. [Kowey, Peter Russell] Mainline Hlth Syst, Div Cardiovasc Dis, Bryn Mawr, PA USA. [Kowey, Peter Russell] Lankenau Hosp, Wynnewood, PA USA. [Kowey, Peter Russell] Paoli Mem Hosp, Paoli, PA USA. [Kowey, Peter Russell] Thomas Jefferson Univ Philadelphia, Jefferson Med Coll, Philadelphia, PA USA. [Kowey, Peter Russell] Drexel Univ, Coll Med, MCP Hahnemann, Philadelphia, PA USA. [Kowey, Peter Russell] Heart Ctr Lankenau, Bryn Mawr, PA USA. [Kowey, Peter Russell] Fed Drug Adm, Silver Spring, MD USA. RP Kowey, PR (reprint author), Med Coll Penn & Hahnemann Univ, Coronary Care Unit, Philadelphia, PA 19129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2014 VL 113 IS 11 BP 1917 EP 1931 DI 10.1016/j.amjcard.2014.03.025 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI5YT UT WOS:000336947600023 PM 24837274 ER PT J AU Moro, PL Museru, OI Niu, M Lewis, P Broder, K AF Moro, Pedro L. Museru, Oidda I. Niu, Manette Lewis, Paige Broder, Karen TI Reports to the Vaccine Adverse Event Reporting System after hepatitis A and hepatitis AB vaccines in pregnant women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE hepatitis A hepatitis B combined vaccine; hepatitis A vaccine; pregnancy; surveillance; vaccine safety ID B-VACCINE; SAFETY; VAERS; IMMUNIZATION; SURVEILLANCE AB OBJECTIVE: To characterize adverse events (AEs) after hepatitis A vaccines (Hep A) and hepatitis A and hepatitis B combination vaccine (Hep AB) in pregnant women reported to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. STUDY DESIGN: We searched VAERS for AEs reports in pregnant women who received Hep A or Hep AB from Jan. 1, 1996-April 5, 2013. Clinicians reviewed all reports and available medical records. RESULTS: VAERS received 139 reports of AEs in pregnant women; 7 (5.0%) were serious; no maternal or infant deaths were identified. Sixty-five (46.8%) did not describe any AEs. For those women whose gestational age was available, most were vaccinated during the first trimester, 50/60 (83.3%) for Hep A and 18/21 (85.7%) for Hep AB. The most common pregnancy-specific outcomes following Hep A or Hep AB vaccinations were spontaneous abortion in 15 (10.8%) reports, elective termination in 10 (7.2%), and preterm delivery in 7 (5.0%) reports. The most common nonpregnancy specific outcome was urinary tract infection and nausea/vomiting with 3 (2.2%) reports each. One case of amelia of the lower extremities was reported in an infant following maternal Hep A immunization. CONCLUSION: This review of VAERS reports did not identify any concerning pattern of AEs in pregnant women or their infants following maternal Hep A or Hep AB immunizations during pregnancy. C1 [Moro, Pedro L.; Museru, Oidda I.; Lewis, Paige; Broder, Karen] Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Niu, Manette] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Moro, PL (reprint author), Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. NR 26 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2014 VL 210 IS 6 AR 561.e1 DI 10.1016/j.ajog.2013.12.036 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI1CS UT WOS:000336588000022 PM 24378675 ER PT J AU Yang, BW Cui, Y Shi, C Wang, JQ Xia, XD Xi, ML Wang, X Meng, JH Alali, WQ Walls, I Doyle, MP AF Yang, Baowei Cui, Yue Shi, Chao Wang, Jiaqi Xia, Xiaodong Xi, Meili Wang, Xin Meng, Jianghong Alali, Walid Q. Walls, Isabel Doyle, Michael P. TI Counts, Serotypes, and Antimicrobial Resistance of Salmonella Isolates on Retail Raw Poultry in the People's Republic of China SO JOURNAL OF FOOD PROTECTION LA English DT Article ID UNITED-STATES; CAMPYLOBACTER SPP.; CHICKEN CARCASSES; ORGANIC CHICKENS; PREVALENCE; SEROVARS; ENTERITIDIS; SURVEILLANCE; INFECTIONS; OUTBREAK AB The objective of this study was to determine Salmonella counts, serotypes, and antimicrobial resistance profiles in retail raw chicken meat in the People's Republic of China. Salmonella counts were determined according to the most-probable-number (MPN) method for 300 whole chicken carcasses. These samples were collected from large, small, and wet (open) markets in Guangdong, Shaanxi, and Sichuan provinces. Salmonella isolates were serotyped and tested for antimicrobial susceptibility. Of the 300 chicken carcasses, 43.3% were positive for Salmonella, with an overall mean of 1.7 log MPN per carcass (95% confidence interval, 1.6 to 1.8 log MPN per carcass). No significant differences (P > 0.05) were detected for storage temperature (i.e., chilled, frozen, or ambient), market type (large, small, or wet), province, or location (capital or noncapital city). Seventy-eight serotypes were identified among the 1,094 Salmonella isolates. The top five most common Salmonella serotypes on raw chicken carcasses were Enteritidis (19.2%), Indiana (15.2%), Typhimurium (14.6%), Agona (7.1%), and Thompson (6.6%). Salmonella isolates (n = 779) were most frequently resistant to sulfisoxazole (74.1%) and tetracycline (71.1%) and least resistant to ceftriaxone (22.5%) and cefoxitin (19%). Only 4% of the isolates were susceptible to all 15 antimicrobial agents, 45% were resistant to 1 to 5 agents, 29% were resistant to 6 to 10 agents, and 22% were resistant to 11 to 15 agents. Our findings revealed that Salmonella contamination was common in retail raw poultry in China, and the counts on contaminated carcasses were mostly low. Salmonella isolates were diverse in their serotype distribution and antimicrobial susceptibility profiles, with mote than half of the isolates resistant to more than five antimicrobial agents. These data may be used in risk assessment models to reduce the transmission of Salmonella via chicken meat to humans in China. C1 [Yang, Baowei; Cui, Yue; Shi, Chao; Wang, Jiaqi; Xia, Xiaodong; Xi, Meili; Wang, Xin; Meng, Jianghong] Northwest A&F Univ, Coll Food Sci, Yangling 712100, Peoples R China. [Cui, Yue; Alali, Walid Q.; Doyle, Michael P.] Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Walls, Isabel] USDA, Natl Inst Food & Agr, Washington, DC 20250 USA. RP Alali, WQ (reprint author), Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. EM walali@uga.edu OI Walls, Isabel/0000-0002-9643-8845 FU project "Enumeration and Characterization of Salmonella from Retail Raw Chicken in China" of the University of Georgia; Northwest AF University; World Health Organization Global Foodborne Infections Network FX This research was supported by the project "Enumeration and Characterization of Salmonella from Retail Raw Chicken in China" of the University of Georgia and Northwest A&F University in collaboration with the World Health Organization Global Foodborne Infections Network. We are grateful to Dr. Ming Liao (South China Agricultural University) and Dr. Xiaonong Yang (Southwest University for Nationalities, Chengdu, Sichuan, Peoples's Republic of China) for sample collection and laboratory work. NR 37 TC 9 Z9 10 U1 3 U2 26 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2014 VL 77 IS 6 BP 894 EP 902 DI 10.4315/0362-028X.JFP-13-439 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA AI4YA UT WOS:000336871300004 PM 24853510 ER PT J AU Epperson, F Oblak, A Murrell, J Richardson, R Dupree, B Piccardo, P Gambetti, P Ghetti, B AF Epperson, Francine Oblak, Adrian Murrell, Jill Richardson, Rose Dupree, Brenda Piccardo, Pedro Gambetti, Pierluigi Ghetti, Bernardino TI Creutzfeldt-Jakob Disease: Review of the Past Twenty Three Year Experience SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [Epperson, Francine; Oblak, Adrian; Murrell, Jill; Richardson, Rose; Dupree, Brenda; Ghetti, Bernardino] IU Sch Med, Dept Pathol & Lab Med, Indianpolis, India. [Piccardo, Pedro] US FDA, Rockville, MD 20857 USA. [Gambetti, Pierluigi] Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 150 BP 625 EP 625 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100160 ER PT J AU Ma, HL Galvin, TA Glasner, DR Shaheduzzaman, S Khan, AS AF Ma, Hailun Galvin, Teresa A. Glasner, Dustin R. Shaheduzzaman, Syed Khan, Arifa S. TI Identification of a Novel Rhabdovirus in Spodoptera frugiperda Cell Lines SO JOURNAL OF VIROLOGY LA English DT Article ID STRAND RNA VIRUSES; ENDOGENOUS RETROVIRUS; MAXIMUM-LIKELIHOOD; POLYMERASE GENE; SEQUENCE; DROSOPHILA; PROTEIN; CYTORHABDOVIRUS; MULTIPLE; LETTUCE AB The Sf9 cell line, derived from Spodoptera frugiperda, is used as a cell substrate for biological products, and no viruses have been reported in this cell line after extensive testing. We used degenerate PCR assays and massively parallel sequencing (MPS) to identify a novel RNA virus belonging to the order Mononegavirales in Sf9 cells. Sequence analysis of the assembled virus genome showed the presence of five open reading frames (ORFs) corresponding to the genes for the N, P, M, G, and L proteins in other rhabdoviruses and an unknown ORF of 111 amino acids located between the G-and L-protein genes. BLAST searches indicated that the S. frugiperda rhabdovirus (Sf-rhabdovirus) was related in a limited region of the L-protein gene to Taastrup virus, a newly discovered member of the Mononegavirales from a leafhopper (Hemiptera), and also to plant rhabdoviruses, particularly in the genus Cytorhabdovirus. Phylogenetic analysis of sequences in the L-protein gene indicated that Sf-rhabdovirus is a novel virus that branched with Taastrup virus. Rhabdovirus morphology was confirmed by transmission electron microscopy of filtered supernatant samples from Sf9 cells. Infectivity studies indicated potential transient infection by Sf-rhabdovirus in other insect cell lines, but there was no evidence of entry or virus replication in human cell lines. Sf-rhabdovirus sequences were also found in the Sf21 parental cell line of Sf9 cells but not in other insect cell lines, such as BT1-TN-B-5(1-4) (Tn(5); High Five) cells and Schneider's Drosophila line 2 [D. Mel.(2); SL2] cells, indicating a species-specific infection. The results indicate that conventional methods may be complemented by state-of-the-art technologies with extensive bioinformatics analysis for identification of novel viruses. C1 [Ma, Hailun; Galvin, Teresa A.; Glasner, Dustin R.; Shaheduzzaman, Syed; Khan, Arifa S.] US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Khan, AS (reprint author), US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM arifa.khan@fda.hhs.gov FU FDA's Medical Countermeasures Initiative FX The project was funded by FDA's Medical Countermeasures Initiative. NR 42 TC 13 Z9 14 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2014 VL 88 IS 12 BP 6576 EP 6585 DI 10.1128/JVI.00780-14 PG 10 WC Virology SC Virology GA AI5HF UT WOS:000336895600006 PM 24672045 ER PT J AU Camp, KM Parisi, MA Acosta, PB Berry, GT Bilder, DA Blau, N Bodamer, OA Brosco, JP Brown, CS Burlina, AB Burton, BK Chang, CS Coates, PM Cunningham, AC Dobrowolski, SF Ferguson, JH Franklin, TD Frazier, DM Grange, DK Greene, CL Groft, SC Harding, CO Howell, RR Huntington, KL Hyatt-Knorr, HD Jevaji, IP Levy, HL Lichter-Konecki, U Lindegren, ML Lloyd-Puryear, MA Matalon, K MacDonald, A McPheeters, ML Mitchell, JJ Mofidi, S Moseley, KD Mueller, CM Mulberg, AE Nerurkar, LS Ogata, BN Pariser, AR Prasad, S Pridjian, G Rasmussen, SA Reddy, UM Rohr, FJ Singh, RH Sirrs, SM Stremer, SE Tagle, DA Thompson, SM Urv, TK Utz, JR van Spronsen, F Vockley, J Waisbren, SE Weglicki, LS White, DA Whitley, CB Wilfond, BS Yannicelli, S Young, JM AF Camp, Kathryn M. Parisi, Melissa A. Acosta, Phyllis B. Berry, Gerard. T. Bilder, Deborah A. Blau, Nenad Bodamer, Olaf A. Brosco, Jeffrey P. Brown, Christine S. Burlina, Alberto B. Burton, Barbara K. Chang, Christine S. Coates, Paul M. Cunningham, Amy C. Dobrowolski, Steven F. Ferguson, John H. Franklin, Thomas D. Frazier, Dianne M. Grange, Dorothy K. Greene, Carol L. Groft, Stephen C. Harding, Cary O. Howell, R. Rodney Huntington, Kathleen L. Hyatt-Knorr, Henrietta D. Jevaji, Indira P. Levy, Harvey L. Lichter-Konecki, Uta Lindegren, Mary Lou Lloyd-Puryear, Michele A. Matalon, Kimberlee MacDonald, Anita McPheeters, Melissa L. Mitchell, John J. Mofidi, Shideh Moseley, Kathryn D. Mueller, Christine M. Mulberg, Andrew E. Nerurkar, Lata S. Ogata, Beth N. Pariser, Anne R. Prasad, Suyash Pridjian, Gabriella Rasmussen, Sonja A. Reddy, Uma M. Rohr, Frances J. Singh, Rani H. Sirrs, Sandra M. Stremer, Stephanie E. Tagle, Danilo A. Thompson, Susan M. Urv, Tiina K. Utz, Jeanine R. van Spronsen, Francjan Vockley, Jerry Waisbren, Susan E. Weglicki, Linda S. White, Desiree A. Whitley, Chester B. Wilfond, Benjamin S. Yannicelli, Steven Young, Justin M. TI Phenylketonuria Scientific Review Conference: State of the science and future research needs SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Phenylketonuria; Sapropterin; Hyperphenylalaninemia; Maternal PIN; Large neutral amino acids; Glycomacropeptide ID PHENYLALANINE-HYDROXYLASE DEFICIENCY; NEUTRAL AMINO-ACIDS; DIHYDROPTERIDINE REDUCTASE DEFICIENCY; CONTINUOUSLY TREATED PHENYLKETONURIA; TETRAHYDROBIOPTERIN LOADING TEST; GENOTYPE-PHENOTYPE CORRELATIONS; THERAPEUTIC LIVER REPOPULATION; MATERNAL BLOOD PHENYLALANINE; ENZYME REPLACEMENT THERAPY; TANDEM MASS-SPECTROMETRY AB New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 Rtnol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 [tmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism. C1 [Camp, Kathryn M.; Coates, Paul M.; Lloyd-Puryear, Michele A.] NIH, Off Dietary Supplements, Bethesda, MD 20982 USA. [Parisi, Melissa A.; Reddy, Uma M.; Urv, Tiina K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Acosta, Phyllis B.; Singh, Rani H.] Emory Univ, Atlanta, GA 30033 USA. [Berry, Gerard. T.; Levy, Harvey L.; Waisbren, Susan E.] Harvard Univ, Boston Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Bilder, Deborah A.] Univ Utah, Dept Psychiat, Salt Lake City, UT 84108 USA. [Blau, Nenad] Univ Childrens Hosp, Heidelberg, Germany. [Blau, Nenad] Univ Childrens Hosp, Zurich, Switzerland. [Bodamer, Olaf A.; Howell, R. Rodney] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Brosco, Jeffrey P.] Univ Miami, Mailman Ctr Child Dev, Miami, FL 33101 USA. [Brown, Christine S.; Franklin, Thomas D.] Natl PKU Alliance, Encinitas, CA USA. [Burlina, Alberto B.] Univ Hosp, I-35128 Padua, Italy. [Burton, Barbara K.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Chang, Christine S.] Agcy Healthcare Res & Qual, Rockville, MD 20850 USA. [Cunningham, Amy C.; Pridjian, Gabriella] Tulane Univ, Sch Med, Hayward Genet Ctr, New Orleans, LA 70112 USA. [Dobrowolski, Steven F.; Vockley, Jerry] Univ Pittsburgh, Pittsburgh, PA 15224 USA. [Ferguson, John H.; Groft, Stephen C.; Hyatt-Knorr, Henrietta D.; Nerurkar, Lata S.] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20982 USA. [Frazier, Dianne M.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Grange, Dorothy K.] Washington Univ, St Louis Childrens Hosp, Sch Med, St Louis, MO 63110 USA. [Greene, Carol L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Harding, Cary O.; Huntington, Kathleen L.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Jevaji, Indira P.] NIH, Off Res Womens Hlth, Bethesda, MD 20817 USA. [Lichter-Konecki, Uta] George Washington Univ, Childrens Natl Med Ctr, Washington, DC 20010 USA. [Lindegren, Mary Lou] Vanderbilt Univ, Sch Med, Nashville, TN 37203 USA. [Matalon, Kimberlee] Univ Houston, Houston, TX 77204 USA. [MacDonald, Anita] Birmingham Childrens Hosp, Birmingham B4 6NH, W Midlands, England. [McPheeters, Melissa L.] Inst Med & Publ Hlth, Vanderbilt Evidence Based Practice Ctr, Nashville, TN 37203 USA. [Mitchell, John J.] McGill Univ, Ctr Hlth, Montreal, PQ H3H 1P3, Canada. [Mofidi, Shideh] Maria Fareri Childrens Hosp, Westchester Med Ctr, Valhalla, NY 10595 USA. [Moseley, Kathryn D.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Mueller, Christine M.] US FDA, Off Orphan Prod Dev, Silver Spring, MD 20993 USA. [Mulberg, Andrew E.; Pariser, Anne R.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Ogata, Beth N.] Univ Washington, Seattle, WA 98195 USA. [Prasad, Suyash] BioMarin Pharmaceut Inc, San Rafael, CA 94901 USA. [Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Rohr, Frances J.] Boston Childrens Hosp, Boston, MA 02115 USA. [Sirrs, Sandra M.] Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. [Burlina, Alberto B.] PKU & Allied Disorders Wisconsin, Madison, WI 53705 USA. [Tagle, Danilo A.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Thompson, Susan M.] Childrens Hosp Westrnead, Sydney, NSW 2145, Australia. [Utz, Jeanine R.; Whitley, Chester B.] Univ Minnesota, Minneapolis, MN 55455 USA. [van Spronsen, Francjan] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, NL-9700 AB Groningen, Netherlands. [Weglicki, Linda S.] NINR, NIH, Bethesda, MD 20892 USA. [White, Desiree A.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Wilfond, Benjamin S.] Univ Washington, Seattle Childrens Res Inst, Sch Med, Seattle, WA 98101 USA. [Yannicelli, Steven] Nutricia North Amer, Rockville, MD 20850 USA. [Young, Justin M.] Young Face Facial Plast & Reconstruct Surg, Cumming, GA 30041 USA. RP Camp, KM (reprint author), 6100 Execut Blvd, Rockville, MD 20892 USA. EM campkm@od.nih.gov; parisima@mail.nih.gov; pja1933@gmail.com; gerard.berry@childrens.harvard.edu; deborah.bilder@hsc.utah.edu; nenad.blau@med.uni-heidelberg.de; obodamer@med.miami.edu; jbrosco@med.miami.edu; christine.brown@npkua.org; alberto.burlina@unipd.it; bburton@luriechildrens.org; christine.chang@ahrq.hhs.gov; coatesp@od.nih.gov; acunnin@tulane.edu; dobrowolskis@upmc.edu; jferg@helix.nih.gov; tom.franklin@npkua.org; dianne_frazier@med.unc.edu; grange_d@kids.wustl.edu; cgreene@peds.umaryland.edu; stephen.groft@nih.gov; hardingc@ohsu.edu; rhowell@miami.edu; huntingt@ohsu.edu; henrietta.hyatt-knorr@nih.gov; indira.jevaji@cms.hhs.gov; harvey.levy@childrens.harvard.edu; ulichter@cnmc.org; marylou.lindegren@vanderbilt.edu; lloydpuryearma@od.nih.gov; kmatalon@uh.edu; anita.macdonald@bch.nhs.uk; melissa.mcpheeters@vanderbilt.edu; john.mitchell@muhc.mcgill.ca; shideh_mofidi@nymc.edu; kmoseley@usc.edu; christine.mueller@nih.gov; andrew.mulberg@fda.hhs.gov; lnerurkar@gmail.com; bogata@uw.edu; anne.pariser@fda.hhs.gov; sprasad@bmrn.com; pridjian@tulane.edu; skr9@cdc.gov; reddyu@mail.nih.gov; frances.rohr@childrens.harvard.edu; rsingh@emory.edu; sandra.sirrs@vch.ca; sstremer@yahoo.com; danilo.tagle@nih.gov; sue.thompson@health.nsw.gov.au; urvtiin@mail.nih.gov; jutz1@fairview.org; f.j.van.spronsen@umcg.nl; vockleyg@upmc.edu; susan.waisbren@childrens.harvard.edu; weglickils@mail.nih.gov; dawhite@wustl.edu; whitley@umn.edu; benjamin.wilfond@seattlechildrens.org; steven.yannicelli@nutricia.com; jmichaelyoung@yahoo.com OI Berry, Gerard/0000-0001-5299-3313; Vockley, Jerry/0000-0002-8180-6457 NR 336 TC 43 Z9 43 U1 5 U2 73 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUN PY 2014 VL 112 IS 2 BP 87 EP 122 DI 10.1016/j.ymgme.2014.02.013 PG 36 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA AI7KF UT WOS:000337067900002 PM 24667081 ER PT J AU Marti, HP Fuscoe, JC Kwekel, JC Anagnostopoulou, A Scherer, A AF Marti, Hans-Peter Fuscoe, James C. Kwekel, Joshua C. Anagnostopoulou, Aikaterini Scherer, Andreas TI Metzincins and related genes in experimental renal ageing: towards a unifying fibrosis classifier across species SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE ageing; CD44; classifier; fibrosis; matrix metalloproteinases; metzincins ID LIFE-CYCLE; MECHANISMS; EXPRESSION; KIDNEY; TARGETS; MORBIDITY; MORTALITY; DISEASE; CD44; RAT AB We have previously described a transcriptomic classifier consisting of metzincins and related genes (MARGS) discriminating kidneys and other organs with or without fibrosis from human biopsies. We now apply our MARGS-based algorithm to a rat model of age-associated interstitial renal fibrosis. Untreated Fisher 344 rats (n = 76) were sacrificed between 2 to 104 weeks of age. For gene expression studies, we used single colour (Cy3) Agilent Whole Rat Genome 4 x 44k microarrays; 4-5 animals of each sex were profiled at each of the following ages: 2, 5, 6, 8, 15, 21, 78 and 104 weeks. Intensity data were subjected to variance stabilization (). Data were analysed with ANOVA and other statistical methods. Sixty MARGS were differentially expressed across age groups. More MARGS were differentially expressed in older males than in older females. Principal component analysis showed gene expression induced segregation of age groups by sex from 6 to 104 weeks of age. The expression level of MMP7 correlated best with fibrosis grade. Severity of fibrosis was determined in 20 animals at 78 and 104 weeks of age. Expression values of 15 of 19 genes of the original classifier present on the Agilent array, in conjunction with linear discriminant analysis, was sufficient to correctly classify these 20 samples into non-fibrosis and fibrosis. Overrepresentation of MMP2 protein and CD44 protein in fibrosis was confirmed by immunofluorescence. Based on these results and our previous work, the MARGS classifier represents a cross-organ and cross-species classifier of fibrosis irrespective of aetiology. This finding provides evidence for a common pathway leading to fibrosis and will help to design a PCR-based clinical test. C1 [Marti, Hans-Peter] Univ Bergen, Dept Clin Med, Bergen, Norway. [Fuscoe, James C.; Kwekel, Joshua C.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Anagnostopoulou, Aikaterini] Univ Bern, Inst Anat, Bern, Switzerland. [Scherer, Andreas] Spheromics, Kontiolahti, Finland. RP Scherer, A (reprint author), Spheromics, Kontiolahti, Finland. EM andreas.scherer@spheromics.com FU Novartis Foundation for Medical-Biological Research; European Community [246539]; FDA Office of Women's Health FX This work was supported by a grant from the Novartis Foundation for Medical-Biological Research to H.-P.M. The position of Aikaterini Anagnostopoulou was funded by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 246539. We thank the FDA Office of Women's Health for support of this project. The findings and conclusions presented in this article are the authors and do not necessarily reflect those of the Food and Drug Administration. NR 30 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JUN PY 2014 VL 29 IS 6 BP 1177 EP 1185 DI 10.1093/ndt/gfu027 PG 9 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA AI7NQ UT WOS:000337079600015 PM 24569495 ER PT J AU Lin, HX Guo, XQ Zhang, SH Dial, SL Guo, L Manjanatha, MG Moore, MM Mei, N AF Lin, Haixia Guo, Xiaoqing Zhang, Suhui Dial, Stacey L. Guo, Lei Manjanatha, Mugimane G. Moore, Martha M. Mei, Nan TI Mechanistic Evaluation of Ginkgo biloba Leaf Extract-Induced Genotoxicity in L5178Y Cells SO TOXICOLOGICAL SCIENCES LA English DT Article DE Ginkgo biloba leaf extract; genotoxicity; quercetin; kaempferol; quercetin 3-beta-d-glucoside; DNA damage; oxidative stress ID MOUSE LYMPHOMA-CELLS; LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY; RAT-LIVER NUCLEI; DNA-DAMAGE; ACTIVE COMPONENTS; COMET ASSAY; PHARMACEUTICAL QUALITY; DIETARY-SUPPLEMENTS; PROOXIDANT ACTIVITY; LIPID-PEROXIDATION AB Ginkgo biloba has been used for many thousand years as a traditional herbal remedy and its extract has been consumed for many decades as a dietary supplement. Ginkgo biloba leaf extract is a complex mixture with many constituents, including flavonol glycosides and terpene lactones. The National Toxicology Program 2-year cancer bioassay found that G. biloba leaf extract targets the liver, thyroid gland, and nose of rodents; however, the mechanism of G. biloba leaf extract-associated carcinogenicity remains unclear. In the current study, the in vitro genotoxicity of G. biloba leaf extract and its eight constituents was evaluated using the mouse lymphoma assay (MLA) and Comet assay. The underlying mechanisms of G. biloba leaf extract-associated genotoxicity were explored. Ginkgo biloba leaf extract, quercetin, and kaempferol resulted in a dose-dependent increase in the mutant frequency and DNA double-strand breaks (DSBs). Western blot analysis confirmed that G. biloba leaf extract, quercetin, and kaempferol activated the DNA damage signaling pathway with increased expression of gamma-H2AX and phosphorylated Chk2 and Chk1. In addition, G. biloba leaf extract produced reactive oxygen species and decreased glutathione levels in L5178Y cells. Loss of heterozygosity analysis of mutants indicated that G. biloba leaf extract, quercetin, and kaempferol treatments resulted in extensive chromosomal damage. These results indicate that G. biloba leaf extract and its two constituents, quercetin and kaempferol, are mutagenic to the mouse L5178Y cells and induce DSBs. Quercetin and kaempferol likely are major contributors to G. biloba leaf extract-induced genotoxicity. C1 [Lin, Haixia; Guo, Xiaoqing; Zhang, Suhui; Dial, Stacey L.; Manjanatha, Mugimane G.; Moore, Martha M.; Mei, Nan] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. [Zhang, Suhui] Shanghai Inst Food & Drug Control, Shanghai 201203, Peoples R China. [Guo, Lei] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Mei, N (reprint author), 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Nan.Mei@fda.hhs.gov RI mei, nan/E-8915-2011; Lin, Haixia /J-4772-2015 OI mei, nan/0000-0002-3501-9014; FU National Center for Toxicological Research (NCTR); Office of International Programs, FDA FX The Postdoctoral Research Program at the National Center for Toxicological Research (NCTR) administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U. S. Food and Drug Administration (FDA) (to H. L.); The International Scientist Exchange Program (ISEP) at the NCTR receiving funding from the Office of International Programs, FDA (to S.Z.). NR 54 TC 3 Z9 4 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2014 VL 139 IS 2 BP 338 EP 349 DI 10.1093/toxsci/kfu037 PG 12 WC Toxicology SC Toxicology GA AI7MO UT WOS:000337075900007 PM 24595819 ER PT J AU de Conti, A Kobets, T Escudero-Lourdes, C Montgomery, B Tryndyak, V Beland, FA Doerge, DR Pogribny, IP AF de Conti, Aline Kobets, Tetyana Escudero-Lourdes, Claudia Montgomery, Beverly Tryndyak, Volodymyr Beland, Frederick Alan Doerge, Daniel R. Pogribny, Igor Petrovych TI Dose- and Time-Dependent Epigenetic Changes in the Livers of Fisher 344 Rats Exposed to Furan SO TOXICOLOGICAL SCIENCES LA English DT Article ID DNA METHYLATION; CARCINOGEN FURAN; GENE-EXPRESSION; MOUSE-LIVER; HEPATOCELLULAR-CARCINOMA; RISK-ASSESSMENT; CELL-CYCLE; IN-VIVO; CANCER; GENOTOXICITY AB The presence of furan in common cooked foods along with evidence from experimental studies that lifetime exposure to furan causes liver tumors in rats and mice has caused concern to regulatory public health agencies worldwide; however, the mechanisms of the furan-induced hepatocarcinogenicity remain unclear. The goal of the present study was to investigate whether or not long-term exposure to furan causes epigenetic alterations in rat liver. Treating of male Fisher 344 rats by gavage 5 days per week with 0, 0.92, 2.0, or 4.4 mg furan/kg body weight (bw)/day resulted in dose- and time-dependent epigenetic changes consisting of alterations in DNA methylation and histone lysine methylation and acetylation, altered expression of chromatin modifying genes, and gene-specific methylation. Specifically, exposure to furan at doses 0.92, 2.0, or 4.4 mg furan/kg bw/day caused global DNA demethylation after 360 days of treatment. There was also a sustained decrease in the levels of histone H3 lysine 9 and H4 lysine 20 trimethylation after 180 and 360 days of furan exposure, and a marked reduction of histone H3 lysine 9 and H3 lysine 56 acetylation after 360 days at 4.4 mg/kg bw/day. These histone modification changes were accompanied by a reduced expression of Suv39h1, Prdm2, and Suv4-20h2 histone methyltransferases and Ep300 and Kat2a histone acetyltransferases. Additionally, furan at 2.0 and 4.4 mg/kg bw/day induced hypermethylation-dependent down-regulation of the Rassf1a gene in the livers after 180 and 360 days. These findings indicate possible involvement of dose- and time-dependent epigenetic modifications in the furan hepatotoxicity and carcinogenicity. Key words: Furan; liver; rat; epigenetic changes. C1 [de Conti, Aline; Kobets, Tetyana; Escudero-Lourdes, Claudia; Montgomery, Beverly; Tryndyak, Volodymyr; Beland, Frederick Alan; Doerge, Daniel R.; Pogribny, Igor Petrovych] NCTR, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Escudero-Lourdes, Claudia] Univ Autonoma San Luis Potosi, Fac Ciencias Quim, San Luis Potosi 78240, Mexico. RP Pogribny, IP (reprint author), NCTR, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov FU National Toxicology Program (NTP); Foodand Drug Administration (FDA); National Institute of Environmental Health Sciences (NIEHS) (FDA IAG) [224-12-0003/NIEHS]; National Institute of Environmental Health Sciences (NIEHS) (IAG) [AES12013] FX This work was carried out under the auspices of the National Toxicology Program (NTP) and supported by an Interagency Agreement between Foodand Drug Administration (FDA) and National Institute of Environmental Health Sciences (NIEHS) (FDA IAG no. 224-12-0003/NIEHS IAG no. AES12013) and supported in part by appointment (A.d.C., T. K.) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education (ORISE). NR 39 TC 5 Z9 5 U1 0 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2014 VL 139 IS 2 BP 371 EP 380 DI 10.1093/toxsci/kfu044 PG 10 WC Toxicology SC Toxicology GA AI7MO UT WOS:000337075900010 ER PT J AU Gandhi, SV Rodriguez, W Khan, M Polli, JE AF Gandhi, Shivani V. Rodriguez, William Khan, Mansoor Polli, James E. TI Considerations for a Pediatric Biopharmaceutics Classification System (BCS): Application to Five Drugs SO AAPS PHARMSCITECH LA English DT Article DE absorption; bioavailability; bioequivalence; biopharmaceutics classification system; pediatric ID HIGHLY EMETOGENIC CHEMOTHERAPY; CYSTIC-FIBROSIS PATIENTS; YOUNG-CHILDREN; ANTIEMETIC EFFICACY; DOLASETRON MESYLATE; IN-VITRO; PHARMACOKINETICS; KETOPROFEN; BIOAVAILABILITY; CIPROFLOXACIN AB It has been advocated that biopharmaceutic risk assessment should be conducted early in pediatric product development and synchronized with the adult product development program. However, we are unaware of efforts to classify drugs into a Biopharmaceutics Classification System (BCS) framework for pediatric patients. The objective was to classify five drugs into a potential BCS. These five drugs were selected since both oral and intravenous pharmacokinetic data were available for each drug, and covered the four BCS classes in adults. Literature searches for each drug were conducted using Medline and applied to classify drugs with respect to solubility and permeability in pediatric subpopulations. Four pediatric subpopulations were considered: neonates, infants, children, and adolescents. Regarding solubility, dose numbers were calculated using a volume for each subpopulation based on body surface area (BSA) relative to 250 ml for a 1.73 m(2) adult. Dose numbers spanned a range of values, depending upon the pediatric dose formula and subpopulation. Regarding permeability, pharmacokinetic literature data required assumptions and decisions about data collection. Using a devised pediatric BCS framework, there was agreement in adult and pediatric BCS class for two drugs, azithromycin (class 3) and ciprofloxacin (class 4). There was discordance for the three drugs that have high adult permeability since all pediatric permeabilities were low: dolasetron (class 3 in pediatric), ketoprofen (class 4 in pediatric), and voriconazole (class 4 in pediatric). A main contribution of this work is the identification of critical factors required for a pediatric BCS. C1 [Gandhi, Shivani V.; Polli, James E.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Rodriguez, William; Khan, Mansoor] US FDA, Silver Spring, MD 20993 USA. RP Polli, JE (reprint author), Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. EM jpolli@rx.umaryland.edu NR 44 TC 5 Z9 5 U1 3 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD JUN PY 2014 VL 15 IS 3 BP 601 EP 611 DI 10.1208/s12249-014-0084-0 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI3AE UT WOS:000336729800009 PM 24557773 ER PT J AU Van Buskirk, GA Asotra, S Balducci, C Basu, P DiDonato, G Dorantes, A Eickhoff, WM Ghosh, T Gonzalez, MA Henry, T Howard, M Kamm, J Laurenz, S MacKenzie, R Mannion, R Noonan, PK Ocheltree, T Pai, U Poska, RP Putnam, ML Raghavan, RR Ruegger, C Sanchez, E Shah, VP Shao, ZJ Somma, R Tammara, V Thombre, AG Thompson, B Timko, RJ Upadrashta, S Vaithiyalingam, S AF Van Buskirk, Glenn A. Asotra, Satish Balducci, Christopher Basu, Prabir DiDonato, Gerald Dorantes, Angelica Eickhoff, W. Mark Ghosh, Tapash Gonzalez, Mario A. Henry, Theresa Howard, Matthew Kamm, Jason Laurenz, Steven MacKenzie, Ryan Mannion, Richard Noonan, Patrick K. Ocheltree, Terrance Pai, Umesh Poska, Richard P. Putnam, Michael L. Raghavan, Ramani R. Ruegger, Colleen Sanchez, Eric Shah, Vinod P. Shao, Zezhi Jesse Somma, Russell Tammara, Vijay Thombre, Avinash G. Thompson, Bruce Timko, Robert J. Upadrashta, Satyam Vaithiyalingam, Sivakumar TI Best Practices for the Development, Scale-up, and Post-approval Change Control of IR and MR Dosage Forms in the Current Quality-by-Design Paradigm SO AAPS PHARMSCITECH LA English DT Article DE CMC; ICH; IVIVC; PAT; QbD AB In this whitepaper, the Manufacturing Technical Committee of the Product Quality Research Institute provides information on the common, best practices in use today in the development of high-quality chemistry, manufacturing and controls documentation. Important topics reviewed include International Conference on Harmonization, in vitro-in vivo correlation considerations, quality-by-design approaches, process analytical technologies and current scale-up, and process control and validation practices. It is the hope and intent that this whitepaper will engender expanded dialog on this important subject by the pharmaceutical industry and its regulatory bodies. C1 [Van Buskirk, Glenn A.] Nonclin Drug Dev Consulting Serv LLC, Basking Ridge, NJ 07920 USA. [Asotra, Satish] AHI Inc, Brampton, ON L6W 4K4, Canada. [Balducci, Christopher; Ruegger, Colleen] Novartis Pharmaceut, E Hanover, NJ 07936 USA. [Basu, Prabir] Natl Inst Pharmaceut Technol & Engn NIPTE, Prospect, IL 60056 USA. [DiDonato, Gerald] Bristol Myers Squibb Co, Pennington, NJ 08534 USA. [Dorantes, Angelica; Ghosh, Tapash; Ocheltree, Terrance] US FDA, Silver Spring, MD 20993 USA. [Eickhoff, W. Mark; Thompson, Bruce] Merck & Co Inc, West Point, PA 19486 USA. [Gonzalez, Mario A.] PKinet Int Inc, Pembroke Pines, FL 33027 USA. [Howard, Matthew] McNeil Consumer Healthcare, Ft Washington, PA USA. [Kamm, Jason] Summit Pharma Solut LLC, South Windsor, CT USA. [Laurenz, Steven; Poska, Richard P.] AbbVie, N Chicago, IL 60064 USA. [MacKenzie, Ryan] Janssen Res & Dev LLC, Spring House, PA 19477 USA. [Mannion, Richard] Purdue Pharma LP, Cranbury, NJ 08512 USA. [Noonan, Patrick K.] PK Noonan & Associates LLC, Williamsburg, VA 23188 USA. [Pai, Umesh] Sun Pharma USA, Cranbury, NJ 08512 USA. [Putnam, Michael L.] Boehringer Ingelheim VetMed Inc, St Joseph, MO 64506 USA. [Raghavan, Ramani R.] Genentech Inc, San Francisco, CA 94080 USA. [Sanchez, Eric] Janssen Ortho LLC, Gurabo, PR 00778 USA. [Shao, Zezhi Jesse] Arena Pharmaceut, San Diego, CA 92121 USA. [Somma, Russell] Somma Tech Consulting, Somerset, NJ 08873 USA. [Tammara, Vijay] Nuron Biotech Inc, Exton, PA 19341 USA. [Thombre, Avinash G.] Pfizer Inc, Groton, CT 06340 USA. [Timko, Robert J.] AstraZeneca LP, Wilmington, DE 19850 USA. [Upadrashta, Satyam] Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. [Vaithiyalingam, Sivakumar] Teva Pharmaceut, Pomona, NY 10970 USA. RP Van Buskirk, GA (reprint author), Nonclin Drug Dev Consulting Serv LLC, Basking Ridge, NJ 07920 USA. EM glennvb@optonline.net NR 14 TC 2 Z9 2 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD JUN PY 2014 VL 15 IS 3 BP 665 EP 693 DI 10.1208/s12249-014-0087-x PG 29 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI3AE UT WOS:000336729800015 PM 24578237 ER PT J AU Saini, S Katagiri, NH Guerrera, MF Pandey, GS Guelcher, C Dandekar, S Simhadri, VL Kimchi-Sarfaty, C Sauna, ZE AF Saini, Surbhi Katagiri, Nobuko H. Guerrera, Michael F. Pandey, Gouri S. Guelcher, Christine Dandekar, Sugandha Simhadri, Vijaya L. Kimchi-Sarfaty, Chava Sauna, Zuben E. TI GENETIC DETERMINANTS OF IMMUNOGENICITY TO FACTOR IX DURING THE TREATMENT OF HEMOPHILIA B SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Saini, Surbhi; Guerrera, Michael F.; Guelcher, Christine] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Saini, Surbhi; Katagiri, Nobuko H.; Pandey, Gouri S.; Simhadri, Vijaya L.; Kimchi-Sarfaty, Chava; Sauna, Zuben E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Dandekar, Sugandha] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 97 BP E46 EP E47 PG 2 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600095 ER PT J AU Bruno, R Mentre, F Tannenbaum, S Wang, Y Corrigan, B Mager, DE AF Bruno, R. Mentre, F. Tannenbaum, S. Wang, Y. Corrigan, B. Mager, D. E. TI The ISoP Standards and Best Practices Committee SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID DRUG DEVELOPMENT; PHARMACOMETRICS AB The mission of the International Society of Pharmacometrics (ISoP) Standards and Best Practices Committee is to provide best practices and recommendations for standard pharmacometric analyses-e.g., population pharmacokinetics/pharmacodynamics (PK/PD), exposure-response, disease models-with the goal of increasing consistency, productivity, quality, communication, and impact of pharmacometrics on decision making. We present the progress and plans of the committee and call for volunteers to start new initiatives. C1 [Bruno, R.] Pharsight, Pharsight Consulting Serv, Marseille, France. [Mentre, F.] INSERM, UMR 1137, Paris, France. [Mentre, F.] Univ Paris Diderot, Paris, France. [Tannenbaum, S.] Astellas Pharma Global Dev, Northbrook, IL USA. [Wang, Y.] US FDA, Off Clin Pharmacol, Div Pharmacometr, Silver Spring, MD USA. [Corrigan, B.] Pfizer Global Res, Groton, CT USA. [Mager, D. E.] SUNY Buffalo, Buffalo, NY 14260 USA. RP Bruno, R (reprint author), Pharsight, Pharsight Consulting Serv, Marseille, France. EM rbruno@certara.com NR 6 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2014 VL 95 IS 6 BP 581 EP 582 DI 10.1038/clpt.2014.65 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH8VC UT WOS:000336415300015 PM 24842638 ER PT J AU Kasza, KA Bansal-Travers, M O'Connor, RJ Compton, WM Kettermann, A Borek, N Fong, GT Cummings, KM Hyland, AJ AF Kasza, Karin A. Bansal-Travers, Maansi O'Connor, Richard J. Compton, Wilson M. Kettermann, Anna Borek, Nicolette Fong, Geoffrey T. Cummings, K. Michael Hyland, Andrew J. TI Cigarette Smokers' Use of Unconventional Tobacco Products and Associations With Quitting Activity: Findings From the ITC-4 U.S. Cohort SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID 4 COUNTRY SURVEY; SMOKELESS TOBACCO; SMOKING-CESSATION; ELECTRONIC CIGARETTES; DELIVERY-SYSTEMS; POLYTOBACCO USE; PATTERNS; SNUS; INITIATION; REDUCTION AB The purpose of this study was to evaluate the prevalence and correlates of use of nicotine-containing tobacco products such as cigars, pipe tobacco, and cigarettes that promise less exposure to toxins; e-cigarettes; and smokeless tobacco products among a cohort of conventional cigarette smokers followed over the past decade. We also evaluated associations between use of such products and cigarette quitting. Participants were 6,110 adult smokers in the United States, who were interviewed as part of the International Tobacco Control Four Country Survey between 2002 and 2011. Respondents reported their concurrent use of other smoked tobacco products (including cigars, pipe tobacco, and cigarillos), smokeless tobacco products (including chewing tobacco, snus, and snuff), unconventional cigarettes (including Omni, Accord, and Eclipse), and electronic cigarettes. Prevalence and correlates of use and associations between use and cigarette quitting were assessed using regression analyses via generalized estimating equations. Most cigarette smokers did not use unconventional tobacco products, although use of any of these products started to rise at the end of the study period (2011). For each type of tobacco product evaluated, use was most prevalent among those aged 18-24 years. Smokers who did use unconventional tobacco products did not experience a clear cessation advantage. During the past decade, relatively few cigarette smokers reported also using other tobacco products. Those that did use such products were no more likely to stop using conventional cigarettes compared with those who did not use such products. C1 [Kasza, Karin A.] Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. [Bansal-Travers, Maansi; O'Connor, Richard J.; Hyland, Andrew J.] Roswell Pk Canc Inst, Dept Hlth Behav, Buffalo, NY 14263 USA. [Compton, Wilson M.] NIDA, NIH, Bethesda, MD 20892 USA. [Kettermann, Anna; Borek, Nicolette] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. [Fong, Geoffrey T.] Univ Waterloo, Dept Psychol, Waterloo, CA USA. [Fong, Geoffrey T.] Ontario Inst Canc Res, Toronto, ON, Canada. [Cummings, K. Michael] Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Kasza, KA (reprint author), Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. EM karin.kasza@roswellpark.org RI Fong, Geoffrey/H-2810-2014; O'Connor, Richard/A-6961-2009 OI Fong, Geoffrey/0000-0001-9098-6472; FU Federal funds from the National Institute on Drug Abuse; National Institutes of Health; U.S. Food and Drug Administration, Department of Health and Human Services [HHSN271201100027C]; U.S. National Cancer Institute [P50 CA111326, P01 CA138389, R01 CA100362, R01 CA125116]; Canadian Institutes of Health Research [57897, 79551, 115016]; National Health and Medical Research Council of Australia [265903, 450110, 1005922]; Cancer Research UK [C312/A3726, C312/A6465, C312/A11039]; Robert Wood Johnson Foundation [045734]; Canadian Tobacco Control Research Initiative [014578]; Ontario Institute for Cancer Research; Canadian Cancer Society Research Institute FX This study was supported by Federal funds from the National Institute on Drug Abuse, National Institutes of Health, and the U.S. Food and Drug Administration, Department of Health and Human Services, under Contract No. HHSN271201100027C. The ITC Four Country Survey has been funded by the U.S. National Cancer Institute (P50 CA111326, P01 CA138389, R01 CA100362, R01 CA125116), Canadian Institutes of Health Research (57897, 79551, and 115016), National Health and Medical Research Council of Australia (265903, 450110, and 1005922), Cancer Research UK (C312/A3726, C312/A6465, and C312/A11039), Robert Wood Johnson Foundation (045734), and Canadian Tobacco Control Research Initiative (014578). Geoffrey T. Fong is supported by a Senior Investigator Award from the Ontario Institute for Cancer Research and a Prevention Scientist Award from the Canadian Cancer Society Research Institute. The roles of Wilson Compton, Nicolette Borek, and Anna Kettermann on this article are solely as collaborators on HHSN271201100027C, with no involvement in any other cited projects. NR 46 TC 13 Z9 13 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUN PY 2014 VL 16 IS 6 BP 672 EP 681 DI 10.1093/ntr/ntt212 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA AH9UX UT WOS:000336491000006 PM 24376276 ER PT J AU Stoyanova-Slavova, IB Slavov, SH Pearce, B Buzatu, DA Beger, RD Wilkes, JG AF Stoyanova-Slavova, Iva B. Slavov, Svetoslav H. Pearce, Bruce Buzatu, Dan A. Beger, Richard D. Wilkes, Jon G. TI PARTIAL LEAST SQUARE AND K-NEAREST NEIGHBOR ALGORITHMS FOR IMPROVED 3D QUANTITATIVE SPECTRAL DATA-ACTIVITY RELATIONSHIP CONSENSUS MODELING OF ACUTE TOXICITY SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE Aquatic toxicology; Computational toxicology; Multivariate statistic; 3D quantitative spectral data-activity relationship (QSDAR); Consensus modeling ID DAPHNIA-MAGNA; AQUATIC TOXICITY; ORGANIC-CHEMICALS; QSAR; CLASSIFICATION; DESCRIPTORS; ANILINES; NARCOSIS; BINDING; HEART AB A diverse set of 154 chemicals that included US Food and Drug Administration-regulated compounds tested for their aquatic toxicity in Daphnia magna were modeled by a 3-dimensional quantitative spectral data-activity relationship (3D-QSDAR). Two distinct algorithms, partial least squares (PLS) and Tanimoto similarity-based k-nearest neighbors (KNN), were used to process bin occupancy descriptor matrices obtained after tessellation of the 3D-QSDAR space into regularly sized bins. The performance of models utilizing bins ranging in size from 2ppmx2ppmx0.5 angstrom to 20ppmx20ppmx2.5 angstrom was explored. Rigorous quality-control criteria were imposed: 1) 100 randomized 20% hold-out test sets were generated and the average R-test(2) of the respective models was used as a measure of their performance, and 2) a Y-scrambling procedure was used to identify chance correlations. A consensus between the best-performing composite PLS model using 0.5 angstrom x14ppmx14ppm bins and 10 latent variables (average R-test(2)=0.770) and the best composite KNN model using 0.5 angstrom x8ppmx8ppm and 2 neighbors (average R-test(2)=0.801) offered an improvement of about 7.5% (R-test consensus(2)=0.845). Projection of the most frequently occurring bins on the standard coordinate space indicated that the presence of a primary or secondary amino groupsubstituted aromatic systemswould result in an increased toxic effect in Daphnia. The presence of a second aromatic ring with highly electronegative substituents 5 angstrom to 7 angstrom apart from the first ring would lead to a further increase in toxicity. Environ Toxicol Chem 2014;33:1271-1282. (c) 2014 SETAC C1 [Stoyanova-Slavova, Iva B.; Slavov, Svetoslav H.; Pearce, Bruce; Buzatu, Dan A.; Beger, Richard D.; Wilkes, Jon G.] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. EM Jon.Wilkes@fda.hhs.gov NR 48 TC 7 Z9 7 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-7268 EI 1552-8618 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD JUN PY 2014 VL 33 IS 6 BP 1271 EP 1282 DI 10.1002/etc.2534 PG 12 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA AH2FM UT WOS:000335936900002 PM 24464801 ER PT J AU Wang, W Joslin, SN Pybus, C Evans, AS Lichaa, F Brautigam, CA Hansen, EJ AF Wang, Wei Joslin, Stephanie N. Pybus, Christine Evans, Amanda S. Lichaa, Flora Brautigam, Chad A. Hansen, Eric J. TI Identification of an Outer Membrane Lipoprotein Involved in Nasopharyngeal Colonization by Moraxella catarrhalis in an Animal Model SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN EPITHELIAL-CELLS; OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY-TRACT PATHOGEN; GLOBAL GENE-EXPRESSION; BRANHAMELLA-CATARRHALIS; IMMUNE-RESPONSE; OTITIS-MEDIA; PROTEIN-E; IN-VITRO; NEISSERIA-MENINGITIDIS AB Colonization of the human nasopharynx by Moraxella catarrhalis is presumed to involve attachment of this bacterium to the mucosa. DNA microarray analysis was used to determine whether attachment of M. catarrhalis to human bronchial epithelial (HBE) cells in vitro affected gene expression in this bacterium. Attachment affected expression of at least 454 different genes, with 163 being upregulated and 291 being downregulated. Among the upregulated genes was one (ORF113) previously annotated as encoding a protein with some similarity to outer membrane protein A (OmpA). The protein encoded by ORF113 was predicted to have a signal peptidase II cleavage site, and globomycin inhibition experiments confirmed that this protein was indeed a lipoprotein. The ORF113 protein also contained a predicted peptidoglycan-binding domain in its C-terminal half. The use of mutant and recombinant M. catarrhalis strains confirmed that the ORF113 protein was present in outer membrane preparations, and this protein was also shown to be at least partially exposed on the bacterial cell surface. A mutant unable to produce the ORF113 protein showed little or no change in its growth rate in vitro, in its ability to attach to HBE cells in vitro, or in its autoagglutination characteristics, but it did exhibit a reduced ability to survive in the chinchilla nasopharynx. This is the first report of a lipoprotein essential to the ability of M. catarrhalis to persist in an animal model. C1 [Wang, Wei; Lichaa, Flora] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Joslin, Stephanie N.; Pybus, Christine; Hansen, Eric J.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Evans, Amanda S.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Brautigam, Chad A.] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA. RP Hansen, EJ (reprint author), Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. EM wei02.wang@fda.hhs.gov; eric.hansen@utsouthwestern.edu FU U.S. Public Health Service [AI036344, 5 T32 AI007520, 5 T32 AI005284]; FDA operation funds FX This study was supported by U.S. Public Health Service grant no. AI036344 to E.J.H. S.N.J. was supported by U.S. Public Health Service training grants 5 T32 AI007520 and 5 T32 AI005284. F.L. was supported by FDA operation funds to LBP-Wang. NR 81 TC 4 Z9 4 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2014 VL 82 IS 6 BP 2287 EP 2299 DI 10.1128/IAI.01745-14 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AH8HN UT WOS:000336378100015 PM 24643539 ER PT J AU Murphy, MV Du, DY Hua, W Cortez, KJ Butler, MG Davis, RL DeCoster, T Johnson, L Li, LL Nakasato, C Nordin, JD Ramesh, M Schum, M Von Worley, A Zinderman, C Platt, R Klompas, M AF Murphy, Michael V. Du, Dongyi (Tony) Hua, Wei Cortez, Karoll J. Butler, Melissa G. Davis, Robert L. DeCoster, Thomas Johnson, Laura Li, Lingling Nakasato, Cynthia Nordin, James D. Ramesh, Mayur Schum, Michael Von Worley, Ann Zinderman, Craig Platt, Richard Klompas, Michael TI The Utility of Claims Data for Infection Surveillance following Anterior Cruciate Ligament Reconstruction SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID SURGICAL-SITE INFECTIONS; SEPTIC ARTHRITIS; UNITED-STATES; HUMAN TISSUE; ALLOGRAFT; SURGERY; RISK; DIAGNOSIS; GRAFT; IDENTIFICATION AB Objective.To explore the feasibility of identifying anterior cruciate ligament (ACL) allograft implantations and infections using claims.Design.Retrospective cohort study.Methods.We identified ACL reconstructions using procedure codes at 6 health plans from 2000 to 2008. We then identified potential infections using claims-based indicators of infection, including diagnoses, procedures, antibiotic dispensings, specialty consultations, emergency department visits, and hospitalizations. Patients' medical records were reviewed to determine graft type, validate infection status, and calculate sensitivity and positive predictive value (PPV) for indicators of ACL allografts and infections.Results.A total of 11,778 patients with codes for ACL reconstruction were identified. After chart review, PPV for ACL reconstruction was 96% (95% confidence interval [CI], 94%-97%). Of the confirmed ACL reconstructions, 39% (95% CI, 35%-42%) used allograft tissues. The deep infection rate after ACL reconstruction was 1.0% (95% CI, 0.7%-1.4%). The odds ratio of infection for allografts versus autografts was 0.41 (95% CI, 0.19-0.78). Sensitivity of individual claims-based indicators for deep infection after ACL reconstruction ranged from 0% to 75% and PPV from 0% to 100%. Claims-based infection indicators could be combined to enhance sensitivity or PPV but not both.Conclusions.While claims data accurately identify ACL reconstructions, they poorly distinguish between allografts and autografts and identify infections with variable accuracy. Claims data could be useful to monitor infection trends after ACL reconstruction, with different algorithms optimized for different surveillance goals. C1 [Murphy, Michael V.; Li, Lingling; Platt, Richard; Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Murphy, Michael V.; Li, Lingling; Platt, Richard; Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Du, Dongyi (Tony); Hua, Wei; Zinderman, Craig] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Cortez, Karoll J.] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Butler, Melissa G.; Davis, Robert L.] Kaiser Permanente Georgia, Ctr Hlth Res Southeast, Atlanta, GA USA. [DeCoster, Thomas] Univ New Mexico, Sch Med, Dept Orthopaed & Rehabil, Albuquerque, NM 87131 USA. [Johnson, Laura; Ramesh, Mayur] Henry Ford Hlth Syst, Ctr Hlth Serv Res, Detroit, MI USA. [Nakasato, Cynthia] Kaiser Permanente Hawaii, Ctr Hlth Res, Honolulu, HI USA. [Nordin, James D.] HealthPartners Inst Educ & Res, Minneapolis, MN USA. [Schum, Michael; Von Worley, Ann] LCF Res, Hlth Serv Res Div, Albuquerque, NM USA. RP Murphy, MV (reprint author), Harvard Pilgrim Hlth Care Inst, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM michael_murphy@harvardpilgrim.org FU Food and Drug Administration [HHSF223200810026I/TO6, HHSF22301005T] FX This study was supported through funding from contracts HHSF223200810026I/TO6 and HHSF22301005T from the Food and Drug Administration. NR 40 TC 3 Z9 5 U1 3 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN 1 PY 2014 VL 35 IS 6 BP 652 EP 659 DI 10.1086/676430 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AG8UK UT WOS:000335693500004 PM 24799641 ER PT J AU Sun, HH Vesely, R Taminiau, J Szitanyi, P Papadopoulos, EJ Isaac, M Klein, A Uzu, S Griebel, D Mulberg, AE AF Sun, Haihao Vesely, Richard Taminiau, Jan Szitanyi, Peter Papadopoulos, Elektra J. Isaac, Maria Klein, Agnes Uzu, Shinobu Griebel, Donna Mulberg, Andrew E. CA Int Inflammatory Bowel Dis Working TI Steps Toward Harmonization for Clinical Development of Medicines in Pediatric Ulcerative Colitis-A Global Scientific Discussion, Part 1: Efficacy Endpoints and Disease Outcome Assessments SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE biomarkers; disease outcome assessments; endpoints; pediatric ulcerative colitis; surrogate endpoint ID INFLAMMATORY-BOWEL-DISEASE; ACTIVITY INDEX; PROSPECTIVE MULTICENTER; ENDOSCOPIC SEVERITY; FECAL LACTOFERRIN; CHILDREN; MARKERS; TRIALS; REMISSION; ADULTS AB Objectives:There is a pressing need for drug development in pediatric ulcerative colitis (UC). Lack of scientific consensus on efficacy endpoints and disease outcome assessments presents a hurdle for global drug development in pediatric UC. Scientists from 4 regulatory agencies convened an International Inflammatory Bowel Disease Working Group (i-IBD Working Group) to harmonize present thinking about various aspects of drug development in pediatric UC globally.Methods:The i-IBD Working Group was convened in 2012 by scientists from the US Food and Drug Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals and Medical Devices Agency of Japan. The members of this group considered reasons for differences in their acceptance of efficacy endpoints and disease activity indices used in pediatric UC, reviewed the available literature, and developed consensus opinions regarding approaches for evaluating outcomes in pediatric UC trials.Results:There is lack of harmonization in using efficacy endpoint and outcome assessments including disease activity indices to assess clinical benefit in pediatric UC trials. Many disease activity indices have been developed, but their biometric properties, such as responsiveness, reliability, and validity, have not been properly validated. Biomarkers, such as fecal calprotectin and lactoferrin, are being investigated for their potential as noninvasive surrogate endpoints in UC.Conclusions:Consensus on the efficacy endpoints, disease activity indices, and outcome assessments is needed for globalization of pediatric UC trials. The i-IBD Working Group offers several perspectives to facilitate harmonization across regions. The development of noninvasive biomarkers as reliable surrogate endpoints needs to be explored further. C1 [Sun, Haihao; Papadopoulos, Elektra J.; Griebel, Donna; Mulberg, Andrew E.] US FDA, Silver Spring, MD 20993 USA. [Vesely, Richard; Taminiau, Jan; Szitanyi, Peter; Isaac, Maria] European Med Agcy, London, England. [Klein, Agnes] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Uzu, Shinobu] Pharmaceut & Med Devices Agcy, Tokyo, Japan. RP Mulberg, AE (reprint author), US FDA, Div Gastroenterol & Inborn Errors Prod, OND CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Andrew.Mulberg@fda.hhs.gov NR 29 TC 3 Z9 3 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUN PY 2014 VL 58 IS 6 BP 679 EP 683 DI 10.1097/MPG.0000000000000306 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AH6SS UT WOS:000336261600010 PM 24866781 ER PT J AU Sun, HH Vesely, R Nelson, RM Taminiau, J Szitanyi, P Isaac, M Klein, A Uzu, S Griebel, D Mulberg, AE AF Sun, Haihao Vesely, Richard Nelson, Robert M. Taminiau, Jan Szitanyi, Peter Isaac, Maria Klein, Agnes Uzu, Shinobu Griebel, Donna Mulberg, Andrew E. CA Int Inflammatory Bowel Dis Working TI Steps Toward Harmonization for Clinical Development of Medicines in Pediatric Ulcerative Colitis-A Global Scientific Discussion, Part 2: Data Extrapolation, Trial Design, and Pharmacokinetics SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE data extrapolation; ethics; pediatric ulcerative colitis; pharmacokinetics; trial design ID INFLAMMATORY-BOWEL-DISEASE; PLACEBO-CONTROLLED TRIALS; ACTIVE-CONTROL TRIALS; GUIDELINES; MANAGEMENT; CHILDREN; THERAPY; ISSUES; ADULTS; IBD AB Objectives:To facilitate global drug development, the International Pediatric Inflammatory Bowel Disease Working Group (i-IBD Working Group) discussed data extrapolation, trial design, and pharmacokinetic (PK) considerations for drugs intended to treat pediatric ulcerative colitis (UC), and considered possible approaches toward harmonized drug development.Methods:Representatives from the US Food and Drug Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals and Medical Devices Agency of Japan convened monthly to explore existing regulatory approaches, reviewed the results of a literature search, and provided perspectives on pediatric UC drug development based on the available medical literature.Results:Although pediatric UC, when compared with UC in adults, has a similar disease progression and response to intervention, the similarity of the exposure-response relation has not been adequately established. Consequently, clinical endpoints should be selected to optimally assess efficacy in children. The inclusion of a placebo control in pediatric trials to assure assay sensitivity may be appropriate under limited circumstances. In clinical studies, although the drug under investigation could provide possible direct benefit, placebo treatment should present no more than a minor increase over minimal risk to children with UC.Conclusions:Partial extrapolation of efficacy from informative adult studies may be appropriate. Placebo-controlled efficacy trials are scientifically and ethically appropriate for pediatric UC given appropriate patient selection and the use of early escape. Clinical studies in pediatric UC may include initial dose-finding studies and exposure-response modeling followed by an efficacy and safety study to further explore the exposure-response relation. C1 [Sun, Haihao; Nelson, Robert M.; Griebel, Donna; Mulberg, Andrew E.; Int Inflammatory Bowel Dis Working] US FDA, Silver Spring, MD 20993 USA. [Vesely, Richard; Taminiau, Jan; Szitanyi, Peter; Isaac, Maria] European Med Agcy, London, England. [Klein, Agnes] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Uzu, Shinobu] Pharmaceut & Med Devices Agcy, Tokyo, Japan. RP Mulberg, AE (reprint author), US FDA, Div Gastroenterol & Inborn Errors Prod, OND CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Andrew.Mulberg@fda.hhs.gov NR 19 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUN PY 2014 VL 58 IS 6 BP 684 EP 688 DI 10.1097/MPG.0000000000000322 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AH6SS UT WOS:000336261600011 PM 24866782 ER PT J AU Walsh, DL Duraiswamy, N Vesnovsky, O Topoleski, LDT AF Walsh, Donna L. Duraiswamy, Nandini Vesnovsky, Oleg Topoleski, L. D. Timmie TI Pacemaker and Defibrillator Lead Tip Interactions in Porcine Cardiac Tissue and Tissue Substitute on the Bench SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME LA English DT Article C1 [Walsh, Donna L.; Duraiswamy, Nandini; Vesnovsky, Oleg; Topoleski, L. D. Timmie] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Topoleski, L. D. Timmie] Univ Maryland Baltimore Cty, Dept Mech Engn, Baltimore, MD 21250 USA. RP Walsh, DL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 1932-6181 EI 1932-619X J9 J MED DEVICES JI J. Med. Devices PD JUN PY 2014 VL 8 IS 2 AR 020912 DI 10.1115/1.4027013 PG 2 WC Engineering, Biomedical SC Engineering GA AH3SO UT WOS:000336045900013 ER PT J AU Price, GE Lo, CY Misplon, JA Epstein, SL AF Price, Graeme E. Lo, Chia-Yun Misplon, Julia A. Epstein, Suzanne L. TI Mucosal Immunization with a Candidate Universal Influenza Vaccine Reduces Virus Transmission in a Mouse Model SO JOURNAL OF VIROLOGY LA English DT Article ID A VIRUS; T-CELLS; HETEROSUBTYPIC IMMUNITY; GUINEA-PIG; INFECTION; MICE; PROTECTION; CHALLENGE; PROTEIN; H5N1 AB Pandemic influenza is a major public health concern, but conventional strain-matched vaccines are unavailable early in a pandemic. Candidate "universal" vaccines targeting the viral antigens nucleoprotein (NP) and matrix 2 (M2), which are conserved among all influenza A virus strains and subtypes, could be manufactured in advance for use at the onset of a pandemic. These vaccines do not prevent infection but can reduce disease severity, deaths, and virus titers in the respiratory tract. We hypothesized that such immunization may reduce virus transmission from vaccinated, infected animals. To investigate this hypothesis, we studied mouse models for direct-contact and airborne transmission of H1N1 and H3N2 influenza viruses. We established conditions under which virus transmission occurs and showed that transmission efficiency is determined in part at the level of host susceptibility to infection. Our findings indicate that virus transmission between mice has both airborne and direct-contact components. Finally, we demonstrated that immunization with recombinant adenovirus vectors expressing NP and M2 significantly reduced the transmission of virus to cohoused, unimmunized mice in comparison to controls. These findings have broad implications for the impact of conserved-antigen vaccines, not only in protecting the vaccinated individual but also in protecting others by limiting influenza virus transmission and potentially reducing the size of epidemics. C1 [Price, Graeme E.; Lo, Chia-Yun; Misplon, Julia A.; Epstein, Suzanne L.] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. RP Price, GE (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. EM graeme.price@fda.hhs.gov FU FDA CBER Pandemic Influenza Initiative FX This study was supported by FDA CBER Pandemic Influenza Initiative funding. NR 64 TC 14 Z9 14 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2014 VL 88 IS 11 BP 6019 EP 6030 DI 10.1128/JVI.03101-13 PG 12 WC Virology SC Virology GA AH2SB UT WOS:000335970300012 PM 24623430 ER PT J AU Le Nouen, C Hillyer, P Brock, LG Winter, CC Rabin, RL Collins, PL Buchholz, UJ AF Le Nouen, Cyril Hillyer, Philippa Brock, Linda G. Winter, Christine C. Rabin, Ronald L. Collins, Peter L. Buchholz, Ursula J. TI Human Metapneumovirus SH and G Glycoproteins Inhibit Macropinocytosis-Mediated Entry into Human Dendritic Cells and Reduce CD4(+) T Cell Activation SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNOSUPPRESSION IN-VITRO; RESPIRATORY-TRACT DISEASE; VIRAL GLYCOPROTEINS; FLOW-CYTOMETRY; VIRUS ENTRY; ADULTS; INFECTION; CHILDREN; SURFACE; MEMORY AB Human metapneumovirus (HMPV) is a major etiologic agent of respiratory disease worldwide. HMPV reinfections are common in healthy adults and children, suggesting that the protective immune response to HMPV is incomplete and short-lived. We used gene-deletion viruses to evaluate the role of the attachment G and small hydrophobic SH glycoproteins on virus uptake by primary human monocyte-derived dendritic cells (MDDC) in vitro and on subsequent MDDC maturation and activation of autologous T cells. HMPV with deletion of G and SH (Delta SHG) exhibited increased infectivity but had little effect on MDDC maturation. However, MDDC stimulated with Delta SHG induced increased proliferation of autologous Th1-polarized CD4(+) T cells. This effect was independent of virus replication. Increased T cell proliferation was strictly dependent on contact between virus-stimulated MDDC and CD4(+) T cells. Confocal microscopy revealed that deletion of SH and G was associated with an increased number of immunological synapses between memory CD4(+) T cells and virus-stimulated MDDC. Uptake of HMPV by MDDC was found to be primarily by macropinocytosis. Uptake of wild-type (WT) virus was reduced compared to that of Delta SHG, indicative of inhibition by the SH and G glycoproteins. In addition, DC-SIGN-mediated endocytosis provided a minor alternative pathway that depended on SH and/or G and thus operated only for WT. Altogether, our results show that SH and G glycoproteins reduce the ability of HMPV to be internalized by MDDC, resulting in a reduced ability of the HMPV-stimulated MDDC to activate CD4(+) T cells. This study describes a previously unknown mechanism of virus immune evasion. C1 [Le Nouen, Cyril; Brock, Linda G.; Winter, Christine C.; Collins, Peter L.; Buchholz, Ursula J.] NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Hillyer, Philippa; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Le Nouen, C (reprint author), NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lenouenc@niaid.nih.gov FU Intramural Research Program of the NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 9 Z9 9 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2014 VL 88 IS 11 BP 6453 EP 6469 DI 10.1128/JVI.03261-13 PG 17 WC Virology SC Virology GA AH2SB UT WOS:000335970300050 PM 24672038 ER PT J AU Givens, CE Bowers, JC DePaola, A Hollibaugh, JT Jones, JL AF Givens, C. E. Bowers, J. C. DePaola, A. Hollibaugh, J. T. Jones, J. L. TI Occurrence and distribution of Vibrio vulnificus and Vibrio parahaemolyticus - potential roles for fish, oyster, sediment and water SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article DE environmental; fish (live); water; shellfish; sediment ID GULF-OF-MEXICO; TIME PCR ASSAY; RIBOSOMAL-RNA; NORTHERN GULF; UNITED-STATES; CHESAPEAKE BAY; COAST; DIFFERENTIATION; TEMPERATURE; DENSITIES AB Vibrio vulnificus and Vibrio parahaemolyticus are Gram-negative marine bacteria naturally found in estuaries such as the Gulf of Mexico and can be pathogenic to humans. We quantified both of these organisms in fish, oyster, sediment, and water using culture-independent (quantitative PCR; qPCR) and culture-dependent (direct plating-colony hybridization; DP-CH) techniques during the transition period between winter and spring. We correlated these levels to environmental conditions and to abundance of total bacteria and total vibrio. By qPCR, fish intestine samples had the highest V.vulnificus densities and were 2 center dot 7, 3 center dot 5, and 4 center dot 2 logs greater than oyster, sediment and water samples, respectively. Densities of V.parahaemolyticus in fish samples by qPCR were 1 center dot 0, 2 center dot 1, and 3 center dot 1 logs greater than oyster, sediment and water samples, respectively. Similar differences between sample types were also observed by DP-CH. The difference between the more favourable and less favourable environmental conditions identified in this study was small (mean salinity 4 center dot 3 vs. 13ppt). However, V.vulnificus and V.parahaemolyticus were consistently detected in fish intestines, but infrequently detected and at lower levels in oysters and during the less favourable period. This trend was observed by qPCR and DP-CH, indicating fish intestines are a significant source of pathogenic vibrios in the environment. Significance and Impact of the Study This is the first study to report the densities of Bacteria 16S rRNA, Vibrio 16S rRNA, Vibrio vulnificus, and V.parahaemolyticus in fish intestine, oyster, sediment and water samples, as well as compare these values through culture-dependent and culture-independent methodology. Vibrio vulnificus and V.parahaemolyticus were detected in samples of fish intestines by qPCR and colony hybridization when conditions were less favourable for their occurrence in the environment. In contrast, V.vulnificus and V.parahaemolyticus were infrequently detected and at lower levels in other niches examined. These results indicate that fish intestinal tracts are a significant source of these pathogens. C1 [Givens, C. E.; Hollibaugh, J. T.] Univ Georgia, Dept Marine Sci, Athens, GA 30602 USA. [Bowers, J. C.] US FDA, Div Publ Hlth Informat & Analyt, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [DePaola, A.; Jones, J. L.] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. RP Jones, JL (reprint author), 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM Jessica.Jones@fda.hhs.gov FU NOAA Oceans and Human Health Initiative Traineeship [S0867882] FX This research was primarily supported by NOAA Oceans and Human Health Initiative Traineeship S0867882. We thank Catharina Ludeke, Ronald A. Benner, Jr., Tony Previto, George Doup, Jeff Krantz, Kevin Calci, Chris Lott, Kristin Butler, and Erin Lipp for their assistance and advice. NR 39 TC 16 Z9 16 U1 2 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0266-8254 EI 1472-765X J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD JUN PY 2014 VL 58 IS 6 BP 503 EP 510 DI 10.1111/lam.12226 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA AH2WE UT WOS:000335981900001 PM 24571291 ER PT J AU Hunsinger, M Smith, SM McKeown, A Parkhurst, M Gross, RA Lin, AH McDermott, MP Rappaport, BA Turk, DC Dworkin, RH AF Hunsinger, Matthew Smith, Shannon M. McKeown, Andrew Parkhurst, Melissa Gross, Robert A. Lin, Allison H. McDermott, Michael P. Rappaport, Bob A. Turk, Dennis C. Dworkin, Robert H. TI Disclosure of authorship contributions in analgesic clinical trials and related publications: ACTTION systematic review and recommendations SO PAIN LA English DT Review ID GHOST AUTHORSHIP; INDUSTRY DOCUMENTS; MEDICAL JOURNALS; HONORARY; POLICIES; PREVALENCE; STATEMENTS; GUIDELINES; ARTICLES; CRITERIA C1 [Smith, Shannon M.; McKeown, Andrew] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY USA. [Parkhurst, Melissa] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY USA. [Gross, Robert A.; McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Lin, Allison H.; Rappaport, Bob A.] US FDA, Silver Spring, MD USA. [McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Dworkin, Robert H.] Univ Washington, Dept Anesthesiol & Neurol, Sch Med & Dent, Seattle, WA 98195 USA. [Dworkin, Robert H.] Univ Washington, Ctr Human Expt Therapeut, Sch Med & Dent, Seattle, WA 98195 USA. [Hunsinger, Matthew] Univ Pacific, Sch Profess Psychol, Hillsboro, OR 97124 USA. RP Hunsinger, M (reprint author), Univ Pacific, Sch Profess Psychol, Hillsboro, OR 97124 USA. EM matthewh@pacificu.edu FU ACTTION public-private partnership; U.S. Food and Drug Administration (FDA) FX The authors thank Donna Berryman, MLIS, and Michele Shipley, MLS (University of Rochester Medical Center, Miner Library), for their help identifying articles for this study, and Mark P. Jensen, PhD (University of Washington), for valuable discussions that clarified our thinking. Financial support for this project was provided by the ACTTION public-private partnership with the U.S. Food and Drug Administration (FDA), which has received research Grants or other revenue from the FDA, various pharmaceutical companies, and other sources. NR 39 TC 1 Z9 1 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JUN PY 2014 VL 155 IS 6 BP 1059 EP 1063 DI 10.1016/j.pain.2013.12.011 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA AH1SY UT WOS:000335902500006 PM 24334187 ER PT J AU Chen, JJ Lu, TP Chen, DT Wang, SJ AF Chen, James J. Lu, Tzu-Pin Chen, Dung-Tsa Wang, Sue-Jane TI Biomarker adaptive designs in clinical trials SO TRANSLATIONAL CANCER RESEARCH LA English DT Review DE Adaptive signature design (ASD); classification; personalized medicine; predictive classifier; subgroup analysis; subgroup identification AB Predictive biomarkers are used to develop (binary) classifiers to identify patients as either good or poor candidates for clinical decision to optimize treatment selection. Ideally, these candidate biomarkers have been well studied in the phase II developmental stage, the performance characteristics of the classifier are well established in one or more retrospective validation, and the assay and predictive performance are reproducible and robust experimentally and analytically. However, completely phase II validated biomarkers for uses in phase III trial are often unavailable. Adaptive signature design (ASD) combines the biomarker identification and classifier development to the selection of candidate patients and a statistical test for treatment effect on the selected patient subgroup for phase III clinical trials. Biomarker-adaptive designs identify the most suitable target subpopulations, based on clinical observations or known biomarkers, and evaluate the effectiveness of the treatment on that subpopulation in a statistically valid manner. This review is concerned with statistical aspects in the biomarker adaptive design for randomized clinical trials. Statistical issues include the interaction test to identify predictive biomarkers, subgroup analysis, multiple testing and false discovery rate (FDR), classification of imbalanced class size data, sample size and power, and validation of the classification model. C1 [Chen, James J.; Lu, Tzu-Pin] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Lu, Tzu-Pin] Natl Taiwan Univ, YongLin Biomed Engn Ctr, Taipei 10764, Taiwan. [Chen, Dung-Tsa] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat & Bioinformat, Tampa, FL 33612 USA. [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Chen, JJ (reprint author), 3900 NCTR Rd,HFT 20, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov NR 73 TC 11 Z9 11 U1 0 U2 0 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2218-676X EI 2219-6803 J9 TRANSL CANCER RES JI Transl. Cancer Res. PD JUN PY 2014 VL 3 IS 3 BP 279 EP 292 DI 10.3978/j.issn.2218-676X.2014.05.04 PG 14 WC Oncology SC Oncology GA V42WK UT WOS:000209643700011 ER PT J AU Hirsch, DS Shen, Y Dokmanovic, M Yu, J Mohan, N Elzarrad, MK Wu, WJ AF Hirsch, Dianne S. Shen, Yi Dokmanovic, Milos Yu, Joyce Mohan, Nishant Elzarrad, Mohammed Khair Wu, Wen Jin TI Insulin activation of vacuolar protein sorting 34 mediates localized phosphatidylinositol 3-phosphate production at lamellipodia and activation of mTOR/S6K1 SO CELLULAR SIGNALLING LA English DT Article DE Class III phosphatidylinositol 3-kinase/vacuolar protein sorting 34 (VPS34); Insulin; Src; ptdins(3)p; S6 kinase 1 (S6K1); mTOR ID MAMMALIAN-CELLS; TYROSINE PHOSPHORYLATION; ACTIN CYTOSKELETON; S6 KINASE; 3-KINASE; RESISTANCE; MOTILITY; INSIGHTS; HVPS34; GROWTH AB The class III phosphatidylinositol 3-kinase, VPS34, phosphorylates the 03 hydroxyl of inositol generating phosphatidylinositol 3-phosphate (ptdins(3)p). Initial studies suggested that ptdins(3)p solely functioned as a component of vesicular and endosomal membranes and that VPS34 did not function in signal transduction. However, VPS34 has recently been shown to be required for insulin-mediated activation of S6 kinase 1 (S6K1). Whether VPS34 activity is directly regulated by insulin is unclear. It is also not known whether VPS34 activity can be spatially restricted in response to extracellular stimuli. Data presented here demonstrate that in response to insulin, VPS34 is activated and translocated to lamellipodia where it produces ptdins(3)p. The localized production of ptdins(3)p is dependent on Src phosphorylation of VPS34.1n cells expressing VPS34 with mutations at Y231 or Y310, which are Src-phosphorylation sites, insulin-stimulated VPS34 translocation to the plasma membrane and lamellipodia formation are blocked. mTOR also colocalizes with VPS34 and ptdins(3)p at lamellipodia following insulin-stimulation. In cells expressing the VPS34-Y231F mutant, which blocks lamellipodia formation, mTOR localization at the plasma membrane and insulin-mediated S6K1 activation are reduced. This suggests that mTOR localization at lamellipodia is important for full activation of S6K1 induced by insulin. These data demonstrate that insulin can spatially regulate VPS34 activity through Src-mediated tyrosine phosphorylation and that this membrane localized activity contributes to lamellipodia formation and activation of mTOR/S6K1signaling. Published by Elsevier Inc. C1 [Hirsch, Dianne S.; Shen, Yi; Dokmanovic, Milos; Yu, Joyce; Mohan, Nishant; Elzarrad, Mohammed Khair; Wu, Wen Jin] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Elzarrad, Mohammed Khair] NCI, Interagency Oncol Task Force IOTF Fellowship Prog, NIH, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, HFD 123,29B Lincoln Dr,Room 3NN20, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov NR 37 TC 3 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 EI 1873-3913 J9 CELL SIGNAL JI Cell. Signal. PD JUN PY 2014 VL 26 IS 6 BP 1258 EP 1268 DI 10.1016/j.cellsig.014.02.009 PG 11 WC Cell Biology SC Cell Biology GA AG0OH UT WOS:000335114300011 PM 24582588 ER PT J AU Lebrec, H Molinier, B Boverhof, D Collinge, M Freebern, W Henson, K Mytych, DT Ochs, HD Wange, R Yang, Y Zhou, L Arrington, J Christin-Piche, MS Shenton, J AF Lebrec, Herve Molinier, Brigitte Boverhof, Darrell Collinge, Mark Freebern, Wendy Henson, Kristin Mytych, Daniel T. Ochs, Hans D. Wange, Ronald Yang, Yung Zhou, Lei Arrington, Joshua Christin-Piche, Marie Soleil Shenton, Jacintha TI The T-cell-dependent antibody response assay in nonclinical studies of pharmaceuticals and chemicals: Study design, data analysis, interpretation SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE TDAR; Nonclinical studies; Immunotoxicity ID KEYHOLE-LIMPET HEMOCYANIN; HUMORAL IMMUNE-RESPONSE; IMMUNOTOXICOLOGICAL FUNCTIONAL ASSAY; SEVERE COMBINED IMMUNODEFICIENCY; HAZARD IDENTIFICATION PURPOSES; BONE-MARROW-TRANSPLANTATION; SCHISTOSOMA-MANSONI; IN-VIVO; BACTERIOPHAGE PHI-X-174; STANDARD TOXICOLOGY AB The T-cell-dependent antibody response (TDAR) assay is a measure of immune function that is dependent upon the effectiveness of multiple immune processes, including antigen uptake and presentation, T cell help, B cell activation, and antibody production. It is used for risk and safety assessments, in conjunction with other toxicologic assessments, by the chemical and pharmaceutical industries, and research and regulatory agencies. It is also employed to evaluate investigational drug efficacy in animal pharmacology studies, provide evidence of biological impact in clinical trials, and evaluate immune function in patients with primary or secondary immunodeficiency diseases. Various immunization schemes, analytical methods, approaches to data analysis, and data interpretations are in use. This manuscript summarizes some recommended practices for the conduct and interpretation of the assay in animal studies. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lebrec, Herve] Amgen Inc, Seattle, WA USA. [Molinier, Brigitte] Sanofi Aventis R&D, Montpellier, France. [Boverhof, Darrell] Dow Chem Co USA, Midland, MI 48674 USA. [Collinge, Mark] Pfizer Inc, Groton, CT 06340 USA. [Freebern, Wendy] Bristol Myers Squibb Co, New Brunswick, NJ USA. [Henson, Kristin] Novartis Inst Biomed Res Inc, E Hartford, NJ USA. [Mytych, Daniel T.] Amgen Inc, Thousand Oaks, CA USA. [Ochs, Hans D.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Ochs, Hans D.] Seattle Childrens Res Inst, Seattle, WA USA. [Wange, Ronald] Food & Drug Adm, Washington, DC USA. [Yang, Yung] US Environm Protect Agcy, Off Pesticides Programs, Washington, DC USA. [Arrington, Joshua] Covance Inc, Madison, WI USA. [Christin-Piche, Marie Soleil] Charles River Labs, Montreal, PQ, Canada. [Shenton, Jacintha] MedImmune Ltd, Cambridge, England. RP Lebrec, H (reprint author), Amgen Inc, 1201 Amgen Court West,AW1-J4144, Seattle, WA 98119 USA. EM hlebrec@amgen.com NR 90 TC 1 Z9 1 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 EI 1096-0295 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 2014 VL 69 IS 1 BP 7 EP 21 DI 10.1016/j.yrtph.2014.02.008 PG 15 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA AG0SL UT WOS:000335125800002 PM 24566336 ER PT J AU Mandal, B Roe, BE Fein, SB AF Mandal, Bidisha Roe, Brian E. Fein, Sara B. TI Work and breastfeeding decisions are jointly determined for higher socioeconomic status US mothers SO REVIEW OF ECONOMICS OF THE HOUSEHOLD LA English DT Article DE Breastfeeding; Elasticity; Employment; Postpartum; Duration; Intensity; Simultaneous model ID MATERNAL EMPLOYMENT; UNITED-STATES; TOBIT-MODEL; HEALTH; CHILDREN; LEAVE; WOMEN AB We study postpartum decisions about paid work and breastfeeding using a simultaneous equations model. For our sample of higher socioeconomic status mothers, we find a joint decision process for three sets of decisions modeled: work leave duration and duration of any, as well as of exclusive, breastfeeding, and daily work hours and daily breastfeedings at infant age 3 months. We find that returning to paid work 1 week earlier reduces any breastfeeding duration by about two-thirds of a week while extending breastfeeding by a week delays work participation by about one-third of a week. We find larger elasticities for decisions involving daily work hours and number of breastfeedings at 3 months than for work leave duration and any breastfeeding duration and the smallest elasticities for duration of exclusive breastfeeding and work leave. This marks the first study to find a joint decision-making process for postpartum work and breastfeeding decisions and suggests that, in addition to increased leave impacting breastfeeding behaviors, successful breastfeeding promotion policies can have nontrivial impacts on the US labor market. C1 [Mandal, Bidisha] Washington State Univ, Sch Econ Sci, Pullman, WA 99164 USA. [Roe, Brian E.] Ohio State Univ, Columbus, OH 43210 USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Mandal, B (reprint author), Washington State Univ, Sch Econ Sci, POB 646210,Hulbert 103F, Pullman, WA 99164 USA. EM bmandal@wsu.edu; roe.30@osu.edu; Sara.Fein@fda.hhs.gov RI Roe, Brian/A-7386-2009 OI Roe, Brian/0000-0003-4228-2889 NR 35 TC 4 Z9 4 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1569-5239 EI 1573-7152 J9 REV ECON HOUSEHOLD JI Rev. Econ. Househ. PD JUN PY 2014 VL 12 IS 2 BP 237 EP 257 DI 10.1007/s11150-012-9152-y PG 21 WC Economics SC Business & Economics GA AG4OD UT WOS:000335398700002 ER PT J AU Gu, Q Lantz-McPeak, S Rosas-Hernandez, H Cuevas, E Ali, SF Paule, MG Sarkar, S AF Gu, Qiang Lantz-McPeak, Susan Rosas-Hernandez, Hector Cuevas, Elvis Ali, Syed F. Paule, Merle G. Sarkar, Sumit TI In vitro detection of cytotoxicity using FluoroJade-C SO TOXICOLOGY IN VITRO LA English DT Article DE Toxicity; Cell culture; Fluorescence microscopy ID JADE-B; NEURONAL DEGENERATION; LOCALIZATION; ASTROCYTES; TOXICITY; CADMIUM; INJURY; MOUSE AB We describe here a novel method for the determination of cytotoxicity in cell cultures using Fluoro-Jade C (FJ-C). FJ-C has been previously used for the assessment of neurodegeneration in fixed brain tissue samples, and has never been utilized in live cell cultures or in different types of cells other than neurons. In the present study we examined the utility of FJ-C for the determination of cytotoxicity in vitro. Various cell cultures were evaluated including neural stem cells, brain microvessel endothelial cells, and SH-SY5Y, PC12 and MDCK cells. Cytotoxicities induced by toxicants in cell cultures, as determined by the FJ-C labeling, were further confirmed by commonly used cytotoxicity assays. This in vitro approach is simple, fast, and sensitive and, thus, has the potential to augment if not replace currently used cell-based cytotoxicity assays. Published by Elsevier Ltd. C1 [Gu, Qiang; Lantz-McPeak, Susan; Rosas-Hernandez, Hector; Cuevas, Elvis; Ali, Syed F.; Paule, Merle G.; Sarkar, Sumit] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gu, Q (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM qiang.gu@fda.hhs.gov RI Hector, Rosas-Hernandez/J-5130-2015; OI Rosas-Hernandez, Hector/0000-0002-2736-8302 FU U.S. Food and Drug Administration; National Center for Toxicological Research [E746001, E752401] FX This work was supported by the U.S. Food and Drug Administration, National Center for Toxicological Research, protocol numbers E746001 and E752401. The views expressed here are those of the authors and not necessarily those of the U.S. Food and Drug Administration. NR 19 TC 1 Z9 1 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD JUN PY 2014 VL 28 IS 4 BP 469 EP 472 DI 10.1016/j.tiv.2014.01.007 PG 4 WC Toxicology SC Toxicology GA AG3BA UT WOS:000335289600001 PM 24462471 ER PT J AU Bidzhieva, B Laassri, M Chumakov, K AF Bidzhieva, Bella Laassri, Majid Chumakov, Konstantin TI Allele-specific PCR for quantitative analysis of mutants in live viral vaccines SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Oral Polio Vaccine; Virulent revertants; Consistency monitoring; MAPREC; Alternative methods ID REAL-TIME PCR; PRIMER-TEMPLATE MISMATCHES; ORAL POLIOVIRUS VACCINE; VIRUS; REVERSION; MUTATION; SYSTEM; DNA; NEUROVIRULENCE; SAMPLES AB Monitoring consistency of genetic composition of oral polio vaccine (OPV) is a part of its quality control. It is performed by mutant analysis by PCR and restriction enzyme cleavage (MAPREC) used to quantify neurovirulent revertants in the viral genome. Here an alternative method based on quantitative PCR is proposed. Allele-specific quantitative polymerase chain reaction (asqPCR) uses a "tethered" oligonucleotide primer consisting of two specific parts connected by a polyinosine stretch. Homogeneous DNA from plasmids containing wild Leon/37 and attenuated Sabin 3 sequences with 100% 472(C) and 100% 472(T) could only be amplified using homologous primers. Real-time implementation of the allele-specific PCR resulted in sensitive detection of 472(C) revertants with the limit of quantitation of less than 0.05%. Monovalent vaccine batches and international viral references for MAPREC test were used to validate the method. asqPCR performed with the WHO references and monovalent batches of vaccine showed that the new method could measure accurately and reproducibly the content of revertants producing values comparable to MAPREC results. This suggests that asqPCR could be used as an alternative to MAPREC for lot release of OPV. The method could also be used for the quantitation of other mutants in populations of microorganisms. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). C1 [Bidzhieva, Bella; Laassri, Majid; Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. EM konstantin.chumakov@fda.hhs.gov NR 25 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 EI 1879-0984 J9 J VIROL METHODS JI J. Virol. Methods PD JUN 1 PY 2014 VL 201 BP 86 EP 92 DI 10.1016/j.jviromet.2014.02.012 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA AF8QA UT WOS:000334979500015 PM 24607431 ER PT J AU Mueller, GA Ankney, JA Glesner, J Khurana, T Edwards, LL Pedersen, LC Perera, L Slater, JE Pomes, A London, RE AF Mueller, Geoffrey A. Ankney, John A. Glesner, Jill Khurana, Taruna Edwards, Lori L. Pedersen, Lars C. Perera, Lalith Slater, Jay E. Pomes, Anna London, Robert E. TI Characterization of an anti-Bla g 1 scFv: Epitope mapping and cross-reactivity SO MOLECULAR IMMUNOLOGY LA English DT Article DE Allergen; Structure; Bla g 1; scFv; Cockroach; Epitope ID COCKROACH ALLERGEN BLA-G-2; INNER-CITY CHILDREN; MONOCLONAL-ANTIBODY; AMERICAN COCKROACH; HYDROGEN-EXCHANGE; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; EXPOSURE; BINDING; IGE AB Bla g 1 is a major allergen from Blatella germanica and one of the primary allergens used to assess cockroach allergen exposure. The epitope of an anti-Bla g 1 scEv was mapped in order to better understand cross reactivity with other group 1 cockroach allergens and patient IgE epitopes. X-ray crystallography was used to determine the structure of the scFv. The scEv epitope on Bla g 1 was located by alanine scanning sitedirected mutagenesis and ELISA. Twenty-six rBla g 1-GST alanine mutants were evaluated for variations in binding to the scFv compared to the wild type allergen. Six mutants showed a significant difference in scFv binding affinity. These mutations clustered to form a discontinuous epitope mainly comprising two helices of Bla g 1. The allergen-scFv complex was modeled based on the results, and the epitope region was found to have low sequence similarity with Per a 1, especially among the residues identified as functionally important for the scFy binding to Bla g I. Indeed, the scEv failed to bind Per a 1 in American cockroach extract. The scEv was unable to inhibit the binding of IgE antibodies from a highly cockroach allergic patient to Bla g 1. Based on the surface area of Bla g 1 occluded by the scFv, putative regions of patient IgE-Bla g 1 interactions can be inferred. This scFy could be best utilized as a capture antibody in an IgE detection ELISA, or to differentiate Bla g 1 from Per a 1 in environmental exposure assays. Published by Elsevier Ltd. C1 [Mueller, Geoffrey A.; Ankney, John A.; Edwards, Lori L.; Pedersen, Lars C.; Perera, Lalith; London, Robert E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Khurana, Taruna; Slater, Jay E.] US FDA, Bethesda, MD 20892 USA. [Glesner, Jill; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA 22903 USA. RP Mueller, GA (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM mueller3@niehs.nih.gov OI Pomes, Anna/0000-0002-8729-1829 FU Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health [Z01-ES102885-01, ZIA-ES102645]; National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01A1077653]; U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX This research was supported in part by Research Project Number Z01-ES102885-01 to REL, and ZIA-ES102645 to LCP in the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. Research reported in this publication was supported in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01A1077653 (PI: AP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. The authors thank Traci Hall and Andrea Moon for a critical reading of the manuscript. NR 37 TC 1 Z9 1 U1 0 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUN PY 2014 VL 59 IS 2 BP 200 EP 207 DI 10.1016/j.molimm.2014.02.003 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA AF8TP UT WOS:000334988800011 PM 24667070 ER PT J AU Son, I Binet, R Maounounen-Laasri, A Lin, A Hammack, TS Kase, JA AF Son, Insook Binet, Rachel Maounounen-Laasri, Anna Lin, Andrew Hammack, Thomas S. Kase, Julie A. TI Detection of five Shiga toxin-producing Escherichia coli genes with multiplex PCR SO FOOD MICROBIOLOGY LA English DT Article DE Escherichia coli; STEC; Multiplex PCR; Virulence ID HEMOLYTIC-UREMIC SYNDROME; NUCLEOTIDE-SEQUENCE; VIRULENCE FACTORS; SEROTYPE O157-H7; INTIMIN VARIANT; UNITED-STATES; IDENTIFICATION; STRAINS; CLONING; DISEASE AB Escherichia coli serogroup O157 is the pathogen most commonly associated with foodborne disease outbreaks, but epidemiological studies suggest that non-O157 Shiga toxin-producing E. coli (STEC) is a major player as well. The ten most clinically relevant STECs belong to serogroups O26, O103, O111, O145, O157, O91, O113, O128, O45, and O121; but emerging strains, such as O104:H4 that was identified with the 2011 German outbreak, could become more prevalent in the future. A 75-min conventional multiplex PCR assay, IS-5P, targeting the four virulence factors stx1, stx2, eae, and ehxA plus the O157:H7-specific +93 uidA single nucleotide polymorphism was developed to better assess the potential pathogenicity of STEC isolates. All 212 STEC DNAs showed one to five amplification products, while the non-E. coli DNA did not react to this multiplex PCR assay. Enrichment broths obtained from baby spinach, alfalfa sprouts, and cilantro artificially inoculated with O26, O103, and O121 STECs reacted positively to the multiplex assay. Unlike the current FDA BAM 5P PCR, designed for the specific detection of O157:H7, IS-5P will identify potentially harmful O157:H7 and non-O157 STECs so they can be removed from the nation's food supply. (C) 2013 Published by Elsevier C1 [Son, Insook; Binet, Rachel; Hammack, Thomas S.; Kase, Julie A.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Maounounen-Laasri, Anna] Oak Ridge Res Inst Sci & Educ, Oak Ridge, TN 37830 USA. [Lin, Andrew] US FDA, San Francisco Dist Lab, Alameda, CA 94502 USA. RP Son, I (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, Microbial Methods Dev Branch,Off Regulatory Sci, 5100 Paint Branch Pkwy,Mailstop HFS-711, College Pk, MD 20740 USA. EM insook.son@fda.hhs.gov; rachel.binet@fda.hhs.gov; anna.laasri@fda.hhs.gov; andrew.lin@fda.hhs.gov; thomas.hammack@fda.hhs.gov; julie.kase@fda.hhs.gov NR 54 TC 9 Z9 13 U1 0 U2 38 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2014 VL 40 BP 31 EP 40 DI 10.1016/j.fm.2013.11.016 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA AC8YQ UT WOS:000332821400005 PM 24549195 ER PT J AU Binet, R Deer, DM Uhlfelder, SJ AF Binet, Rachel Deer, Deanne M. Uhlfelder, Samantha J. TI Rapid detection of Shigella and enteroinvasive Escherichia coli in produce enrichments by a conventional multiplex PCR assay SO FOOD MICROBIOLOGY LA English DT Article DE Rapid detection; Shigella; Enteroinvasive Escherichia coli; Multiplex PCR; Fresh produce; DNA extraction ID REAL-TIME PCR; AMPLIFICATION; FOODS; PATHOGENS; SONNEI; SPP. AB Faster detection of contaminated foods can prevent adulterated foods from being consumed and minimize the risk of an outbreak of foodborne illness. A sensitive molecular detection method is especially important for Shigella because ingestion of as few as 10 of these bacterial pathogens can cause disease. The objectives of this study were to compare the ability of four DNA extraction methods to detect Shigella in six types of produce, post-enrichment, and to evaluate a new and rapid conventional multiplex assay that targets the Shigella ipaH, virB and mxiC virulence genes. This assay can detect less than two Shigella cells in pure culture, even when the pathogen is mixed with background microflora, and it can also differentiate natural Shigella strains from a control strain and eliminate false positive results due to accidental laboratory contamination. The four DNA extraction methods (boiling, PrepMan Ultra [Applied Biosystems], InstaGene Matrix [Bio-Rad], DNeasy Tissue kit [Qiagen]) detected 1.6 x 10(3) Shigella CFU/ml post-enrichment, requiring similar to 18 doublings to one cell in 25 g of produce pre-enrichment. Lower sensitivity was obtained, depending on produce type and extraction method. The InstaGene Matrix was the most consistent and sensitive and the multiplex assay accurately detected Shigella in less than 90 min, outperforming, to the best of our knowledge, molecular assays currently in place for this pathogen. Published by Elsevier Ltd. C1 [Binet, Rachel; Deer, Deanne M.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Uhlfelder, Samantha J.] Oak Ridge Res Inst Sci & Educ, Oak Ridge, TN 37830 USA. RP Binet, R (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM rachel.binet@fda.hhs.gov OI Binet, Rachel/0000-0002-2823-105X NR 28 TC 6 Z9 10 U1 6 U2 19 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2014 VL 40 BP 48 EP 54 DI 10.1016/j.fm.2013.12.001 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA AC8YQ UT WOS:000332821400007 PM 24549197 ER PT J AU Iha, MH Barbosa, CB Heck, AR Trucksess, MW AF Iha, Maria Helena Barbosa, Cynara Baltazar Heck, Analia Ribeiro Trucksess, Mary W. TI Aflatoxin M-1 and ochratoxin A in human milk in Ribeirao Preto-SP, Brazil SO FOOD CONTROL LA English DT Article DE Human milk; Aflatoxin M-1; Ochratoxin A ID BREAST-MILK; MOTHERS; CARCINOGENICITY; SAMPLES; ANKARA; TURKEY; RATS AB The objective of this study was to determine the extent of aflatoxin M-1 (AFM(1)) and ochratoxin A (OTA) contamination in human breast milk in the city of Ribeirao Preto, Sao Paulo State, Brazil. During 2012, 100 samples of human milk were collected at the local Human Milk Bank. The method comprised, immunoaffinity column purification and isolation, liquid chromatography separation and fluorescence detection. The average percentage recoveries of AFM(1) and OTA spiked at 20 and 50 ng/L. in control human milk were 78.1 +/- 11.7% and 73.7 +/- 9.6%, respectively. The average relative standard deviations of AFM(1) and OTA spiked at the same levels were 11.7 and 9.6% respectively. The limits of detection was 0.3 ng/L for AFM(1) and OTA. The limit of determination was 0.8 ng/L for both mycotoxins. This method was used to analyze 100 human milk samples, of which, two samples were found to contain AFM(1), at level greater than 0.3 ng/L. OTA was detected in 66 samples (66%), wherein 32 were above the limit of detection and 34 were in the range of from 0.8 to 21 ng/L Results of our study indicate that breast-fed Brazilian infants had only an insignificant exposure to AFM(1) and OTA. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Iha, Maria Helena; Barbosa, Cynara Baltazar] Adolfo Lutz Inst, Ctr Lab Reg Ribeirao Preto, Nucleo Ciencias Quim & Bromatol, BR-14085410 Ribeirao Preto, SP, Brazil. [Heck, Analia Ribeiro] Banco de Leite Humano Hosp Clin Enfermeira Analia, Ribeirao Preto, SP, Brazil. [Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD USA. RP Iha, MH (reprint author), Adolfo Lutz Inst, Ctr Lab Reg Ribeirao Preto, Nucleo Ciencias Quim & Bromatol, Rua Minas 877, BR-14085410 Ribeirao Preto, SP, Brazil. EM mhiha@ial.sp.gov.br RI Iha, Maria/B-9428-2017 OI Iha, Maria/0000-0002-0222-2841 FU FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) FX The authors are grateful to FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) for financial support. NR 20 TC 12 Z9 12 U1 3 U2 33 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 EI 1873-7129 J9 FOOD CONTROL JI Food Control PD JUN PY 2014 VL 40 BP 310 EP 313 DI 10.1016/j.foodcont.2013.12.014 PG 4 WC Food Science & Technology SC Food Science & Technology GA AB3CW UT WOS:000331669900044 ER PT J AU Hu, ZL Patel, IR Mukherjee, A AF Hu, Zonglin Patel, Isha R. Mukherjee, Amit TI Genetic analysis of the roles of agaA, agaI, and agaS genes in the N-acetyl-D-galactosamine and D-galactosamine catabolic pathways in Escherichia coli strains O157:H7 and C (vol 13, 94, 2013) SO BMC MICROBIOLOGY LA English DT Correction C1 [Hu, Zonglin; Patel, Isha R.; Mukherjee, Amit] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Mukherjee, A (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM amit.mukherjee@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD MAY 30 PY 2014 VL 14 AR 127 DI 10.1186/1471-2180-14-127 PG 2 WC Microbiology SC Microbiology GA AK1DS UT WOS:000338156100001 ER PT J AU Endo, Y Blinova, K Romantseva, T Golding, H Zaitseva, M AF Endo, Yukinori Blinova, Ksenia Romantseva, Tatiana Golding, Hana Zaitseva, Marina TI Differences in PGE(2) Production between Primary Human Monocytes and Differentiated Macrophages: Role of IL-1 beta and TRIF/IRF3 SO PLOS ONE LA English DT Article ID NF-KAPPA-B; PATTERN-RECOGNITION RECEPTORS; FEBRILE RESPONSE; MOLECULAR-BIOLOGY; INTERFERON-BETA; GUINEA-PIGS; FEVER; ENDOTOXIN; CELLS; PROSTAGLANDIN AB Prostaglandin E2 (PGE(2)) is induced in vivo by bacterial products including TLR agonists. To determine whether PGE(2) is induced directly or via IL-1 beta, human monocytes and macrophages were cultured with LPS or with Pam3CSK4 in presence of caspase-1 inhibitor, ZVAD, or IL-1R antagonist, Kineret. TLR agonists induced PGE(2) in macrophages exclusively via IL-1 beta-independent mechanisms. In contrast, ZVAD and Kineret reduced PGE2 production in LPS-treated (but not in Pam3CSK4-treated) monocytes, by 30-60%. Recombinant human IL-1 beta augmented COX-2 and mPGES-1 mRNA and PGE(2) production in LPS-pretreated monocytes but not in un-primed or Pam3CSK4-primed monocytes. This difference was explained by the finding that LPS but not Pam3CSK4 induced phosphorylation of IRF3 in monocytes suggesting activation of the TRIF signaling pathway. Knocking down TRIF, TRAM, or IRF3 genes by siRNA inhibited IL-1 beta-induced COX-2 and mPGES-1 mRNA. Blocking of TLR4 endocytosis during LPS priming prevented the increase in PGE(2) production by exogenous IL-1 beta. Our data showed that TLR2 agonists induce PGE(2) in monocytes independently from IL-1 beta. In the case of TLR4, IL-1 beta augments PGE(2) production in LPS-primed monocytes (but not in macrophages) through a mechanism that requires TLR4 internalization and activation of the TRIF/IRF3 pathway. These findings suggest a key role for blood monocytes in the rapid onset of fever in animals and humans exposed to bacterial products and some novel adjuvants. C1 [Endo, Yukinori; Blinova, Ksenia; Romantseva, Tatiana; Golding, Hana; Zaitseva, Marina] US FDA, CBER, Bethesda, MD 20014 USA. RP Zaitseva, M (reprint author), US FDA, CBER, Bethesda, MD 20014 USA. EM marina.zaitseva@fda.hhs.gov FU Federal fund from the Critical Path Initiative at CBER; Federal fund from the Critical Path Initiative at FDA; Biomedical Advanced Research and Development Authority (BARDA), HHS FX This project has been funded in part with Federal funds from the Critical Path Initiative at CBER, FDA and from the Biomedical Advanced Research and Development Authority (BARDA), HHS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 5 Z9 6 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 28 PY 2014 VL 9 IS 5 AR e98517 DI 10.1371/journal.pone.0098517 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI4TS UT WOS:000336858300051 PM 24870145 ER PT J AU Weisz, A Ridge, CD Roque, JA Mazzola, EP Ito, Y AF Weisz, Adrian Ridge, Clark D. Roque, Jose A. Mazzola, Eugene P. Ito, Yoichiro TI Preparative separation of two subsidiary colors of FD&C Yellow No. 5 (Tartrazine) using spiral high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Spiral high-speed counter-current chromatography; Highly polar organic/high-ionic strength aqueous two-phase solvent systems; FD&C Yellow No. 5; Tartrazine; Subsidiary colors; NMR ID TUBING SUPPORT ROTOR; ACID-BASE EQUILIBRIA; QUINOLINE YELLOW; AZO-HYDRAZONE; PURIFICATION; COMPONENTS; SYSTEMS; DYES; SALT AB Specifications in the U.S. Code of Federal Regulations for the color additive FD&C Yellow No. 5 (Color Index No. 19140) limit the level of the tetrasodium salt of 4-[(4',5-disulfo[1,1'-biphenyl]-2-yl)hydrazono]-4,5-dihydro-5-oxo-1-(4-sulfophenyl)-1H-pyrazole-3-carboxylic acid and that of the trisodium salt of 4,4'-[4,5-dihydro-5-oxo-4-[(4-sulfophenyl)hydrazono]-1H-pyrazol-1,3-diyl]bis[benzenesulfonic acid], which are subsidiary colors abbreviated as Pk5 and Pk7, respectively. Small amounts of Pk5 and Pk7 are needed by the U.S. Food and Drug Administration for confirmatory analyses and for development of analytical methods. The present study describes the use of spiral high-speed counter-current chromatography (HSCCC) to separate the closely related minor components Pk5 and Pk7 from a sample of FD&C Yellow No. 5 containing similar to 3.5% Pk5 and similar to 0.7% Pk7. The separations were performed with highly polar organic/high-ionic strength aqueous two-phase solvent systems that were chosen by applying the recently introduced method known as graphic optimization of partition coefficients (Zeng et al., 2013). Multiple similar to 1.0 g portions of FD&C Yellow No. 5 (totaling 6.4g dye) were separated, using the upper phase of the solvent system 1-butanol/abs. ethanol/saturated ammonium sulfate/water, 1.7:0.3:1:1, v/v/v/v, as the mobile phase. After removing the ammonium sulfate from the HSCCC-collected fractions, these separations resulted in an enriched dye mixture (similar to 160 mg) of which Pk5 represented similar to 46% and Pk7, similar to 21%. Separation of the enriched mixture, this time using the lower phase of that solvent system as the mobile phase, resulted in 61 mg of Pk5 collected in fractions whose purity ranged from 88.0% to 92.7%. Pk7 (20.7 mg, similar to 83% purity) was recovered from the upper phase of the column contents. Application of this procedure also resulted in purifying the major component of FD&C Yellow No. 5 to >99% purity. The separated compounds were characterized by high-resolution mass spectrometry and several H-1 and C-13 nuclear magnetic resonance spectroscopic techniques. Published by Elsevier B.V. C1 [Weisz, Adrian; Roque, Jose A.] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ridge, Clark D.; Mazzola, Eugene P.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov FU Intramural NIH HHS [ZIA HL005107-06] NR 37 TC 7 Z9 7 U1 6 U2 34 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 EI 1873-3778 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAY 23 PY 2014 VL 1343 BP 91 EP 100 DI 10.1016/j.chroma.2014.03.059 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AH5UE UT WOS:000336195800012 PM 24755184 ER PT J AU Gannavaram, S Dey, R Avishe, K Selvapandiyan, A Salotra, P Nakhasi, HL AF Gannavaram, Sreenivas Dey, Ranadhir Avishe, Kumar Selvapandiyan, Angamuthu Salotra, Poonam Nakhasi, Hira L. TI Biomarkers of safety and immune protection for genetically modified live attenuated Leishmania vaccines against visceral leishmaniasis - discovery and implications SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE Leishmania; vaccine; genetically modified organisms; live attenuated parasites; vaccine-induced immunity; systems vaccinology; biomarkers of protection ID YELLOW-FEVER VACCINE; CUTANEOUS LEISHMANIASIS; SYSTEMS BIOLOGY; DNA VACCINATION; KALA-AZAR; DONOVANI INFECTION; INTERFERON-GAMMA; CROSS-PROTECTION; MALARIA VACCINE; PROTEIN UFM1 AB Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen(-/-) in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal individuals. In addition, comparative analysis of biomarkers in PBMCs from asymptomatic or healed visceral leishmaniasis individuals in response to vaccine candidates including live attenuated parasites may provide clues about determinants of protective immunity and be helpful in shaping the final Leishmania vaccine formulation in the clinical trials. C1 [Gannavaram, Sreenivas; Dey, Ranadhir; Nakhasi, Hira L.] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Avishe, Kumar; Salotra, Poonam] Indian Council Med Res, Natl Inst Pathol, New Delhi, India. [Selvapandiyan, Angamuthu] Inst Mol Med, New Delhi, India. RP Gannavaram, S (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM sreenivas.gannavaram@fda.hhs.gov; hira.nakhasi@fda.hhs.gov NR 93 TC 11 Z9 11 U1 1 U2 6 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD MAY 23 PY 2014 VL 5 AR 241 DI 10.3389/fimmu.2014.00241 PG 9 WC Immunology SC Immunology GA CH7NU UT WOS:000354224600002 PM 24904589 ER PT J AU Marks, PW AF Marks, Peter W. TI Update in Hematology and Oncology: Evidence Published in 2013 SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Marks, Peter W.] US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. RP Marks, PW (reprint author), US FDA, Ctr Biol Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM peter.marks@fda.hhs.gov NR 18 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 20 PY 2014 VL 160 IS 10 BP 712 EP 718 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA V44NX UT WOS:000209756800001 PM 24722624 ER PT J AU Beaver, JA Blumenthal, GM Hunter, NL Palmby, T Ibrahim, A Justice, RL Pazdur, R Cortazar, P AF Beaver, Julia A. Blumenthal, Gideon Michael Hunter, Nina L. Palmby, Todd Ibrahim, Amna Justice, Robert L. Pazdur, Richard Cortazar, Patricia TI Targeted therapy approvals: Summary and future directions. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 [Beaver, Julia A.; Blumenthal, Gideon Michael; Hunter, Nina L.; Palmby, Todd; Ibrahim, Amna; Justice, Robert L.; Pazdur, Richard; Cortazar, Patricia] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e22181 PG 2 WC Oncology SC Oncology GA CN7KL UT WOS:000358613201897 ER PT J AU Blumenthal, GM Karuri, S Khozin, S Kazandjian, D Zhang, H Zhang, LJ Tang, SH Sridhara, R Keegan, P Pazdur, R AF Blumenthal, Gideon Michael Karuri, Stella Khozin, Sean Kazandjian, Dickran Zhang, Hui Zhang, Lijun Tang, Shenghui Sridhara, Rajeshwari Keegan, Patricia Pazdur, Richard TI Overall response rate (ORR) as a potential surrogate for progression-free survival (PFS): A meta-analysis of metastatic non-small cell lung cancer (mNSCLC) trials submitted to the US Food and Drug Administration (FDA) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 [Blumenthal, Gideon Michael; Karuri, Stella; Khozin, Sean; Kazandjian, Dickran; Zhang, Hui; Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard] US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 8012 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613204077 ER PT J AU Hansen, AR Cook, N Ricci, MS Razak, ARA Le Tourneau, C McKeever, K Roskos, L Dixit, R Siu, LL Hinrichs, MJ AF Hansen, Aaron Richard Cook, Natalie Ricci, M. Stacey Razak, Albiruni R. A. Le Tourneau, Christophe McKeever, Kathleen Roskos, Lorin Dixit, Rakesh Siu, Lillian L. Hinrichs, Mary Jane TI Choice of starting dose for biopharmaceuticals in first-in-human phase I cancer clinical trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 Univ Toronto, Princess Margaret Canc Ctr, Univ Hlth Network, Div Med Oncol & Hematol, Toronto, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. US FDA, White Oak, MD USA. Off Oncol & Hematol Prod, Div Hematol & Oncol Toxicol, White Oak, MD USA. Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. Inst Curie, Dept Med Oncol, Paris, France. MedImmune LLC, Gaithersburg, MD USA. Translat Sci, Gaithersburg, MD USA. MedImmune, Gaithersburg, MD USA. MedImmune, Gaithersburg, MD USA. Princess Margaret Canc Ctr, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 2596 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202861 ER PT J AU Maher, VE Kacuba, A Ning, YMM Murgo, AJ Ibrahim, A Farrell, AT Keegan, P Justice, RL Pazdur, R AF Maher, Virginia Ellen Kacuba, Alice Ning, Yangmin M. Murgo, Anthony J. Ibrahim, Amna Farrell, Ann T. Keegan, Patricia Justice, Robert L. Pazdur, Richard TI Special protocol assessments: 10 years of experience in FDA's Office of Hematology and Oncology Produets SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 US FDA, Silver Spring, MD USA. NCI, US FDA, Silver Spring, MD USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e17511 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200971 ER PT J AU Ning, YMM Kim, T Maher, VE Ibrahim, A Murgo, AJ Farrell, AT Keegan, P Justice, RL Pazdur, R AF Ning, Yangmin M. Kim, Tamy Maher, Virginia Ellen Ibrahim, Amna Murgo, Anthony J. Farrell, Ann T. Keegan, Patricia Justice, Robert L. Pazdur, Richard TI FDA breakthrough therapy designation of oncology-products: The first-year experience. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, US FDA, Silver Spring, MD USA. US FDA, Rockville, MD 20857 USA. US FDA, Silver Spring, MD USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA e17502 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613200964 ER PT J AU Schrieber, SJ Zhao, H Keegan, P Booth, B Rahman, NA AF Schrieber, Sarah J. Zhao, Hong Keegan, Patricia Booth, Brian Rahman, Nam Atiqur TI Evaluation of the potential for QT/QTc interval prolongation for therapeutic biotechnology products. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2014 CL Chicago, IL SP Amer Soc Clin Oncol C1 [Schrieber, Sarah J.; Zhao, Hong; Keegan, Patricia; Booth, Brian; Rahman, Nam Atiqur] US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2014 VL 32 IS 15 SU S MA 2600 PG 1 WC Oncology SC Oncology GA CN7KL UT WOS:000358613202865 ER PT J AU Wang, JT Coburn, J Liang, CP Woolsey, N Ramella-Roman, JC Chen, Y Pfefer, TJ AF Wang, Jianting Coburn, James Liang, Chia-Pin Woolsey, Nicholas Ramella-Roman, Jessica C. Chen, Yu Pfefer, T. Joshua TI Three-dimensional printing of tissue phantoms for biophotonic imaging SO OPTICS LETTERS LA English DT Article ID OPTICAL-PROPERTIES; IN-VITRO AB We have investigated the potential of tissue phantoms fabricated with thermosoftening- and photopolymerization-based three-dimensional (3D) printers for use in evaluation of biophotonic imaging systems. The optical properties of printed polymer samples were measured and compared to biological tissues. Phantoms with subsurface channels as small as 0.2 mm in diameter were fabricated and imaged with microscopy, x-ray microtomography, and optical coherence tomography to characterize morphology. These phantoms were then implemented to evaluate the penetration depth of a hyperspectral reflectance imaging system used in conjunction with a near-infrared contrast agent. Results indicated that 3D printing may provide a suitable platform for performance testing in biophotonics, although subsurface imaging is critical to mitigate printer-to-printer variability in matrix homogeneity and feature microstructure. (C) 2014 Optical Society of America C1 [Wang, Jianting; Liang, Chia-Pin; Woolsey, Nicholas; Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Ramella-Roman, Jessica C.] Florida Int Univ, Dept Biomed Engn, Miami, FL 33174 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM joshua.pfefer@fda.hhs.gov FU National Science Foundation's FDA Scholar-in-Residence program (NSF) [CBET-1238407]; University of Maryland Center for Excellence in Regulatory Science and Innovation (CERSI) FX The authors acknowledge support from the National Science Foundation's FDA Scholar-in-Residence program (NSF, CBET-1238407) and the University of Maryland Center for Excellence in Regulatory Science and Innovation (CERSI). The authors would also like to thank Dr. Maureen Dreher for her help with micro-CT imaging. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 17 TC 18 Z9 18 U1 2 U2 31 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD MAY 15 PY 2014 VL 39 IS 10 BP 3010 EP 3013 DI 10.1364/OL.39.003010 PG 4 WC Optics SC Optics GA AI6KI UT WOS:000336982500048 PM 24978260 ER PT J AU Rathore, AS Kumar, V Arora, A Lute, S Brorson, K Shukla, A AF Rathore, Anurag S. Kumar, Vijesh Arora, Arushi Lute, Scott Brorson, Kurt Shukla, Anupam TI Mechanistic modeling of viral filtration SO JOURNAL OF MEMBRANE SCIENCE LA English DT Article DE Bacteriophage phi X-174; Viral retentive filters; LRV; Modeling; Viral clearance ID MURINE LEUKEMIA-VIRUS; MONOCLONAL-ANTIBODIES; MEMBRANE CAPACITY; PORE BLOCKAGE; CLEARANCE; MICROFILTRATION; CHROMATOGRAPHY; EXCLUSION; FILTER; PH AB A simple model based on changes in filter resistance and active area of the membrane has been used to model viral filtration. Viral particles have been modeled as colloidal particles disregarding any specific interaction and considering only passive transport in the system. The model is based on the assumption that purely steric interactions determine the ratio of concentration of viral particles inside the pore to concentration in solution at the pore mouth. Viral particles rejected by the membrane form a layer of high concentration near the membrane and this layer offers additional resistance to filtration. The membrane flux has been calculated by applying Darcy's law. The overall model involves use of six unknown parameters to account for cake formation, nature of virus, interaction between the virus and the membrane, and pore size. The breakthrough of the model virus, bacteriophage phi X-174, through normal-flow virus filters using commercial process fluids has been chosen as the system used for model validation. The model has been fitted to the time profile of flux and the log reduction value (LRV) of viral particles across the different types of commercially available filters. The model will be useful when performing studies using scale down models for correlating LRV to flux decline. The model also provides us insights into the underlying mechanisms behind viral clearance achieved from the various commercially available viral filters. (C) 2014 Elsevier B.V. All rights reserved. C1 [Rathore, Anurag S.; Kumar, Vijesh; Arora, Arushi; Shukla, Anupam] Indian Inst Technol, Dept Chem Engn, New Delhi 110016, India. [Lute, Scott; Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Silver Spring, MD 20903 USA. RP Rathore, AS (reprint author), Indian Inst Technol, Dept Chem Engn, New Delhi 110016, India. EM asrathore@biotechcmz.com NR 29 TC 2 Z9 2 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0376-7388 EI 1873-3123 J9 J MEMBRANE SCI JI J. Membr. Sci. PD MAY 15 PY 2014 VL 458 BP 96 EP 103 DI 10.1016/j.memsci.2014.01.037 PG 8 WC Engineering, Chemical; Polymer Science SC Engineering; Polymer Science GA AD7DG UT WOS:000333421200010 ER PT J AU Chan, DD Wu, KC Loring, Z Galeotti, L Gerstenblith, G Tomaselli, G Weiss, RG Wagner, GS Strauss, DG AF Chan, Dulciana D. Wu, Katherine C. Loring, Zak Galeotti, Loriano Gerstenblith, Gary Tomaselli, Gordon Weiss, Robert G. Wagner, Galen S. Strauss, David G. TI Comparison of the Relation Between Left Ventricular Anatomy and QRS Duration in Patients With Cardiomyopathy With Versus Without Left Bundle Braneh Block SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC RESYNCHRONIZATION THERAPY; MAGNETIC-RESONANCE; MYOCARDIAL SCAR; CONDUCTION; ACTIVATION; CRITERIA; HEART; MASS; STRICT; TISSUE AB QRS duration (QRSd) is used to diagnose left bundle branch block (LBBB) and is important to determine cardiac resynchronization therapy eligibility. The same QRSd thresholds established decades ago are used for all patients. However, significant interpatient variability of normal QRSd exists, and individualized QRSd thresholds might improve diagnosis and intervention strategies. Previous work reported left ventricular (LV) mass and papillary muscle location predicted QRSd in healthy subjects, but the relation in diseased ventricles is unknown. The aim of the present study was to determine the association between LV anatomy and QRSd in patients with cardiomyopathy. Patients referred for primary prevention implantable defibrillators (n = 166) received cardiac magnetic resonance imaging, and those with normal conduction (without bundle branch or fascicular block) and LBBB were studied. The LV mass, length, internal diameter, LV enddiastolic volume, septal and lateral wall thicknesses, and papillary muscle location were measured. In patients with normal conduction, LV length (r = 0.35, p <0.001), mass (r = 0.32, p <0.001), diameter (r = 0.20, p = 0.03), and septal wall thickness (r = 0.20, p = 0.03) had positive correlations with QRSd. In patients with LBBB, LV length (r = 0.32, p = 0.03), mass (r = 0.39, p = 0.01), diameter (r = 0.34, p = 0.02), and LV end-diastolic volume (r = 0.32, p = 0.04) had positive correlations with QRSd. Contrary to previous studies in healthy subjects, papillary muscle angle (location) was not associated with QRSd in cardiomyopathy patients with normal conduction or LBBB. In conclusion, increasing LV anatomical measurements were associated with increasing QRSd in patients with cardiomyopathy. Future work should investigate the use of LV anatomical measurements in developing individualized QRSd thresholds for diagnosing conduction abnormalities such as LBBB and identifying candidates for cardiac resynchronization therapy. Published by Elsevier Inc. C1 [Chan, Dulciana D.; Galeotti, Loriano; Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Wu, Katherine C.; Gerstenblith, Gary; Tomaselli, Gordon; Weiss, Robert G.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Loring, Zak] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA. [Wagner, Galen S.] Duke Univ, Med Ctr, Dept Internal Med, Durham, NC 27710 USA. RP Strauss, DG (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM david.strauss@fda.hhs.gov FU National Heart, Lung, and Blood Institute, National Institutes of Health [HL103812]; FDA's Critical Path Initiative; Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy FX The present study was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, HL103812 to Dr. Wu. This project was supported in part by FDA's Critical Path Initiative and appointments to the Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. NR 24 TC 4 Z9 5 U1 0 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2014 VL 113 IS 10 BP 1717 EP 1722 DI 10.1016/j.amjcard.2014.02.026 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH7UA UT WOS:000336339600021 PM 24698465 ER PT J AU Lim, JK Tate, JP Fultz, SL Goulet, JL Conigliaro, J Bryant, KJ Gordon, AJ Gibert, C Rimland, D Goetz, MB Klein, MB Fiellin, DA Justice, AC Lo Re, V AF Lim, Joseph K. Tate, Janet P. Fultz, Shawn L. Goulet, Joseph L. Conigliaro, Joseph Bryant, Kendall J. Gordon, Adam J. Gibert, Cynthia Rimland, David Goetz, Matthew Bidwell Klein, Marina B. Fiellin, David A. Justice, Amy C. Lo Re, Vincent, III TI Relationship Between Alcohol Use Categories and Noninvasive Markers of Advanced Hepatic Fibrosis in HIV-Infected, Chronic Hepatitis C Virus-Infected, and Uninfected Patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE alcohol; liver fibrosis; HIV; hepatitis C; FIB-4 ID VETERANS AGING COHORT; PLATELET RATIO INDEX; PREDICTING LIVER FIBROSIS; SUBSTANCE USE DISORDERS; ASPARTATE-AMINOTRANSFERASE; PSYCHIATRIC-DIAGNOSIS; SAMPLING VARIABILITY; CIRRHOSIS; VALIDATION; TESTS AB Background. It is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status. Methods. We performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous drinking, hazardous/binge drinking, or alcohol-related diagnosis. Advanced hepatic fibrosis was defined by FIB-4 index >3.25. Results. Within each HIV/HCV group, the prevalence of advanced hepatic fibrosis increased as alcohol use category increased. For each alcohol use category, advanced hepatic fibrosis was more common among HIV-infected than uninfected (nonhazardous: 6.7% vs 1.4%; hazardous/binge: 9.5% vs 3.0%; alcohol-related diagnosis: 19.0% vs 8.6%; P < .01) and chronic HCV-infected than uninfected (nonhazardous: 13.6% vs 2.5%; hazardous/binge: 18.2% vs 3.1%; alcohol-related diagnosis: 22.1% vs 6.5%; P < .01) participants. Strong associations with advanced hepatic fibrosis (adjusted odds ratio [95% confidence interval]) were observed among HIV/HCV-coinfected patients with nonhazardous drinking (14.2 [5.91-34.0]), hazardous/binge drinking (18.9 [7.98-44.8]), and alcohol-related diagnoses (25.2 [10.6-59.7]) compared with uninfected nonhazardous drinkers. Conclusions. Advanced hepatic fibrosis was present at low levels of alcohol consumption, increased with higher alcohol use categories, and was more prevalent among HIV-infected and chronic HCV-infected patients than uninfected individuals. All alcohol use categories were strongly associated with advanced hepatic fibrosis in HIV/HCV-coinfected patients. C1 [Lim, Joseph K.; Tate, Janet P.; Goulet, Joseph L.; Justice, Amy C.] Vet Affairs VA Connecticut Healthcare Syst, West Haven, CT USA. [Lim, Joseph K.; Tate, Janet P.; Goulet, Joseph L.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Fultz, Shawn L.] US FDA, Ctr Tobacco Prod, Washington, DC 20204 USA. Hofstra North Shore LIJ Sch Med, Lake Success, NY USA. [Conigliaro, Joseph] North Shore LIJ Hlth Syst, Lake Success, NY USA. [Bryant, Kendall J.] NIAAA, Bethesda, MD USA. [Gordon, Adam J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Gordon, Adam J.] Pittsburgh VA Med Ctr, Pittsburgh, PA USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Klein, Marina B.] McGill Univ, Ctr Hlth, Chron Viral Illness Serv, Montreal, PQ, Canada. [Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Publ Hlth, Yale Ctr Interdisciplinary Res AIDS, New Haven, CT USA. [Lo Re, Vincent, III] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Lo Re, V (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Lo Re, Vincent/N-7817-2015; OI Goetz, Matthew/0000-0003-4542-992X; Fiellin, David/0000-0002-4006-010X; Goulet, Joseph/0000-0002-0842-804X FU National Institute on Alcohol Abuse and Alcoholism [U01 AA13566, R21 AA015894]; National Institute of Allergy and Infectious Diseases [K01 AI070001] FX This study was supported by the National Institute on Alcohol Abuse and Alcoholism (grant numbers U01 AA13566 to A. C. J. and R21 AA015894 to J. K. L and A. C. J.) and the National Institute of Allergy and Infectious Diseases (grant number K01 AI070001 to V. L. R.). NR 60 TC 15 Z9 15 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2014 VL 58 IS 10 BP 1449 EP 1458 DI 10.1093/cid/ciu097 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AH3RZ UT WOS:000336044200020 PM 24569533 ER PT J AU Chenna, V Hu, CX Khan, SR AF Chenna, Venugopal Hu, Chaoxin Khan, Saeed R. TI Synthesis and cytotoxicity studies of Hedgehog enzyme inhibitors SANT-1 and GANT-61 as anticancer agents SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING LA English DT Article DE imine formation; GANT-61; SANT-1; Wills-Meyer-Hack reaction; N-arylation; Hedgehog pathway ID SMALL-MOLECULE INHIBITOR; PANCREATIC-CANCER; SIGNALING PATHWAY; PROSTATE-CANCER; BLOCKADE; GROWTH; GLI; ANTAGONIST; ACTIVATION AB Cancer-related death is one of the most common causes of mortality in society. Small molecules have the capability to disrupt aberrant signaling pathways in tumors, leading to anticancer activities. Therefore the search for new molecules for cancer treatment continues to draw attention to the scientific research community. Synthesis and biological evaluation of hedgehog (Hh) pathway inhibitors SANT-1 and GANT-61 are disclosed. These molecules have been synthesized from common precursors using simple conversions, our synthesis features Vils-Meier-Haack reaction, imine formation reaction and N-arylation reaction. These drugs were evaluated using a Hh reporter assay to confirm pathway inhibitory activity, and tested for cell viability against pancreatic and prostate cancer cells. These methodologies can be applied to make potent analogs of both inhibitors. C1 [Chenna, Venugopal; Hu, Chaoxin] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Chenna, Venugopal; Hu, Chaoxin] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Khan, Saeed R.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Khan, Saeed R.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Khan, SR (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM saeed.khan2@fda.hhs.gov FU Flight Attendant Medical Research Institute [FAMRI 062563_CIA] FX The authors thank Flight Attendant Medical Research Institute grant (FAMRI 062563_CIA) for the financial support. NR 37 TC 3 Z9 3 U1 0 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1093-4529 EI 1532-4117 J9 J ENVIRON SCI HEAL A JI J. Environ. Sci. Health Part A-Toxic/Hazard. Subst. Environ. Eng. PD MAY 12 PY 2014 VL 49 IS 6 BP 641 EP 647 DI 10.1080/10934529.2014.865425 PG 7 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA AB2CX UT WOS:000331601700004 PM 24521409 ER PT J AU Orleans, RJ Li, L Kim, MJ Guo, J Sobhan, M Soule, L Joffe, HV AF Orleans, Ronald J. Li, Li Kim, Myong-Jin Guo, Jia Sobhan, Mahboob Soule, Lisa Joffe, Hylton V. TI FDA Approval of Paroxetine for Menopausal Hot Flushes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; TAMOXIFEN; ESTROGEN; CYP2D6 AB An FDA advisory committee recommended against approving paroxetine for menopausal vasomotor symptoms. But recognizing the lack of hormone-free products for this indication, and after reviewing the drug's efficacy and safety, the FDA decided it can benefit some women. The recent approval by the Food and Drug Administration (FDA) of paroxetine (Brisdelle, Noven) for the treatment of moderate-to-severe vasomotor symptoms associated with menopause was distinctive for at least two reasons. First, it offered the first nonhormonal option to women who cannot or do not want to use hormonal medications to treat their menopausal vasomotor symptoms. Second, the approval ran counter to the recommendation of the FDA Reproductive Health Drugs Advisory Committee, which had concluded, by a vote of 10 to 4, that the overall benefit-risk profile of Brisdelle did not support approval. The FDA always carefully considers the advice ... C1 [Orleans, Ronald J.; Li, Li; Kim, Myong-Jin; Guo, Jia; Sobhan, Mahboob; Soule, Lisa; Joffe, Hylton V.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Orleans, RJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 5 TC 14 Z9 17 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 8 PY 2014 VL 370 IS 19 BP 1777 EP 1779 DI 10.1056/NEJMp1402080 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AH3CD UT WOS:000335997900004 PM 24806158 ER PT J AU Donaldson, FE Coburn, JC Siegel, KL AF Donaldson, Finn E. Coburn, James C. Siegel, Karen Lohmann TI Total hip arthroplasty head-neck contact mechanics: A stochastic investigation of key parameters SO JOURNAL OF BIOMECHANICS LA English DT Article DE Total hip arthroplasty; Wear; Trunnionosis; Modularity; Finite element analysis ID FRETTING CORROSION; FEMORAL-HEAD; CREVICE CORROSION; MORSE TAPER; MICROMOTION; PROSTHESIS; INTERFACE; STRENGTH; IMPLANTS; FAILURE AB A variety of design and patient parameters have been implicated in recent reports of fretting corrosion at modular connections in total hip arthroplasty. We sought to identify the relative sensitivity of mechanical fretting to a comprehensive set of parameters such that attention may be focused on key variables. Stochastic finite element simulation of the head-neck taper-trunnion junction was performed. Four-hundred parameter sets were simulated using realistic variations of design variables, material properties and loading parameters to predict contact pressures (P), micromotions (M) and fretting work (coefficient of friction x P x M) over cycles of gait. Results indicated that fretting work was correlated with only three parameters: angular mismatch, center offset and body weight (r= 0.47, 0.53 and 0.43, p < 0.001). Maximum contact pressure increased by 85 MPa for every 0.1 degrees of angular mismatch. Maximum micromotion increased by 5 gm per 10 mm additional head offset and 1 mu m per 10 kg increased body weight. Uncorrelated parameters included trunnion diameter, trunnion length and impaction forces. It was concluded that appropriate limiting of angular mismatch and center offset could minimize fretting, and hence its contribution to corrosion, at modular connections. Published by Elsevier Ltd. C1 [Donaldson, Finn E.; Coburn, James C.; Siegel, Karen Lohmann] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth,Off Med Prod & Tobacco, Silver Spring, MD 20993 USA. RP Donaldson, FE (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Room 1202 A,Bldg 62,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Finn.Donaldson@fda.hhs.gov OI Siegel, Karen Lohmann/0000-0002-0788-6612 FU Center for Devices and Radiological Health, FDA FX The authors would like to acknowledge the Critical Path Initiative from the Center for Devices and Radiological Health, FDA for funding this work. NR 34 TC 15 Z9 15 U1 1 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 EI 1873-2380 J9 J BIOMECH JI J. Biomech. PD MAY 7 PY 2014 VL 47 IS 7 BP 1634 EP 1641 DI 10.1016/j.jbiomech.2014.02.035 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA AI6VY UT WOS:000337016300011 PM 24657104 ER PT J AU Zhang, K Wong, JW Mai, H Trucksess, MW AF Zhang, Kai Wong, Jon W. Mai, Huy Trucksess, Mary W. TI Dopant-Assisted Atmospheric Pressure Photoionization of Patulin in Apple Juice and Apple-Based Food with Liquid Chromatography-Tandem Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE patulin; apple juice; APPI; dopant-assisted; stable isotope dilution; LC-MS/MS ID ISOTOPE DILUTION ASSAY; ELECTROSPRAY-IONIZATION; MYCOTOXINS; LC/MS; MILK; MS AB A dopant-assisted atmospheric pressure photoionization (APPI) with liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to determine patulin in apple juice and apple-based food. Different dopants, dopant flow rates, and LC separation conditions were evaluated. Using toluene as the dopant, the LC-APPI-MS/MS method achieved a linear calibration from 12.5 to 2000 mu g/L (r(2) > 0.99). Matrix-dependent limits of quantitation (LOQs) were from 8 mu g/L (solvent) to 12 mu g/L (apple juice). [C-13]-Patulin-fortified apple juice samples were directly analyzed by the LC-APPI-MS/MS method. Other apple-based food was fortified with [C-13]-patulin, diluted using water (1% formic acid), centrifuged, and filtered, followed by LC-APPI-MS/MS analysis. In clear apple juice, unfiltered apple cider, applesauce, and apple-based baby food, average recoveries were 101 +/- 6% (50 mu g/kg), 103 +/- 5% (250 mu g/kg), and 102 +/- 5% (1000 mu g/kg) (av +/- SD, n = 16). Using the suggested method, patulin was detected in 3 of 30 collected market samples with concentrations ranging from 298.1>268.0 and m/z 329.2>268.2>238.0 to detect AA I and II, respectively. The extraction and clean-up of target analytes from dry powdered samples was performed using the quick, easy, cheap, effective, rugged and safe (QuEChERS) procedure. Herbal liquid extracts were analysed directly. Average recoveries ranged from 89% to 112%, with relative standard deviations (RSDs) ranging from 3% to 16%. Limits of quantification (LOQs) estimated for three selected matrices were as follows (AA I/II): 5/10ngg(-1) (tablets); 25/50ngg(-1) (capsules); and 2.5/5.0ngml(-l) (liquid herbal extract). The method was applied in a limited survey of 30 herbal products marketed in the United States via the Internet. AA I and II were detected in 20% and 7%, respectively, of tested samples. C1 [Vaclavik, Lukas; Krynitsky, Alexander J.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Vaclavik, L (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM Lukas.Vaclavik@fda.hhs.gov FU US Department of Energy; US Food and Drug Administration FX L. V. acknowledges the support of an appointment to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. NR 28 TC 7 Z9 7 U1 2 U2 18 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 EI 1944-0057 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PD MAY 4 PY 2014 VL 31 IS 5 BP 784 EP 791 DI 10.1080/19440049.2014.892215 PG 8 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA AH1AK UT WOS:000335851700003 PM 24512293 ER PT J AU Zhao, YD Rahardja, D Wang, DH Shen, HL AF Zhao, Yan D. Rahardja, Dewi Wang, De-Hui Shen, Haili TI Testing Homogeneity of Stratum Effects in Stratified Paired Binary Data SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Paired binary data; Symmetry; McNemar's test; Bowker's test; Marginal homogeneity; Stratified test; Stuart-Maxwell test ID CLASSIFICATION AB For paired binary data, McNemar's test is widely used to test marginal homogeneity or symmetry for a 2 by 2 contingency table. In this article, we extend McNemar's test by considering a series of paired binary data in which the series is defined by a stratification factor. We provide a test for testing homogeneous stratum effects. For illustration, we apply our test to a cancer epidemiology study. Finally, we conduct simulations to show that our test preserves the nominal type I error level and evaluate the power of our test under various scenarios. C1 [Zhao, Yan D.] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA. [Rahardja, Dewi] US FDA, Silver Spring, MD USA. [Wang, De-Hui] Jilin Univ, Coll Math, Changchun 130023, Jilin, Peoples R China. RP Shen, HL (reprint author), Lanzhou Univ, Hosp 2, Dept Pain, Lanzhou 730030, Gansu, Peoples R China. EM shenhl@lzu.edu.cn NR 6 TC 2 Z9 2 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD MAY 4 PY 2014 VL 24 IS 3 BP 600 EP 607 DI 10.1080/10543406.2014.888440 PG 8 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA AE9NN UT WOS:000334334600009 PM 24697196 ER PT J AU Kornele, ML McLean, MJ O'Brien, AE Phillippi-Taylor, AM AF Kornele, Michelle L. McLean, Melanie J. O'Brien, Anna E. Phillippi-Taylor, Aimee M. TI Antiparasitic resistance and grazing livestock in the United States SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material ID ANTHELMINTIC RESISTANCE C1 [Kornele, Michelle L.; McLean, Melanie J.; O'Brien, Anna E.; Phillippi-Taylor, Aimee M.] US FDA, Ctr Vet Med, Antiparasit Resistance Management Strategy Grp, Rockville, MD 20855 USA. [Kornele, Michelle L.; O'Brien, Anna E.] US FDA, Ctr Vet Med, Div Therapeut Drugs Food Anim, Rockville, MD 20855 USA. [Phillippi-Taylor, Aimee M.] US FDA, Ctr Vet Med, Div Therapeut Drugs Nonfood Anim, Rockville, MD 20855 USA. [McLean, Melanie J.] US FDA, Ctr Vet Med, Off Director, Rockville, MD 20855 USA. RP O'Brien, AE (reprint author), US FDA, Ctr Vet Med, Antiparasit Resistance Management Strategy Grp, 7500 Standish Pl, Rockville, MD 20855 USA. EM anna.obrien@fda.hhs.gov NR 10 TC 1 Z9 1 U1 2 U2 7 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 EI 1943-569X J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD MAY 1 PY 2014 VL 244 IS 9 BP 1020 EP 1022 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA CA6BZ UT WOS:000348994700023 PM 24739108 ER PT J AU Schwerin, MR Walsh, DL Zhang, ZW AF Schwerin, Matthew R. Walsh, Donna L. Zhang, Zhiwei TI Effect of Isopropanol and Ethanol on the Tensile Properties of Natural Rubber Latex Condoms SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE condom; tensile strength; elongation; alcohol; isopropanol; ethanol; IPA AB The use of isopropanol as a means to remove lubricants from natural rubber latex (NRL) condoms prior to tensile testing is considered acceptable per ASTM D3492-08. However, there is some indication in the technical literature that isopropanol may be detrimental to NRL. In this study, three different brands of NRL condoms were tested for tensile properties after exposure to either isopropanol or one of two different ethyl alcohols, and a control group was tested without exposure to any alcohol. Tensile rings cut from NRL condoms were soaked in the respective alcohols for one hour at 25 degrees C and 50 % relative humidity before undergoing tensile testing. The results of this study are presented along with statistical analysis of the data (thickness, force at break, tensile strength, and elongation). Although the analysis shows there were a few statistically significant differences in some of the measured parameters, the differences were relatively small in magnitude and likely of minimal scientific importance. Consequently, we conclude that under the conditions used in this study, the alcohols tested do not have a detrimental effect on the tensile properties of NRL condoms. C1 [Schwerin, Matthew R.; Walsh, Donna L.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Solid & Fluid Mech, Silver Spring, MD 20993 USA. [Zhang, Zhiwei] US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, Silver Spring, MD 20993 USA. RP Schwerin, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Solid & Fluid Mech, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Matthew.Schwerin@fda.hhs.gov; Donna.Walsh@fda.hhs.gov; Zhiwei.Zhang@fda.hhs.gov NR 18 TC 0 Z9 0 U1 2 U2 6 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0090-3973 EI 1945-7553 J9 J TEST EVAL JI J. Test. Eval. PD MAY PY 2014 VL 42 IS 3 BP 550 EP 556 DI 10.1520/JTE20130069 PG 7 WC Materials Science, Characterization & Testing SC Materials Science GA AU5JU UT WOS:000345643800018 ER PT J AU Girman, CJ Faries, D Ryan, P Rotelli, M Belger, M Binkowitz, B O'Neill, R AF Girman, Cynthia J. Faries, Douglas Ryan, Patrick Rotelli, Matt Belger, Mark Binkowitz, Bruce O'Neill, Robert CA Drug Informat Assoc TI Pre-study feasibility and identifying sensitivity analyses for protocol pre-specification in comparative effectiveness research SO JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH LA English DT Article DE comparative effectiveness; empirical equipoise; feasibility; observational study; pharmacoepidemiology; sensitivity analysis ID TASK-FORCE REPORT; MEDICAL OUTCOMES PARTNERSHIP; SECONDARY DATA SOURCES; HEALTH-CARE DATA; EMPIRICAL-ASSESSMENT; OBSERVATIONAL DATA; RANDOMIZED-TRIALS; PROPENSITY SCORES; CAUSAL INFERENCE; CLINICAL-TRIALS AB The use of healthcare databases for comparative effectiveness research (CER) is increasing exponentially despite its challenges. Researchers must understand their data source and whether outcomes, exposures and confounding factors are captured sufficiently to address the research question. They must also assess whether bias and confounding can be adequately minimized. Many study design characteristics may impact on the results; however, minimal if any sensitivity analyses are typically conducted, and those performed are post hoc. We propose pre-study steps for CER feasibility assessment and to identify sensitivity analyses that might be most important to pre-specify to help ensure that CER produces valid interpretable results. C1 [Girman, Cynthia J.] Merck Sharp & Dohme Ltd, Ctr Observat & Real World Evidence, Comparat & Outcomes Evidence, N Wales, PA 19454 USA. [Faries, Douglas; Belger, Mark] Eli Lilly & Co, Global Stat Sci, Indianapolis, IN 46285 USA. [Ryan, Patrick] Janssen Res & Dev, UK Epidemiol Analyt, Titusville, NJ USA. [Rotelli, Matt] Eli Lilly & Co, Global PK PD & Pharmacometr, Indianapolis, IN 46285 USA. [Binkowitz, Bruce] Merck Sharp & Dohme Ltd, Late Dev Stat, Rahway, NJ 07065 USA. [O'Neill, Robert] US FDA, Off Translat Sci, CDER, Rockville, MD 20857 USA. RP Girman, CJ (reprint author), Merck Sharp & Dohme Ltd, Ctr Observat & Real World Evidence, Comparat & Outcomes Evidence, N Wales, PA 19454 USA. EM cindy_girman@merck.com NR 50 TC 3 Z9 3 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 2042-6305 EI 2042-6313 J9 J COMP EFFECT RES JI J. Comp. Eff. Res. PD MAY PY 2014 VL 3 IS 3 BP 259 EP 270 DI 10.2217/CER.14.16 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AN0ML UT WOS:000340278600014 PM 24969153 ER PT J AU Gorski, L Cooley, MB Quinones, B Oryang, D Mandrell, RE AF Gorski, Lisa Cooley, Michael B. Quinones, Beatriz Oryang, David Mandrell, Robert E. TI Prevalence of shigatoxin producing Escherichia coli, Salmonella enterica and Listeria monocytogenes at public access watershed sites in a California Central Coast agricultural region (vol 4, pg 30, 2014) SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY LA English DT Correction DE STEC; salmonella; listeria monocytogenes; watersheds; agriculture C1 [Gorski, Lisa; Cooley, Michael B.; Quinones, Beatriz; Mandrell, Robert E.] ARS, USDA, Albany, CA 94710 USA. [Oryang, David] US FDA, Div Risk Anal, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Gorski, L (reprint author), ARS, USDA, Albany, CA 94710 USA. EM lisa.gorski@ars.usda.gov NR 1 TC 1 Z9 1 U1 0 U2 5 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 2235-2988 J9 FRONT CELL INFECT MI JI Front. Cell. Infect. Microbiol. PD MAY PY 2014 VL 4 AR 58 DI 10.3389/fcimb.2014.00058 PG 1 WC Immunology; Microbiology SC Immunology; Microbiology GA AL2WR UT WOS:000338986800005 ER PT J AU Ladner, JT Beitzel, B Chain, PSG Davenport, MG Donaldson, EF Frieman, M Kugelman, JR Kuhn, JH O'Rear, J Sabeti, PC Wentworth, DE Wiley, MR Yu, GY Sozhamannan, S Bradburne, C Palacios, G AF Ladner, Jason T. Beitzel, Brett Chain, Patrick S. G. Davenport, Matthew G. Donaldson, Eric F. Frieman, Matthew Kugelman, Jeffrey R. Kuhn, Jens H. O'Rear, Jules Sabeti, Pardis C. Wentworth, David E. Wiley, Michael R. Yu, Guo-Yun Sozhamannan, Shanmuga Bradburne, Christopher Palacios, Gustavo CA Threat Characterization Consortium TI Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing SO MBIO LA English DT Editorial Material ID DISCOVERY; VIRUSES; CORONAVIRUS; POPULATION; DIVERSITY; CHINA AB Thanks to high-throughput sequencing technologies, genome sequencing has become a common component in nearly all aspects of viral research; thus, we are experiencing an explosion in both the number of available genome sequences and the number of institutions producing such data. However, there are currently no common standards used to convey the quality, and therefore utility, of these various genome sequences. Here, we propose five "standard" categories that encompass all stages of viral genome finishing, and we define them using simple criteria that are agnostic to the technology used for sequencing. We also provide genome finishing recommendations for various downstream applications, keeping in mind the cost-benefit trade-offs associated with different levels of finishing. Our goal is to define a common vocabulary that will allow comparison of genome quality across different research groups, sequencing platforms, and assembly techniques. C1 [Ladner, Jason T.; Beitzel, Brett; Kugelman, Jeffrey R.; Wiley, Michael R.; Yu, Guo-Yun; Palacios, Gustavo] US Army, Med Res Inst Infect Dis, Ctr Genome Sci, Ft Detrick, MD 21702 USA. [Chain, Patrick S. G.] Los Alamos Natl Lab, Bioinformat & Analyt Team, Biosci Div, Los Alamos, NM USA. [Davenport, Matthew G.; Bradburne, Christopher] Johns Hopkins Univ, Appl Phys Lab, Natl Secur Syst Biol Ctr, Asymmetr Operat Sect, Laurel, MD USA. [Donaldson, Eric F.; O'Rear, Jules] US FDA, Silver Spring, MD USA. [Frieman, Matthew] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA. [Sabeti, Pardis C.] Harvard Univ, Dept Organism & Evolutionary Biol, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Sabeti, Pardis C.] Broad Inst, Cambridge, MA USA. [Wentworth, David E.] J Craig Venter Inst, Rockville, MD USA. [Threat Characterization Consortium] Def Threat Reduct Agcy, Threat Characterizat Consortium, Ft Belvoir, VA USA. [Sozhamannan, Shanmuga] GoldBelt Raven LLC, Frederick, MD USA. [Sozhamannan, Shanmuga] Joint Program Execut Off, Crit Reagents Program, Ft Detrick, MD USA. RP Ladner, JT (reprint author), US Army, Med Res Inst Infect Dis, Ctr Genome Sci, Ft Detrick, MD 21702 USA. EM jason.t.ladner.ctr@mail.mil; gustavo.f.palacios.ctr@mail.mil RI Kuhn, Jens H./B-7615-2011; Palacios, Gustavo/I-7773-2015; OI Kuhn, Jens H./0000-0002-7800-6045; Palacios, Gustavo/0000-0001-5062-1938; Wentworth, David/0000-0002-5190-980X; Chain, Patrick/0000-0003-3949-3634 FU NIAID NIH HHS [HHSN272200700016I]; PHS HHS [HHSN272200700016I] NR 23 TC 20 Z9 20 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAY-JUN PY 2014 VL 5 IS 3 AR e01360-14 DI 10.1128/mBio.01360-14 PG 5 WC Microbiology SC Microbiology GA AL1HH UT WOS:000338875900037 PM 24939889 ER PT J AU O'Donoghue, AC Sullivan, HW Aikin, KJ Betts, KR AF O'Donoghue, Amie C. Sullivan, Helen W. Aikin, Kathryn J. Betts, Kevin R. TI Important Safety Information or Important Risk Information? A Question of Framing in Prescription Drug Advertisements SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE prescription drugs; drug risk; advertising; message framing; risk perception ID BEHAVIOR AB The summary of risks in a prescription drug print advertisement is typically headlined either "Important Safety Information" or "Important Risk Information." Research has shown that words used to frame information can influence interpretation of the information. We examined the impact of headline framing on risk perception among consumers viewing prescription drug ads. Participants (N = 2000) were randomly assigned to see the title "Important Safety Information" or "Important Risk Information" before reading a description of risks for a fictitious drug. Participants then answered questions about the perceived risk of the drug, attempted to recall the section heading, and reported demographic characteristics. Results revealed no differences between participants in the 2 conditions, suggesting that framing drug risk information in terms of its safety or risk does not differentially affect consumer risk perception. C1 [O'Donoghue, Amie C.; Sullivan, Helen W.; Aikin, Kathryn J.; Betts, Kevin R.] US FDA, Silver Spring, MD 20993 USA. RP O'Donoghue, AC (reprint author), US FDA, Off Prescript Drug Promot, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Amie.Odonoghue@fda.hhs.gov FU US Food and Drug Administration (FDA) FX This study had no external funding source; it was funded entirely by the US Food and Drug Administration (FDA). The authors are all employed by the FDA. NR 4 TC 0 Z9 0 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 EI 2168-4804 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD MAY PY 2014 VL 48 IS 3 BP 305 EP 307 DI 10.1177/2168479013510306 PG 3 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA AL2WA UT WOS:000338985100003 ER PT J AU Anderson, DM McGillicuddy, DJ DeGrasse, SL Sellner, KG Bricelj, VM Turner, JT Townsend, DW Kleindinst, JL AF Anderson, Donald M. McGillicuddy, Dennis J., Jr. DeGrasse, Stacey L. Sellner, Kevin G. Bricelj, V. Monica Turner, Jefferson T. Townsend, David W. Kleindinst, Judith L. TI Special Issue: Harmful Algae in the Gulf of Maine: Oceanography, Population Dynamics, and Toxin Transfer in the Food Web Preface SO DEEP-SEA RESEARCH PART II-TOPICAL STUDIES IN OCEANOGRAPHY LA English DT Editorial Material C1 [Anderson, Donald M.; McGillicuddy, Dennis J., Jr.; Kleindinst, Judith L.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. [DeGrasse, Stacey L.] US FDA, College Pk, MD USA. [Sellner, Kevin G.] Chesapeake Res Consortium, Edgewater, MD 21037 USA. [Bricelj, V. Monica] Rutgers State Univ, New Brunswick, NJ 08901 USA. [Turner, Jefferson T.] Univ Massachusetts Dartmouth, N Dartmouth, MA 02747 USA. [Townsend, David W.] Univ Maine, Orono, ME 04469 USA. RP Anderson, DM (reprint author), Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. EM danderson@whoi.edu NR 4 TC 1 Z9 1 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0645 EI 1879-0100 J9 DEEP-SEA RES PT II JI Deep-Sea Res. Part II-Top. Stud. Oceanogr. PD MAY PY 2014 VL 103 BP 1 EP 5 DI 10.1016/j.dsr2.2014.02.007 PG 5 WC Oceanography SC Oceanography GA AL0IM UT WOS:000338810600001 ER PT J AU DeGrasse, S Conrad, S DiStefano, P Vanegas, C Wallace, D Jensen, P Hickey, JM Cenci, F Pitt, J Deardorff, D Rubio, F Easy, D Donovan, MA Laycock, M Rouse, D Mullen, J AF DeGrasse, Stacey Conrad, Stephen DiStefano, Paul Vanegas, Camilo Wallace, David Jensen, Pete Hickey, J. Michael Cenci, Florence Pitt, Jaclyn Deardorff, Dave Rubio, Fernando Easy, Dorothy Donovan, Mary Anne Laycock, Maurice Rouse, Debbie Mullen, John TI Onboard screening dockside testing as a new means of managing paralytic shellfish poisoning risks in federally closed waters SO DEEP-SEA RESEARCH PART II-TOPICAL STUDIES IN OCEANOGRAPHY LA English DT Article DE Field kits; Georges Bank; Management; Offshore waters; Paralytic shellfish poisoning; Quahogs; Saxitoxin; Surfclams ID GEORGES BANK; ALEXANDRIUM-FUNDYENSE; MAINE; BLOOMS; TOXINS; GULF AB Paralytic shellfish poisoning (PSP) is the foodborne intoxication associated with the consumption of seafood contaminated with naturally occurring neurotoxins known as paralytic shellfish toxins. To protect public health from this potentially fatal syndrome, harvesting closures are implemented when toxins exceed the regulatory action level. Traditional monitoring programs established by state shellfish authorities allow for timely closures in state waters with minimal negative impacts on industry. However, such monitoring programs are not feasible in federal offshore waters given their distance from shore and the range of their spatial coverage. Thus innovative management strategies were investigated for these offshore resources. Georges Bank, an offshore resource with an estimated market value of more than $3 billion in Atlantic surfclams and ocean quahogs, has been closed to harvesting following a temporary ban in 1989 and a subsequent indefinite closure in 1990 due to the risk of PSP. As a means of managing this risk and allowing harvest of safe shellfish from this important resource, the Onboard Screening Dockside Testing Protocol (referred to as the Protocol) was developed by the US Food and Drug Administration (FDA), National Marine Fisheries Service (NMFS), state shellfish control authorities, and industry. The Protocol, which sets forth control measures to ensure product safety and public health protection, was endorsed by the Interstate Shellfish Sanitation Conference (ISSC) for pilot testing. Briefly, the pilot study Protocol required that (1) the fishing vessel receive a permit from NMFS to harvest in closed waters, (2) a minimum of five shellfish samples per intended harvest lot be tested for PSP toxins onboard, and (3) harvesting only occur when the samples tested from the intended fishing area are negative using the Jellett Rapid Tests or Abraxis Shipboard ELISA kits. Finally, product landed under the Protocol was confirmed to be safe for consumption using the mouse bioassay (MBA) prior to its introduction into commerce. This paper presents data from the pilot study, with primary focus on the advantages and challenges of the field kits employed onboard compared to the dockside MBA, which has served as the longstanding regulatory method for PSP toxins. In 2010 alone, the successful pilot study resulted in the safe harvest of over $2.7 million worth of surfclams in an area that has otherwise been unavailable for decades. Due to the success of this pilot study, the Protocol was adopted into the National Shellfish Sanitation Program Model Ordinance as an approved marine biotoxin control strategy for use in federal waters at the 2011 ISSC Biennial Meeting. In January 2013 a portion of Georges Bank was reopened for the harvest of Atlantic surfclams and ocean quahogs to fishermen following the Protocol. Published by Elsevier Ltd. C1 [DeGrasse, Stacey; Conrad, Stephen; DiStefano, Paul; Vanegas, Camilo] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Wallace, David; Jensen, Pete] Wallace & Associates, Cambridge, MD 21613 USA. [Hickey, J. Michael] Massachusetts Div Marine Fisheries, New Bedford, MA 02740 USA. [Cenci, Florence] Massachusetts Div Marine Fisheries, Gloucester, MA 01930 USA. [Pitt, Jaclyn; Deardorff, Dave; Rubio, Fernando] Abraxis LLC, Warminster, PA 18974 USA. [Easy, Dorothy; Donovan, Mary Anne; Laycock, Maurice] Jellett Rapid Testing Ltd, Chester Basin, NS B0J 1K0, Canada. [Rouse, Debbie] Delaware Dept Nat Resources, Dover, DE 19904 USA. [Mullen, John] Rhode Isl Dept Hlth, Div Food Protect, Providence, RI 02908 USA. RP DeGrasse, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Stacey.DeGrasse@fda.hhs.gov OI DeGrasse, Stacey/0000-0001-7808-4193 FU NOAA/ECOHAB program FX This pilot study would not have been possible without the willingness and dedication of the crew of F/V Sea Watcher I and their sister ship F/V Misty Dawn. The crew of the Misty Dawn participated in the early phase and background portion of this study, and the crew of the Sea Watcher I actually collected samples and performed the onboard screening for all the samples presented in this manuscript. We particularly thank M. Rencurrel for leading the onboard screening efforts. Thanks to H. Morgan of Jellett Rapid Testing. We also extend special thanks to M. Abbott, J. Callahan, and B. Marshall for their significant contributions to the pilot study and J. DeGrasse for review of the manuscript. We thank our GOMTOX collaborators, in particular D. Anderson, for providing important ancillary data and context. S.L.D. received partial funding for her work on this study through the NOAA/ECOHAB program; this manuscript is NOAA contribution #676. We extend a special thanks to Q. Dortch for her guidance and oversight with the management of the ECOHAB program. We acknowledge our colleagues at NOAA/NMFS, especially K. Chu, who have worked with us to provide the necessary permits and approvals for conducting the pilot study. We thank C. Alexander of NJ Department of Health and Senior Services for support and participation in the pilot study. Lastly, we would like to extend gratitude to K. Moore and the ISSC Executive Board for working closely with all of us on the Protocol, for granting the necessary approvals to conduct the pilot study, and for the recent adoption of the Protocol as a means to control marine biotoxins in federal offshore waters. NR 23 TC 5 Z9 6 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0645 EI 1879-0100 J9 DEEP-SEA RES PT II JI Deep-Sea Res. Part II-Top. Stud. Oceanogr. PD MAY PY 2014 VL 103 BP 288 EP 300 DI 10.1016/j.dsr2.2013.01.036 PG 13 WC Oceanography SC Oceanography GA AL0IM UT WOS:000338810600021 ER PT J AU DeGrasse, S Vanegas, C Conrad, S AF DeGrasse, Stacey Vanegas, Camilo Conrad, Stephen TI Paralytic shellfish toxins in the sea scallop Placopecten magellanicus on Georges Bank: Implications for an offshore roe-on and whole scallop fishery SO DEEP-SEA RESEARCH PART II-TOPICAL STUDIES IN OCEANOGRAPHY LA English DT Article DE Georges Bank; Gonad; Paralytic shellfish toxins; Placopecten magellanicus; Saxitoxin; Viscera ID SINGLE-LABORATORY VALIDATION; RECEPTOR-BINDING ASSAY; ALEXANDRIUM-FUNDYENSE; BLOOMS; POISON; MAINE; GULF AB To protect public health from the potential risk of paralytic shellfish poisoning (PSP) in sea scallops, Placopecten magellanicus, from the Atlantic offshore U.S. waters of Georges Bank, harvesting of roe-on or whole scallops is banned. Only adductor muscles may be sold if harvested from Georges Bank, Gulf of Maine, or the PSP closure areas as far west as 71 West Longitude. Given the limited toxicity data available for sea scallops from this region both prior to and subsequent to implementation of this management strategy, this study sought a more extensive spatial and temporal evaluation of sea scallop gonad and viscera toxicities that would inform management decisions related to the roe-on and whole scallop fishery. Both overall toxicity and toxin composition were measured for sea scallop gonads and viscera collected from 232 stations in 2007 and 23 in 2010. Overall toxicity was assessed using two screening methods: field-deployable Jellett Rapid Tests URT) and quantitative, laboratory-based receptor binding assays (in 2007). Additionally, a quantitative liquid chromatography with fluorescence detection (LC-FD) method was used to determine toxin composition and overall toxicity (in 2010). The at-sea qualitative JRT screening tool results, whereby a positive indicated the sample contained at least 40 mu g saxitoxin (STX) equivalents 100 g(-1), were often inconsistent with results obtained using the quantitative methods. Sea scallop viscera toxicity represented the majority of toxin load in the organism and was often in excess of the regulatory guidance level. Sea scallop gonads accounted for a small percentage of total toxicity, but at times reached unsafe levels. Toxin composition in both the gonads and viscera was dominated by STX and gonyautoxin 2/3, as has been reported in previous studies. No predictive indices of gonad toxicity were found. Results at this time do not support a roe-on or whole scallop fishery on Georges Bank. While access restrictions to whole scallops on Georges Bank are unlikely to change based on these results, it seems plausible that a management strategy requiring at-sea testing of scallop gonads for PSP may be necessary in order for a safe roe-on scallop fishery from this region to be feasible. Published by Elsevier Ltd. C1 [DeGrasse, Stacey; Vanegas, Camilo; Conrad, Stephen] US FDA, Ctr Food Safety & Appl Nutr, Div Analyt Chem, Spect & Mass Spectrometry Branch, College Pk, MD 20740 USA. RP DeGrasse, S (reprint author), CFSAN, FDA, Div Analyt Chem, Off Regulatory Sci, 5100 Paint Branch Pkwy,HFS-707, College Pk, MD 20740 USA. EM Stacey.Degrasse@fda.hhs.gov OI DeGrasse, Stacey/0000-0001-7808-4193 FU NOAA Fisheries Service; Northeast Fisheries Science Center; ECOHAB program of the National Oceanic and Atmospheric Administration [732] FX We gratefully acknowledge the NOAA Fisheries Service and Northeast Fisheries Science Center for their support and allowing our special sample collections on the sea scallop surveys. We especially appreciate the sampling assistance by Russell Brown, Vic Nordahl, Sean Lucey, Stacy Rowe, and Dvora Hart. Thanks to the captain and crew of the R/V Albatross IV and R/V Hugh R. Sharp. We also thank Greg Noonan, Vickery Brewer, Melissa Ellwanger, Raymond Burditt, Niko Has, Kevin Crandell, Sarah Yachetti, Ben Broder-Oldach, and Kevin Reuter for assistance with sample collection/preparation. We acknowledge Melissa Abbott and Paul Distefano for their insight on sea scallop policy guidance in the U.S. and Jeffrey van de Riet for the same in Canada. We thank Geoffrey Day and Richard Taylor for helpful comments that improved the quality of the manuscript. We acknowledge Jeff DeGrasse and John Callahan for thorough reviews of the manuscript. We extend gratitude to the ECOHAB GOMTOX investigators for providing ancillary data and context, which allowed a greater interpretation of this research. This work was partially funded by the ECOHAB program of the National Oceanic and Atmospheric Administration and represents contribution #732. NR 25 TC 2 Z9 2 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0645 EI 1879-0100 J9 DEEP-SEA RES PT II JI Deep-Sea Res. Part II-Top. Stud. Oceanogr. PD MAY PY 2014 VL 103 BP 301 EP 307 DI 10.1016/j.dsr2.2013.05.013 PG 7 WC Oceanography SC Oceanography GA AL0IM UT WOS:000338810600022 ER PT J AU Deeds, JR Petitpas, CM Shue, V White, KD Keafer, BA McGillicuddy, DJ Milligan, PJ Anderson, DM Turner, JT AF Deeds, Jonathan R. Petitpas, Christian M. Shue, Vangie White, Kevin D. Keafer, Bruce A. McGillicuddy, Dennis J., Jr. Milligan, Peter J. Anderson, Donald M. Turner, Jefferson T. TI PSP toxin levels and plankton community composition and abundance in size-fractionated vertical profiles during spring/summer blooms of the toxic dinoflagellate Alexandrium fundyense in the Gulf of Maine and on Georges Bank, 2007, 2008, and 2010: 1. Toxin levels SO DEEP-SEA RESEARCH PART II-TOPICAL STUDIES IN OCEANOGRAPHY LA English DT Article DE Harmful algal bloom; PSP toxins; Alexandrium sp.; Vectorial intoxication; Gulf of Maine; Georges Bank ID PARALYTIC SHELLFISH TOXINS; NORTHEASTERN UNITED-STATES; APRIL-JUNE 1998; PLACOPECTEN-MAGELLANICUS; TROPHIC ACCUMULATION; SEA SCALLOP; CASCO BAY; ZOOPLANKTON; WHALES; CANADA AB As part of the NOAA ECOHAB funded Gulf of Maine Toxicity (GOMTOX)(1) project, we determined Alexandrium fundyense abundance, paralytic shellfish poisoning (PSP) toxin composition, and concentration in quantitatively-sampled size-fractionated (20-64, 64-100, 100-200, 200-500, and >500 mu m) particulate water samples, and the community composition of potential grazers of A. fundyense in these size fractions, at multiple depths (typically 1, 10, 20 m, and near-bottom) during 10 large-scale sampling cruises during the A. fundyense bloom season (May-August) in the coastal Gulf of Maine and on Georges Bank in 2007, 2008, and 2010. Our findings were as follows: (1) when all sampling stations and all depths were summed by year, the majority (94% +/- 4%) of total PSP toxicity was contained in the 20-64 mu m size fraction; (2) when further analyzed by depth, the 20-64 mu m size fraction was the primary source of toxin for 97% of the stations and depths samples over three years; (3) overall PSP toxin profiles were fairly consistent during the three seasons of sampling with gonyautoxins (I, 2, 3, and 4) dominating (90.7% +/- 5.5%), followed by the carbamate toxins saxitoxin (STX) and neosaxitoxin (NEO) (7.7% +/- 4.5%), followed by n-sulfocarbamoyl toxins (Cl and 2, GTX5) (13% +/- 0.6%), followed by all decarbamoyl toxins (dcSTX, dcNEO, dcGTX2823) (< 1%), although differences were noted between PSP toxin compositions for nearshore coastal Gulf of Maine sampling stations compared to offshore Georges Bank sampling stations for 2 out of 3 years; (4) surface cell counts of A. fundyense were a fairly reliable predictor of the presence of toxins throughout the water column; and (5) nearshore surface cell counts of A. fundyense in the coastal Gulf of Maine were not a reliable predictor of A. fundyense populations offshore on Georges Bank for 2 out of the 3 years sampled. Published by Elsevier Ltd. C1 [Deeds, Jonathan R.; Shue, Vangie; White, Kevin D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Petitpas, Christian M.; Milligan, Peter J.; Turner, Jefferson T.] Univ Massachusetts Dartmouth, Sch Marine Sci & Technol, New Bedford, MA 02744 USA. [Keafer, Bruce A.; Anderson, Donald M.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. [McGillicuddy, Dennis J., Jr.] Woods Hole Oceanog Inst, Dept Appl Ocean Phys & Engn, Woods Hole, MA 02543 USA. RP Deeds, JR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jonathan.deeds@fda.hhs.gov FU Massachusetts Water Resources Authority; FDA; Thomas Jefferson High School for Science and Technology Mentorship Program; National Oceanic and Atmospheric Administration [NA06NOS4780245]; Woods Hole Center for Oceans and Human Health through National Science Foundation [OCE-0430724, OCE-0911031]; National Institute of Environmental Health Sciences [1P50-ES01274201] FX We are very grateful for the outstanding efforts of the officers, crews, and shore support of R/V Oceanus, R/V Endeavor, and R/V Tioga, as well as the hard work of all those who participated in the seagoing science teams. Special thanks to Edward Durbin and Peter Wiebe for the loan of the plankton pumping systems used in this study. Additional thanks go to Scott Libby of Battelle for use of A. fundyense abundance data from monitoring funded by the Massachusetts Water Resources Authority. Vangie Shue, who contributed significantly to the toxin analysis portion of this project, was supported through the FDA and also through the Thomas Jefferson High School for Science and Technology Mentorship Program. Research support was provided by National Oceanic and Atmospheric Administration Grant NA06NOS4780245 for the Gulf of Maine Toxicity (GOMTOX) program. BAK, DJM, and DMA were partially supported by the Woods Hole Center for Oceans and Human Health through National Science Foundation Grants OCE-0430724 and OCE-0911031 and National Institute of Environmental Health Sciences Grant 1P50-ES01274201. This manuscript is NOAA ECOHAB contribution # 736. NR 39 TC 7 Z9 7 U1 2 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0645 EI 1879-0100 J9 DEEP-SEA RES PT II JI Deep-Sea Res. Part II-Top. Stud. Oceanogr. PD MAY PY 2014 VL 103 BP 329 EP 349 DI 10.1016/j.dsr2.2013.04.013 PG 21 WC Oceanography SC Oceanography GA AL0IM UT WOS:000338810600025 PM 25076816 ER PT J AU Petitpas, CM Turner, JT Deeds, JR Keafer, BA McGillicuddy, DJ Milligan, PJ Shue, V White, KD Anderson, DM AF Petitpas, Christian M. Turner, Jefferson T. Deeds, Jonathan R. Keafer, Bruce A. McGillicuddy, Dennis J., Jr. Milligan, Peter J. Shue, Vangie White, Kevin D. Anderson, Donald M. TI PSP toxin levels and plankton community composition and abundance in size-fractionated vertical profiles during spring/summer blooms of the toxic dinofiagellate Alexandrium fundyense in the Gulf of Maine and on Georges Bank, 2007, 2008, and 2010: 2. Plankton community composition and abundance SO DEEP-SEA RESEARCH PART II-TOPICAL STUDIES IN OCEANOGRAPHY LA English DT Article DE Harmful algal bloom; PSP toxins; ZooplanIcton; Vectorial intoxication; Gulf of Maine; Georges Bank ID RED TIDE DINOFLAGELLATE; APRIL-JUNE 1998; CASCO BAY; TROPHIC ACCUMULATION; ZOOPLANKTON; HYDROIDS; PHYTOPLANKTON; DINOPHYCEAE; TAMARENSE; GRAZERS AB As part of the Gulf of Maine Toxicity (GOMTOX(1)) project, we determined Alexandrium fundyense abundance, paralytic shellfish poisoning (PSP) toxin levels in various plankton size fractions, and the community composition of potential grazers of A. fundyense in plankton size fractions during blooms of this toxic dinoflagellate in the coastal Gulf of Maine and on Georges Bank in spring and summer of 2007, 2008, and 2010. PSP toxins and A. fundyense cells were found throughout the sampled water column (down to 50 m) in the 20-64 gm size fractions. While PSP toxins were widespread throughout all size classes of the zooplankton grazing community, the majority of the toxin was measured in the 20-64 mu m size fraction. A. fundyense cellular toxin content estimated from field samples was significantly higher in the coastal Gulf of Maine than on Georges Bank. Most samples containing PSP toxins in the present study had diverse assemblages of grazers. However, some samples clearly suggested PSP toxin accumulation in several different grazer taxa including tintinnids, heterotrophic dinoflagellates of the genus Protoper-idinium, barnacle nauplii, the harpacticoid copepod Microsetella norvegica, the calanoid copepods Calanus finmarchicus and Pseudocalanus spp., the marine cladoceran Evadne nordmanni, and hydroids of the genus Clytia. Thus, a diverse assemblage of zooplankton grazers accumulated PSP toxins through food-web interactions. This raises the question of whether PSP toxins pose a potential human health risk not only from nearshore bivalve shellfish, but also potentially from fish and other upper-level consumers in zooplankton-based pelagic food webs. (c) 2013 Elsevier Ltd. All rights reserved. C1 [Petitpas, Christian M.; Turner, Jefferson T.; Milligan, Peter J.] Univ Massachusetts Dartmouth, Sch Marine Sci & Technol, New Bedford, MA 02744 USA. [Deeds, Jonathan R.; Shue, Vangie; White, Kevin D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Keafer, Bruce A.; Anderson, Donald M.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. [McGillicuddy, Dennis J., Jr.] Woods Hole Oceanog Inst, Dept Appl Ocean Phys & Engn, Woods Hole, MA 02543 USA. RP Petitpas, CM (reprint author), Univ Massachusetts Dartmouth, Sch Marine Sci & Technol, 706 South Rodney French Blvd, New Bedford, MA 02744 USA. EM cjadlowic@umassd.edu FU National Oceanic and Atmospheric Administration [NA06N054780245]; Woods Hole Center for Oceans and Human Health through National Science Foundation [OCE-0430724, OCE-0911031]; National Institute of Environmental Health Sciences [1P50-ES01274201] FX We are very grateful for the outstanding efforts of the officers, crews, and shore support of R/V Oceanus, R/V Endeavor, and R/V Tioga, as well as the hard work of all those who participated in the seagoing science teams. Thanks also to Edward Durbin and Peter Wiebe for the loan of the plankton pumping systems. Research support was provided by National Oceanic and Atmospheric Administration grant NA06N054780245 for the Gulf of Maine Toxicity (GOMTOX) program. BAK, DJM, and DMA were partially supported by the Woods Hole Center for Oceans and Human Health through National Science Foundation grants OCE-0430724 and OCE-0911031 and National Institute of Environmental Health Sciences grant 1P50-ES01274201. NR 44 TC 6 Z9 6 U1 4 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0645 EI 1879-0100 J9 DEEP-SEA RES PT II JI Deep-Sea Res. Part II-Top. Stud. Oceanogr. PD MAY PY 2014 VL 103 BP 350 EP 367 DI 10.1016/j.dsr2.2013.04.012 PG 18 WC Oceanography SC Oceanography GA AL0IM UT WOS:000338810600026 PM 26236112 ER PT J AU DeGrasse, S Rivera, V Roach, J White, K Callahan, J Couture, D Simone, K Peredy, T Poli, M AF DeGrasse, Stacey Rivera, Victor Roach, John White, Kevin Callahan, John Couture, Darcie Simone, Karen Peredy, Tamas Poli, Mark TI Paralytic shellfish toxins in clinical matrices: Extension of AOAC official method 2005.06 to human urine and serum and application to a 2007 case study in Maine SO DEEP-SEA RESEARCH PART II-TOPICAL STUDIES IN OCEANOGRAPHY LA English DT Article DE LC; -FD Paralytic shellfish poisoning; Saxitoxin; Serum; Urine ID SINGLE-LABORATORY VALIDATION; POSTMORTEM ANALYSIS; NEOSAXITOXIN; SAXITOXIN; SAMPLES; PSP AB Paralytic shellfish poisoning (PSP), a potentially fatal foodborne illness, is often diagnosed anecdotally based on symptoms and dietary history. The neurotoxins responsible for PSP, collectively referred to as the saxitoxins or paralytic shellfish toxins (PSTs), are natural toxins, produced by certain dinoflagellates, that may accumulate in seafood, particularly filter-feeding bivalves. Illnesses are rare because of effective monitoring programs, yet occasional poisonings occur. Rarely are contaminated food and human clinical samples (e.g., urine and serum) available for testing. There are currently few methods, none of which are validated, for determining PSTs in clinical matrices. This study evaluated AOAC (Association of Analytical Communities) Official Method of Analysis (OMA) 2005.06. [AOAC Official Method 2005.06 Paralytic Shellfish Poisoning Toxins in Shellfish: Prechormatographic Oxidation and Liquid Chromatography with Fluorescence Detection. In Official Methods of Analysis of AOAC International < http://www.eoma.aoac.org >],validatedonlyfor shellfish extracts, for its extension to human urine and serum samples. Initial assessment of control urine and serum matrices resulted in a sample cleanup modification when working with urine to remove hippuric acid, a natural urinary compound of environmental/dietary origin, which co-eluted with saxitoxin. Commercially available urine and serum matrices were then quantitatively spiked with PSTs that were available as certified reference materials (STX, dcSTX, BI, GTX2/3, C1/2, NEO, and GTX1/4) to assess method performance characteristics. The method was subsequently applied successfully to a PSP case study that occurred in July 2007 in Maine. Not only were PSTs identified in the patient urine and serum samples, the measured time series also led to the first report of human PST-specific urinary elimination rates. The LC-FD data generated from this case study compared remarkably well to results obtained using AOAC OMA 2011.27 [AOAC Official Method 2011.27 Paralytic Shellfish Toxins (PSTs) in Shellfish, Receptor Binding Assay. In Official Methods of Analysis of AOAC International < http://www.eoma.aoac.org >], further demonstrating successful extension of the LC-FD method to these clinical matrices. Moreover, data generated from this poisoning event reiterated that urine is a preferable clinical matrix, compared to serum, for diagnostic purposes due to higher accumulation and longer residence times in urine. Published by Elsevier Ltd. C1 [DeGrasse, Stacey; Roach, John; White, Kevin; Callahan, John] US FDA, Ctr Food Safety & Appl Nutr, Div Analyt Chem, Spect & Mass Spectrometry Branch, College Pk, MD 20740 USA. [Rivera, Victor; Poli, Mark] US Army Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Couture, Darcie] Maine Dept Marine Resources, West Boothbay Harbor, ME 04575 USA. [Simone, Karen; Peredy, Tamas] Northern New England Poison Ctr, Portland, ME 04103 USA. RP DeGrasse, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Analyt Chem, Spect & Mass Spectrometry Branch, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Stacey.Degrasse@fda.hhs.gov OI DeGrasse, Stacey/0000-0001-7808-4193 FU JSTO-CBD/DTRA [05-4-81-051] FX This project was funded by JSTO-CBD/DTRA, Research Plan No. 05-4-81-051. We would like to acknowledge Luis Raez, Laurie Leder, Ellen Boudreau, Christa Madock, and Sarah Yachetti for technical assistance in the laboratory and Steve Conrad for data presentation assistance. We thank Lorrie Backer and Amy Robbins for information regarding illness reports and documented case studies in Maine. We extend gratitude to Douglas Osborne for assistance regarding human use approvals. We thank two anonymous reviewers for thorough comments that improved the quality of the manuscript. NR 26 TC 5 Z9 5 U1 2 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0645 EI 1879-0100 J9 DEEP-SEA RES PT II JI Deep-Sea Res. Part II-Top. Stud. Oceanogr. PD MAY PY 2014 VL 103 BP 368 EP 375 DI 10.1016/j.dsr2.2012.08.001 PG 8 WC Oceanography SC Oceanography GA AL0IM UT WOS:000338810600027 ER PT J AU Ferguson, S Law, C AF Ferguson, S. Law, C. TI Developmental methylphenidate (MPH) treatment has greater effects on certain adult female behaviors of male and female Sprague-Dawley rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Neurobehavioral-Teratology-Society CY JUN 28-JUL 02, 2014 CL Bellevue, WA SP Neurobehavioral Teratol Soc C1 [Ferguson, S.; Law, C.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2014 VL 43 MA NBTS 27 BP 84 EP 85 DI 10.1016/j.ntt.2014.04.030 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA AK7QC UT WOS:000338621800037 ER PT J AU Paule, M Liu, S Zhang, X Nerport, G Apana, S Berridge, M Silkker, W Wang, C AF Paule, M. Liu, S. Zhang, X. Nerport, G. Apana, S. Berridge, M. Silkker, W. Wang, C. TI Evaluating neural progenitor cell proliferation following sevoflurane exposure in developing rat brain using PET imaging of [F-18] fluoro-I-thymidine SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Neurobehavioral-Teratology-Society CY JUN 28-JUL 02, 2014 CL Bellevue, WA SP Neurobehavioral Teratol Soc C1 [Paule, M.; Liu, S.; Zhang, X.; Nerport, G.; Silkker, W.; Wang, C.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Apana, S.; Berridge, M.] 3 D Imaging LLC, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2014 VL 43 MA NBTS 26 BP 84 EP 84 DI 10.1016/j.ntt.2014.04.029 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA AK7QC UT WOS:000338621800036 ER PT J AU Kim, YD Lantz-McPeak, SM Ali, SF Kleinman, MT Choi, YS Kim, H AF Kim, Yong-Dae Lantz-McPeak, Susan M. Ali, Syed F. Kleinman, Michael T. Choi, Young-Sook Kim, Heon TI Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Diesel exhaust particles; Oxidative stress; Dopamine; PC-12 cells; Neurotoxicity ID AIR-POLLUTION; PARTICULATE MATTER; BRAIN; EXPOSURE; TRANSLOCATION; RECEPTORS; DISEASE; OXIDASE; SIZE AB A major constituent of urban air pollution is diesel exhaust, a complex mixture of gases, chemicals, and particles. Recent evidence suggests that exposure to air pollution can increase the risk of a fatal stroke, cause cerebrovascular damage, and induce neuroinflammation and oxidative stress that may trigger neurodegenerative diseases, such as Parkinson's disease. The specific aim of this study was to determine whether ultrafine diesel exhaust particles (DEPs), the particle component of exhaust from diesel engines, can induce oxidative stress and effect dopamine metabolism in PC-12 cells. After 24 h exposure to DEPs of 200 nm or smaller, cell viability, ROS and nitric oxide (NO2) generation, and levels of dopamine (DA) and its metabolites, (dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)), were evaluated. Results indicated cell viability was not significantly changed by DEP exposure. However, ROS showed dramatic dose-dependent changes after DEP exposure (2.4 fold increase compared to control at 200 mu g/mL). NO2 levels were also dose-dependently increased after DEP exposure. Although not in a dose-dependent manner, upon DEP exposure, intracellular DA levels were increased while DOPAC and HVA levels decreased when compared to control. Results suggest that ultrafine DEPs lead to dopamine accumulation in the cytoplasm of PC-12 cells, possibly contributing to ROS formation. Further studies are warranted to elucidate this mechanism. (C) 2014 The Authors. Published by Elsevier B.V. C1 [Kim, Yong-Dae; Choi, Young-Sook; Kim, Heon] Chungbuk Natl Univ, Coll Med, Dept Prevent Med, Cheongju 361763, Chungbuk, South Korea. [Lantz-McPeak, Susan M.; Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. [Kleinman, Michael T.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. RP Kim, YD (reprint author), Chungbuk Natl Univ, Coll Med, Dept Prevent Med, Cheongju 361763, Chungbuk, South Korea. EM ydkim@chungbuk.ac.kr; syed.ali@fda.hhs.gov OI Kim, Heon/0000-0003-0329-5249 FU Chungbuk National University FX This work was supported in part by Chungbuk National University Grant in 2011. NR 24 TC 4 Z9 4 U1 6 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 EI 1872-7077 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD MAY PY 2014 VL 37 IS 3 BP 954 EP 959 DI 10.1016/j.etap.2014.03.008 PG 6 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA AK7HB UT WOS:000338598200007 PM 24705343 ER PT J AU Walker, BN James, RH Chakravarty, A Calogero, D Ilev, IK AF Walker, Bennett N. James, Robert H. Chakravarty, Aurin Calogero, Don Ilev, Ilko K. TI Assessing the effect of laser beam width on quantitative evaluation of optical properties of intraocular lens implants SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optics; biophotonics; intraocular lens; confocal microscopy; paraxial Gaussian laser beam ID POWER MEASUREMENT; ACCURACY; CATARACT AB The design and manufacture of intraocular lenses (IOLs) depend upon the identification and quantitative preclinical evaluation of key optical properties and environmental parameters. The confocal laser method (CLM) is a new technique for measuring IOL optical properties, such as dioptric power, optical quality, refractive index, and geometrical parameters. In comparison to competing systems, the CLM utilizes a fiber-optic confocal laser design that significantly improves the resolution, accuracy, and repeatability of optical measurements. Here, we investigate the impact of changing the beam diameter on the CLM platform for the evaluation of IOL dioptric powers. Due to the Gaussian intensity profile of the CLM laser beam, the changes in focal length and dioptric power associated with changes in beam diameter are well within the tolerances specified in the ISO IOL standard. These results demonstrate some of the advanced potentials of the CLM toward more effectively and quantitatively evaluating IOL optical properties. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Walker, Bennett N.; James, Robert H.; Chakravarty, Aurin; Ilev, Ilko K.] US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Calogero, Don] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Walker, BN (reprint author), US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM bennett.walker@fda.hhs.gov OI WALKER, BENNETT/0000-0003-0221-1904 FU Oak Ridge Institute for Science and Education (ORISE) FX This work was supported by Oak Ridge Institute for Science and Education (ORISE) and is greatly appreciated. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 15 TC 2 Z9 2 U1 0 U2 4 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY PY 2014 VL 19 IS 5 AR 055004 DI 10.1117/1.JBO.19.5.055004 PG 4 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AK3OR UT WOS:000338334600016 PM 24817618 ER PT J AU He, GX Landry, M Chen, HZ Thorpe, C Walsh, D Varela, MF Pan, HM AF He, Gui-Xin Landry, Michael Chen, Huizhong Thorpe, Conner Walsh, Dennis Varela, Manuel F. Pan, Hongmiao TI Detection of benzalkonium chloride resistance in community environmental isolates of staphylococci SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; REAL-TIME PCR; PSEUDOMONAS-AERUGINOSA; ANTIBIOTIC-RESISTANCE; AUREUS; GENES; METHICILLIN; IDENTIFICATION; SMR; INFECTIONS AB We isolated a total of 653 strains from 64 community environmental samples in Massachusetts, USA. Among these isolates, 9.65% (63 strains) were benzalkonium chloride (BC)-resistant staphylococci. All BC-resistant strains were collected from surfaces upon which antibacterial wipes or antibacterial sprays containing 0.02-0.12% BC had frequently been used in the fitness centres. However, isolates from surfaces upon which antibacterial wipes or antibacterial sprays had not been used were all sensitive to BC. All BC-resistant strains were also resistant to erythromycin, penicillin and ampicillin. In addition, 51 strains showed resistance to cetyltrimethylammonium bromide (CAB), 15 strains showed resistance to chloramphenicol, 12 strains showed resistance to ciprofloxacin and four strains showed resistance to meticillin. Resistance gene analysis demonstrated that 41 strains contained qacA/B, 30 strains had qacC, 25 strains contained qacG, 16 strains had qacH and eight strains contained qacJ. These data indicate that application of BC is associated with environmental staphylococcal antimicrobial resistance. C1 [He, Gui-Xin; Landry, Michael; Thorpe, Conner; Walsh, Dennis] Univ Massachusetts Lowell, Dept Clin Lab & Nutr Sci, Lowell, MA 01854 USA. [Chen, Huizhong; Pan, Hongmiao] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Varela, Manuel F.] Eastern New Mexico Univ, Dept Biol, Portales, NM 88130 USA. RP He, GX (reprint author), Univ Massachusetts Lowell, Dept Clin Lab & Nutr Sci, Lowell, MA 01854 USA. EM Guixin_He@uml.edu FU University of Massachusetts Lowell; National Center for Research Resources [5P20RR016480-12] FX This work was supported by an Internal Research Grant from the University of Massachusetts Lowell (G. X. H.) and by grants (M. F. V.) from the National Center for Research Resources (5P20RR016480-12). We are grateful to Dr David Hooper (Massachusetts General Hospital, Boston, MA, USA) and Dr Michael Shiaris (University of Massachusetts Boston, Boston, MA, USA) for helpful comments. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 31 TC 5 Z9 5 U1 0 U2 7 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 EI 1473-5644 J9 J MED MICROBIOL JI J. Med. Microbiol. PD MAY PY 2014 VL 63 BP 735 EP 741 DI 10.1099/jmm.0.073072-0 PN 5 PG 7 WC Microbiology SC Microbiology GA AK5PQ UT WOS:000338478700014 PM 24586033 ER PT J AU Zheng, J Pettengill, J Strain, E Allard, MW Ahmed, R Zhao, SH Brown, EW AF Zheng, Jie Pettengill, James Strain, Errol Allard, Marc W. Ahmed, Rafiq Zhao, Shaohua Brown, Eric W. TI Genetic Diversity and Evolution of Salmonella enterica Serovar Enteritidis Strains with Different Phage Types SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ACTIVE SURVEILLANCE NETWORK; POPULATION-STRUCTURE; UNITED-STATES; SEROTYPE ENTERITIDIS; MAXIMUM-LIKELIHOOD; DNA-SEQUENCES; TYPING SCHEME; EPIDEMIOLOGY; PHYLOGEOGRAPHY; INCONGRUENCE AB Phage typing has been used for the epidemiological surveillance of Salmonella enterica serovar Enteritidis for over 2 decades. However, knowledge of the genetic and evolutionary relationships between phage types is very limited, making differences difficult to interpret. Here, single nucleotide polymorphisms (SNPs) identified from whole-genome comparisons were used to determine the relationships between some S. Enteritidis phage types (PTs) commonly associated with food-borne outbreaks in the United States. Emphasis was placed on the predominant phage types PT8, PT13a, and PT13 in North America. With >89,400 bp surveyed across 98 S. Enteritidis isolates representing 14 distinct phage types, 55 informative SNPs were discovered within 23 chromosomally anchored loci. To maximize the discriminatory and evolutionary partitioning of these highly homogeneous strains, sequences comprising informative SNPs were concatenated into a single combined data matrix and subjected to phylogenetic analysis. The resultant phylogeny allocated most S. Enteritidis isolates into two distinct clades (clades I and II) and four subclades. Synapomorphic (shared and derived) sets of SNPs capable of distinguishing individual clades/subclades were identified. However, individual phage types appeared to be evolutionarily disjunct when mapped to this phylogeny, suggesting that phage typing may not be valid for making phylogenetic inferences. Furthermore, the set of SNPs identified here represents useful genetic markers for strain differentiation of more clonal S. Enteritidis strains and provides core genotypic markers for future development of a SNP typing scheme with S. Enteritidis. C1 [Zheng, Jie; Pettengill, James; Strain, Errol; Allard, Marc W.; Brown, Eric W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhao, Shaohua] US FDA, Ctr Vet Med, Laurel, MD USA. [Ahmed, Rafiq] Canadian Sci Ctr Human & Anim Hlth, Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada. RP Zheng, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM jie.zheng@fda.hhs.gov NR 67 TC 5 Z9 5 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2014 VL 52 IS 5 BP 1490 EP 1500 DI 10.1128/JCM.00051-14 PG 11 WC Microbiology SC Microbiology GA AJ7XV UT WOS:000337915700028 PM 24574287 ER PT J AU Mocca, CP Brady, RA Burns, DL AF Mocca, Christopher P. Brady, Rebecca A. Burns, Drusilla L. TI Role of Antibodies in Protection Elicited by Active Vaccination with Genetically Inactivated Alpha Hemolysin in a Mouse Model of Staphylococcus aureus Skin and Soft Tissue Infections SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID PASSIVE-IMMUNIZATION; UNITED-STATES; MURINE MODEL; TOXIN; NEUTROPHILS; VANCOMYCIN; VIRULENCE; SEVERITY; GENE AB Due to the emergence of highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, S. aureus has become a major threat to public health. A majority of CA-MRSA skin and soft tissue infections in the United States are caused by S. aureus USA300 strains that are known to produce high levels of alpha hemolysin (Hla). Therefore, vaccines that contain inactivated forms of this toxin are currently being developed. In this study, we sought to determine the immune mechanisms of protection for this antigen using a vaccine composed of a genetically inactivated form of Hla (HlaH35L). Using a murine model of skin and soft tissue infections (SSTI), we found that BALB/c mice were protected by vaccination with HlaH35L; however, Jh mice, which are deficient in mature B lymphocytes and lack IgM and IgG in their serum, were not protected. Passive immunization with anti-HlaH35L antibodies conferred protection against bacterial colonization. Moreover, we found a positive correlation between the total antibody concentration induced by active vaccination and reduced bacterial levels. Animals that developed detectable neutralizing antibody titers after active vaccination were significantly protected from infection. These data demonstrate that antibodies to Hla represent the major mechanism of protection afforded by active vaccination with inactivated Hla in this murine model of SSTI, and in this disease model, antibody levels correlate with protection. These results provide important information for the future development and evaluation of S. aureus vaccines. C1 [Mocca, Christopher P.; Brady, Rebecca A.; Burns, Drusilla L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. EM drusilla.burns@fda.hhs.gov FU Center for Biologics Evaluation and Research, Food and Drug Administration FX This work was supported by the Intramural Research Program of the Center for Biologics Evaluation and Research, Food and Drug Administration. NR 29 TC 9 Z9 11 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2014 VL 21 IS 5 BP 622 EP 627 DI 10.1128/CVI.00051-14 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AJ0NU UT WOS:000337352300003 PM 24574539 ER PT J AU Bash, MC Lynn, F Mocca, B Borrow, R Findlow, H Hassan-King, M Preziosi, MP Idoko, O Sow, S Kulkarni, P LaForcec, FM AF Bash, Margaret C. Lynn, Freyja Mocca, Brian Borrow, Ray Findlow, Helen Hassan-King, Musa Preziosi, Marie-Pierre Idoko, Olubukola Sow, Samba Kulkarni, Prasad LaForcec, F. Marc TI Development and Use of a Serum Bactericidal Assay Using Pooled Human Complement To Assess Responses to a Meningococcal Group A Conjugate Vaccine in African Toddlers SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MENINGITIDIS GROUP-A; NEISSERIA-MENINGITIDIS; CAPSULAR POLYSACCHARIDE; HUMAN IMMUNITY; SEROGROUP-A; W-135; IMMUNOGENICITY; PERSISTENCE; ANTIBODY; SAFETY AB A meningococcal group A polysaccharide (PS) conjugate vaccine (PsA-TT) has been developed for African countries affected by epidemic meningitis caused by Neisseria meningitidis. Complement-mediated serum bactericidal antibody (SBA) assays are used to assess protective immune responses to meningococcal vaccination. Human complement (hC') was used in early studies demonstrating antibody-mediated protection against disease, but it is difficult to obtain and standardize. We developed and evaluated a method for sourcing hC' and then used the SBA assay with hC' (hSBA) to measure bactericidal responses to PsA-TT vaccination in 12- to 23-month-old African children. Sera with active complement from 100 unvaccinated blood donors were tested for intrinsic bactericidal activity, SBA titer using rabbit complement (rSBA), and anti-group A PS antibody concentration. Performance criteria and pooling strategies were examined and then verified by comparisons of three independently prepared hC' lots in two laboratories. hSBA titers of clinical trial sera were then determined using this complement sourcing method. Two different functional antibody tests were necessary for screening hC'. hSBA titers determined using three independent lots of pooled hC' were within expected assay variation among lots and between laboratories. In African toddlers, PsA-TT elicited higher hSBA titers than meningococcal polysaccharide or Hib vaccines. PsA-TT immunization or PS challenge of PsA-TT-primed subjects resulted in vigorous hSBA memory responses, and titers persisted in boosted groups for over a year. Quantifying SBA using pooled hC' is feasible and showed that PsA-TT was highly immunogenic in African toddlers. C1 [Bash, Margaret C.; Lynn, Freyja; Mocca, Brian] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Borrow, Ray; Findlow, Helen] Manchester Royal Infirm, Vaccine Evaluat Unit, Publ Hlth England, Manchester M13 9WL, Lancs, England. [Hassan-King, Musa; Preziosi, Marie-Pierre; LaForcec, F. Marc] PATH, Meningitis Vaccine Project, Ferney Voltaire, France. [Preziosi, Marie-Pierre] WHO, Meningitis Vaccine Project, Initiat Vaccine Res, CH-1211 Geneva, Switzerland. [Idoko, Olubukola] MRC, Basse, Gambia. [Sow, Samba] Ctr Dev Vaccins, Bamako, Mali. [Kulkarni, Prasad] Serum Inst India, Pune, Maharashtra, India. RP Bash, MC (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM margaret.bash@fda.hhs.gov FU PATH; World Health Organization; Bill & Melinda Gates Foundation; Pfizer; Novartis Vaccines; Baxter Bioscience; GlaxoSmithKline; Sanofi Pasteur; Merck FX This study was funded in part by the Meningitis Vaccine Project, a partnership between PATH and the World Health Organization (http: //www.meningvax.org/) supported by a grant from the Bill & Melinda Gates Foundation.; Helen Findlow has received assistance to attend scientific meetings from Baxter Bioscience. Ray Borrow and Helen Findlow have performed contract research on behalf of Public Health England (funded by Pfizer, Novartis Vaccines, Baxter Bioscience, GlaxoSmithKline, Sanofi Pasteur, and Merck). Prasad Kulkarni is employed by Serum Institute of India Ltd., the manufacturer of the study vaccine. F. Marc LaForce has received honoraria and research support from Merck for earlier work on pneumococcal polysaccharide vaccine. The remaining authors have no conflicts to declare. NR 23 TC 4 Z9 4 U1 4 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2014 VL 21 IS 5 BP 755 EP 761 DI 10.1128/CVI.00812-13 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AJ0NU UT WOS:000337352300020 PM 24671551 ER PT J AU Van Buskirk, GA Shah, V Yacobi, A Bolger, MB Chittenden, J Davit, BM DeStefano, A Dressman, J Duan, JZ Ganes, DA Gonzalez, MA Gray, V Kakhi, M Li, R Mirza, T Polli, JE Rackley, RJ Smith, DF Shephard, T Stippler, E Suarez-Sharp, S Turner, D AF Van Buskirk, Glenn A. Shah, Vinod Yacobi, Avi Bolger, Michael B. Chittenden, Jason Davit, Barbara M. DeStefano, Anthony Dressman, Jennifer Duan, John Z. Ganes, Derek A. Gonzalez, Mario A. Gray, Vivian Kakhi, Maziar Li, Rong Mirza, Tasheen Polli, James E. Rackley, Russell J. Smith, Douglas F. Shephard, Theresa Stippler, Erika Suarez-Sharp, Sandra Turner, David TI PQRI Workshop Report: Application of IVIVC in Formulation Development SO DISSOLUTION TECHNOLOGIES LA English DT Article AB This article summarizes the proceeding of the September 2012 Workshop on Application of In vitro In vivo correlation (IVIVC) in Formulation Development. The workshop brought together international experts with the goal of establishing common concepts that could be utilized to facilitate the development and validation of IVIVCs in the registration of and post-approval changes to oral solid dosage forms. The workshop was organized by the Product Quality Research Institute (PORI) and cosponsored by AAPS, FDA, FIP, and USP. Open access of this information is available to all interested parties. C1 [Van Buskirk, Glenn A.] Nonclin Drug Dev Consulting Serv LLC, Basking Ridge, NJ 07920 USA. [Yacobi, Avi] DOLE Pharma LLC, Englewood, NJ 07631 USA. [Bolger, Michael B.] Simulat Plus Inc, Lancaster, CA 93534 USA. [Chittenden, Jason] Pharsight Certara Co, St Louis, MO 63101 USA. [Davit, Barbara M.; Duan, John Z.; Kakhi, Maziar; Mirza, Tasheen; Suarez-Sharp, Sandra] Food & Drug Adm, Silver Spring, MD 20993 USA. [DeStefano, Anthony] YourEncore, Gaithersburg, MD 20882 USA. [Dressman, Jennifer] Goethe Univ Frankfurt, D-60438 Frankfurt, Germany. [Ganes, Derek A.] Ganes Pharma Inc, Toronto, ON M2N 4B4, Canada. [Gonzalez, Mario A.] PKinet Int Inc, Pembroke Pines, FL 33207 USA. [Gray, Vivian] Dissolut Technol, Hockessin, DE 19707 USA. [Li, Rong] Pfizer Inc, Groton, CT 06340 USA. [Polli, James E.] Univ Maryland, Baltimore, MD 21201 USA. [Rackley, Russell J.] Mylan Pharmaceut, Morgantown, WV 26505 USA. [Smith, Douglas F.] DFS Consulting LLC, Tucson, AZ 85718 USA. [Shephard, Theresa] Med & Healthcare Prod Regulatory Agcy MHRA, London SW 1W9SZ, England. [Stippler, Erika] United States Pharmacopeia, Rockville, MD 20852 USA. [Turner, David] SimCYP, Sheffield S24 SU, S Yorkshire, England. RP Van Buskirk, GA (reprint author), Nonclin Drug Dev Consulting Serv LLC, Basking Ridge, NJ 07920 USA. EM vanbuskirk@drugdevconsult.com RI Bolger, Michael/I-5931-2015; Fachbereich14, Dekanat/C-8553-2015 OI Bolger, Michael/0000-0002-6992-3036; NR 7 TC 1 Z9 1 U1 0 U2 3 PU DISSOLUTION TECHNOLOGIES, INC PI HOCKESSIN PA 9 YORKRIDGE TRAIL, HOCKESSIN, DE 19707-9633 USA SN 1521-298X J9 DISSOLUT TECHNOL JI Dissolut. Technol. PD MAY PY 2014 VL 21 IS 2 BP 51 EP 58 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ4RK UT WOS:000337663300007 ER PT J AU Krishnaiah, YSR Katragadda, U Khan, MA AF Krishnaiah, Yellela S. R. Katragadda, Usha Khan, Mansoor A. TI Stereomicroscopic Imaging Technique for the Quantification of Cold Flow in Drug-in-Adhesive Type of Transdermal Drug Delivery Systems SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE transdermal; skin; drug delivery systems; microscopy; cold flow; stereomicroscopic; method development; imaging; drug-in-adhesive; physical characterization ID PRESSURE-SENSITIVE ADHESIVE; PATCHES AB Cold flowis a phenomenon occurring in drug-in-adhesive type of transdermal drug delivery systems (DIA-TDDS) because of the migration of DIA coat beyond the edge. Excessive cold flow can affect their therapeutic effectiveness, make removal of DIA-TDDS difficult from the pouch, and potentially decrease available dose if any drug remains adhered to pouch. There are no compendial or noncompendial methods available for quantification of this critical quality attribute. The objective was to develop a method for quantification of cold flow using stereomicroscopic imaging technique. Cold flow was induced by applying 1 kg force on punched-out samples of marketed estradiol DIA-TDDS (model product) stored at 25 degrees C, 32 degrees C, and 40 degrees C/60% relative humidity (RH) for 1, 2, or 3 days. At the end of testing period, dimensional change in the area of DIA-TDDS samples was measured using image analysis software, and expressed as percent of cold flow. The percent of cold flow significantly decreased (p < 0.001) with increase in size of punched-out DIA-TDDS samples and increased (p < 0.001) with increase in cold flow induction temperature and time. This first ever report suggests that dimensional change in the area of punched-out samples stored at 32 degrees C/60% RH for 2 days applied with 1 kg force could be used for quantification of cold flow in DIA-TDDS. (C) 2014 Wiley Periodicals, Inc. C1 [Krishnaiah, Yellela S. R.; Katragadda, Usha; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Krishnaiah, YSR (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM krishnaiah.yellela@fda.hhs.gov FU Office of Women's Health, US FDA [750312CDR] FX This part of the research work was funded by Office of Women's Health, US FDA (Grant ID: 750312CDR). The comments from CDER's Transdermal Working Group are gratefully acknowledged. NR 23 TC 1 Z9 1 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 EI 1520-6017 J9 J PHARM SCI-US JI J. Pharm. Sci. PD MAY PY 2014 VL 103 IS 5 BP 1433 EP 1442 DI 10.1002/jps.23915 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA AJ4TE UT WOS:000337668300002 PM 24585397 ER PT J AU Li, PJ Marino, M Reiser, J AF Li, Pingjuan Marino, Michael Reiser, Jakob TI Targeted Lentiviral Vector Integration at "Safe Harbor" Genomic loci SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Li, Pingjuan; Marino, Michael; Reiser, Jakob] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 97 BP S36 EP S37 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300097 ER PT J AU Lynch, PJ Gonzalez, YIR Hursh, D AF Lynch, Patrick J. Gonzalez, Yazmin I. Rovira Hursh, Deborah TI Dynamics of Histone Modifications at the Cytokine-Inducible Promoters for IDO1 and TSG-6 in Human Bone-Marrow Derived MSCs SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Lynch, Patrick J.] US FDA, Div Cell & Gene Therapy, Ceter Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 480 BP S184 EP S184 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300475 ER PT J AU Marino, MP Ou, W Panigaj, M Reiser, J AF Marino, Michael P. Ou, Wu Panigaj, Martin Reiser, Jakob TI A Simple and Scalable Method to Concentrate Measles-Pseudotyped Lentiviral Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Marino, Michael P.; Ou, Wu; Panigaj, Martin; Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RI Panigaj, Martin/G-6492-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 547 BP S213 EP S213 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300542 ER PT J AU Ou, W Suzuki, A Marino, MP Li, PJ Joshi, B Husain, SR Puri, RK Reiser, J AF Ou, Wu Suzuki, Akiko Marino, Michael P. Li, Pingjuan Joshi, Bharat Husain, Syred R. Puri, Raj K. Reiser, Jakob TI Developing Lentiviral Vectors for Targeted Gene Delivery In Vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Ou, Wu; Suzuki, Akiko; Marino, Michael P.; Li, Pingjuan; Joshi, Bharat; Husain, Syred R.; Puri, Raj K.; Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 59 BP S23 EP S23 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300059 ER PT J AU Panigaj, M Marino, M Reiser, J AF Panigaj, Martin Marino, Michael Reiser, Jakob TI Cell-Specific Targeting of Lentiviral Vectors Mediated by RNA Aptamers SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Panigaj, Martin; Marino, Michael; Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RI Panigaj, Martin/G-6492-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 52 BP S21 EP S21 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300053 ER PT J AU Qiu, Q Xu, ZL Tian, J Moitra, R Byrnes, AP AF Qiu, Qi Xu, Zhili Tian, Jie Moitra, Rituparna Byrnes, Andrew P. TI Natural Antibodies Inhibit Liver Transduction with Adenovirus Vectors in Mice SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Qiu, Qi; Xu, Zhili; Tian, Jie; Moitra, Rituparna; Byrnes, Andrew P.] US FDA, Div Cellular & Gene Therapies, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 308 BP S118 EP S118 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300308 ER PT J AU Tian, J Moitra, R Xu, ZL Qiu, Q Palmer, DJ Ng, P Byrnes, AP AF Tian, Jie Moitra, Rituparna Xu, Zhili Qiu, Qi Palmer, Donna J. Ng, Philip Byrnes, Andrew P. TI Variations in Liver Transduction Ability Among Species C Adenovirus Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Tian, Jie; Moitra, Rituparna; Xu, Zhili; Qiu, Qi; Byrnes, Andrew P.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Palmer, Donna J.; Ng, Philip] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 314 BP S121 EP S121 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300314 ER PT J AU Liu, F Rainosek, SW Sadovova, N Fogle, CM Patterson, TA Hanig, JP Paule, MG Slikker, W Wang, C AF Liu, Fang Rainosek, Shuo W. Sadovova, Natalya Fogle, Charles M. Patterson, Tucker A. Hanig, Joseph P. Paule, Merle G. Slikker, William, Jr. Wang, Cheng TI Protective effect of acetyl-L-carnitine on propofol-induced toxicity in embryonic neural stem cells SO NEUROTOXICOLOGY LA English DT Article DE Neural stem cells; Propofol; Apoptosis; Protection ID RAT FOREBRAIN CULTURE; D-ASPARTATE RECEPTOR; MITOCHONDRIAL-DNA; NEUROLOGICAL SEQUELAE; ALZHEIMERS-DISEASE; EXCITATORY ACTIONS; INDUCED APOPTOSIS; CORTICAL-NEURONS; OXIDATIVE STRESS; BRAIN AB Propofol is a widely used general anesthetic. A growing body of data suggests that perinatal exposure to general anesthetics can result in long-term deleterious effects on brain function. In the developing brain there is evidence that general anesthetics can cause cell death, synaptic remodeling, and altered brain cell morphology. Acetyl-L-carnitine (L-Ca), an anti-oxidant dietary supplement, has been reported to prevent neuronal damage from a variety of causes. To evaluate the ability of L-Ca to protect against propofol-induced neuronal toxicity, neural stem cells were isolated from gestational day 14 rat fetuses and on the eighth day in culture were exposed for 24 h to propofol at 10, 50, 100,300 and 600 mu M, with or without L-Ca (10 mu M). Markers of cellular proliferation, mitochondrial health, cell death/damage and oxidative damage were monitored to determine: (1) the effects of propofol on neural stem cell proliferation; (2) the nature of propofol-induced neurotoxicity; (3) the degree of protection afforded by L-Ca; and (4) to provide information regarding possible mechanisms underlying protection. After propofol exposure at a clinically relevant concentration (50 mu M), the number of dividing cells was significantly decreased, oxidative DNA damage was increased and a significant dose-dependent reduction in mitochondrial function/health was observed. No significant effect on lactase dehydrogenase (LDH) release was observed at propofol concentrations up to 100 mu M. The oxidative damage at 50 mu M propofol was blocked by L-Ca. Thus, clinically relevant concentrations of propofol induce dose-dependent adverse effects on rat embryonic neural stem cells by slowing or stopping cell division/proliferation and causing cellular damage. Elevated levels of 8-oxoguanine suggest enhanced oxidative damage [reactive oxygen species (ROS) generation] and L-Ca effectively blocks at least some of the toxicity of propofol, presumably by scavenging oxidative species and/or reducing their production. Published by Elsevier Inc. C1 [Liu, Fang; Fogle, Charles M.; Patterson, Tucker A.; Paule, Merle G.; Wang, Cheng] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Rainosek, Shuo W.] Univ Arkansas Med Sci, Dept Anesthesiol, Little Rock, AR 72205 USA. [Sadovova, Natalya] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Hanig, Joseph P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Slikker, William, Jr.] US FDA, Off Director, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Liu, F (reprint author), US FDA, Natl Ctr Toxicol Res, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Fang.liu@fda.hhs.gov; Cheng.wang@fda.hhs.gov NR 52 TC 10 Z9 14 U1 3 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAY PY 2014 VL 42 BP 49 EP 57 DI 10.1016/j.neuro.2014.03.011 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA AJ4QW UT WOS:000337661900006 PM 24704589 ER PT J AU Battistel, MD Azurmendi, HF Yu, B Freedberg, DI AF Battistel, Marcos D. Azurmendi, Hugo F. Yu, Bingwu Freedberg, Daron I. TI NMR of glycans: Shedding new light on old problems SO PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY LA English DT Review DE Glycan NMR; Hydroxyl groups; Hydrogen bonds; Isotopic labeling and 3D Structure; Residual dipolar coupling ID RESIDUAL DIPOLAR COUPLINGS; NUCLEAR-MAGNETIC-RESONANCE; HYDROXYMETHYL GROUP CONFORMATION; INTRAMOLECULAR HYDROGEN-BONDS; LIQUID-CRYSTALLINE MEDIUM; MODEL-FREE APPROACH; AQUEOUS-SOLUTION; NATURAL-ABUNDANCE; CHEMICAL-SHIFTS; 3-DIMENSIONAL STRUCTURES AB The diversity in molecular arrangements and dynamics displayed by glycans renders traditional NMR strategies, employed for proteins and nucleic acids, insufficient. Because of the unique properties of glycans, structural studies often require the adoption of a different repertoire of tailor-made experiments and protocols. We present an account of recent developments in NMR techniques that will deepen our understanding of structure-function relations in glycans. We open with a survey and comparison of methods utilized to determine the structure of proteins, nucleic acids and carbohydrates. Next, we discuss the structural information obtained from traditional NMR techniques like chemical shifts, NOEs/ROEs, and coupling-constants, along with the limitations imposed by the unique intrinsic characteristics of glycan structure on these approaches: flexibility, range of conformers, signal overlap, and non-first-order scalar (strong) coupling. Novel experiments taking advantage of isotopic labeling are presented as an option for overcoming spectral overlap and raising sensitivity. Computational tools used to explore conformational averaging in conjunction with NMR parameters are described. In addition, recent developments in hydroxyl detection and hydrogen bond detection in protonated solvents, in contrast to traditional sample preparations in D2O for carbohydrates, further increase the tools available for both structure information and chemical shift assignments. We also include previously unpublished data in this context. Accurate determination of couplings in carbohydrates has been historically challenging due to the common presence of strong-couplings. We present new strategies proposed for dealing with their influence on NMR signals. We close with a discussion of residual dipolar couplings (RDCs) and the advantages of using C-13 isotope labeling that allows gathering one-bond C-13-C-13 couplings with a recently improved constant-time COSY technique, in addition to the commonly measured H-1-C-13 RDCs. Published by Elsevier B.V. C1 [Battistel, Marcos D.; Azurmendi, Hugo F.; Yu, Bingwu; Freedberg, Daron I.] US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Freedberg, DI (reprint author), US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM daron.freedberg@fda.hhs.gov NR 169 TC 9 Z9 9 U1 6 U2 54 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6565 J9 PROG NUCL MAG RES SP JI Prog. Nucl. Magn. Reson. Spectrosc. PD MAY PY 2014 VL 79 BP 48 EP 68 DI 10.1016/j.pnmrs.2014.01.001 PG 21 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Chemistry; Physics; Spectroscopy GA AJ4NE UT WOS:000337652300003 PM 24815364 ER PT J AU Tallent, SM Hait, J Bennett, RW AF Tallent, Sandra M. Hait, Jennifer Bennett, Reginald W. TI Staphylococcal Enterotoxin B-Specific Electrochemiluminescence and Lateral Flow Device Assays Cross-React with Staphylococcal Enterotoxin D SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FOODBORNE ILLNESS AB Guam school children and faculty members experienced symptoms of vomiting, nausea, abdominal cramps, and diarrhea shortly after eating breakfast prepared by contracted caterers. The first illness was reported within an hour after breakfast, affecting 295 students and two faculty members. Local hospitals treated 130 people, and 61 were admitted for further treatment. Reported symptoms were consistent with staphylococcal food poisoning. Initial food testing using a lateral flow device and electrochemiluminescence method incorrectly implicated staphylococcal enterotoxin B as the causative agent, prompting partial activation of Guam's Emergency Response Center. Traditional ELISAs proved that the food poisoning agent was staphylococcal enterotoxin D. More specific and sensitive assays would have alleviated the issues and confusion that surrounded the reporting and investigation of this outbreak. C1 [Tallent, Sandra M.; Hait, Jennifer; Bennett, Reginald W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Tallent, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM sandra.tallent@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases/National Institutes of Health [HHSN272200700055C] FX Isolates were obtained through the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA, Chantilly, VA) Program NRS100 supported under the National Institute of Allergy and Infectious Diseases/National Institutes of Health Contract No. HHSN272200700055C. We would like to thank all the local, state, and federal officials who participated in this investigation, and we thank Lili Velez, FDA, CFSAN, for her review of this manuscript. NR 15 TC 1 Z9 1 U1 2 U2 4 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2014 VL 97 IS 3 BP 862 EP 867 DI 10.5740/jaoacint.13-198 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA AI8ZT UT WOS:000337216200027 PM 25051635 ER PT J AU Zhang, K Wong, JW Jia, ZW Vaclavikova, M Trucksess, MW Begley, TH AF Zhang, Kai Wong, Jon W. Jia, Zhengwei Vaclavikova, Marta Trucksess, Mary W. Begley, Timothy H. TI Screening Multimycotoxins in Food-Grade Gums by Stable Isotope Dilution and Liquid Chromatography/Tandem Mass Spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MULTI-MYCOTOXIN ANALYSIS; ASSAY; CORN; IDENTIFICATION; CONFIRMATION; PESTICIDES; AFLATOXINS; PRODUCTS; PEANUTS; FEED AB Stable isotope dilution with LC/MS/MS was used to determine the following 11 mycotoxins in food grade gums: aflatoxins B-1, B-2, G(1), and G(2); deoxynivalenol; fumonisins B-1, B-2, and B-3; ochratoxin A; T-2 toxin; and zearalenone. Samples were fortified with 11 [C-13]-uniformly labeled internal standard ([C-13]-IS) mycotoxins that corresponded to the 11 target mycotoxins and extracted by acetonitrile-water (4 + 1, v/v), followed by LC/MS/MS analysis. Mycotoxins were quantitated with the fortified (C-13]-IS in each sample. The average recoveries of aflatoxins B-1, B-2, G(1), and G(2) (1, 5, and 25 mu g/kg); deoxynivalenol and fumonisins B-1, B-2, and B-3 (25, 100, and 500 mu g/kg); and ochratoxin A, T-2 toxin, and zearalenone (10, 50, and 250 mu g/kg) ranged from 84 to 117% with RSDs less than 20%. Method-dependent LOQs were from 0.1 (aflatoxin B-1) to 25 mu g/kg (fumonisin B-3). Among 20 market samples, aflatoxin B-1 (= 70% of the observed results when the conventional "twofold rule" and the more conservative 25% deviation cut point were applied, respectively. These findings suggest that PBPK models can be used to infer effects of individual or combined IEFs and should be considered to optimize studies that evaluate these factors, specifically drug interactions and genetic polymorphism of drug-metabolizing enzymes. C1 [Vieira, Md L. T.; Kim, M-J; Apparaju, S.; Sinha, V.; Zineh, I.; Huang, S-M; Zhao, P.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zhao, P (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM ping.zhao@fda.hhs.gov NR 41 TC 15 Z9 16 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2014 VL 95 IS 5 BP 550 EP 557 DI 10.1038/clpt.2014.43 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF5NJ UT WOS:000334759900027 PM 24556783 ER PT J AU Wang, J Song, P Schrieber, S Liu, Q Xu, Q Blumenthal, G Kordestani, LA Cortazar, P Ibrahim, A Justice, R Wang, Y Tang, S Booth, B Mehrotra, N Rahman, A AF Wang, J. Song, P. Schrieber, S. Liu, Q. Xu, Q. Blumenthal, G. Kordestani, L. Amiri Cortazar, P. Ibrahim, A. Justice, R. Wang, Y. Tang, S. Booth, B. Mehrotra, N. Rahman, A. TI Exposure-Response Relationship of T-DM1: Insight Into Dose Optimization for Patients With HER2-Positive Metastatic Breast Cancer SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; TRASTUZUMAB EMTANSINE; PHASE-II; PHARMACOKINETICS; ASSOCIATION; RECURRENT; IMATINIB; TUMORS AB Exposure-response (E-R) analyses for ado-trastuzumab emtansine (T-DM1, Kadcyla) were performed using data from a randomized, active control (lapatinib plus capecitabine) trial in patients with human epidermal growth factor 2-positive metastatic breast cancer. Kaplan-Meier survival analyses stratified by T-DM1 trough concentration on day 21 of cycle 1(C-min,C-C1D21) were performed for overall survival (OS) and progression-free survival (PFS). E-R analyses indicated that after adjusting for baseline risk factors, higher T-DM1 exposure is associated with improved efficacy. T-DM1-treated patients with C-min,C-C1D21 lower than the median value had values of OS and PFS comparable to those of the active control arm. The percentage of patients who received T-DM1 dose adjustments was similar across the exposure range and was lower than that of the active control arm. Our findings suggest that there may be an opportunity to optimize Kadcyla dose in the patient subgroup with low T-DM1 exposure for improved efficacy with acceptable tolerability. C1 [Wang, J.; Song, P.; Schrieber, S.; Liu, Q.; Wang, Y.; Booth, B.; Mehrotra, N.; Rahman, A.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Xu, Q.; Tang, S.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Blumenthal, G.; Kordestani, L. Amiri; Cortazar, P.; Ibrahim, A.; Justice, R.] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Wang, J (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM jian.wang@fda.hhs.gov NR 30 TC 8 Z9 8 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2014 VL 95 IS 5 BP 558 EP 564 DI 10.1038/clpt.2014.24 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF5NJ UT WOS:000334759900028 PM 24488143 ER PT J AU Hampp, C Borders-Hemphill, V Moeny, DG Wysowski, DK AF Hampp, Christian Borders-Hemphill, Vicky Moeny, David G. Wysowski, Diane K. TI Use of Antidiabetic Drugs in the U. S., 2003-2012 SO DIABETES CARE LA English DT Article ID BARIATRIC SURGERY; METFORMIN THERAPY; DIABETES-MELLITUS; MEDICAL THERAPY; ROSIGLITAZONE; SAFETY; TRENDS; RISK; PATTERNS; CARE AB OBJECTIVETo describe market trends for antidiabetic drugs, focusing on newly approved drugs, concomitant use of antidiabetic drugs, and effects of safety concerns and access restrictions on thiazolidinedione use.RESEARCH DESIGN AND METHODSNationally projected data on antidiabetic prescriptions for adults dispensed from U.S. retail pharmacies were extracted from IMS Health Vector One National and Total Patient Tracker for 2003-2012 and from Encuity Research Treatment Answers and Symphony Health Solutions PHAST Prescription Monthly for 2012.RESULTSSince 2003, the number of adult antidiabetic drug users increased by 42.9% to 18.8 million in 2012. Metformin use increased by 97.0% to 60.4 million prescriptions dispensed in retail pharmacies in 2012. Among antidiabetic drugs newly approved for marketing between 2003 and 2012, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin had the largest share with 10.5 million prescriptions in 2012. Rosiglitazone use plummeted to <13,000 prescriptions dispensed in retail or mail-order pharmacies in 2012. Concomitancy analyses showed that 44.9% of metformin use was for monotherapy. Between 33.4 and 48.1% of sulfonylurea, DPP-4 inhibitor, thiazolidinedione, and glucagon-like peptide 1 analog use was not accompanied by metformin.CONCLUSIONSThe antidiabetic drug market is characterized by steady increases in volume, and newly approved drugs experienced substantial uptake, especially DPP-4 inhibitors. The use of rosiglitazone has been negligible since restrictions were put in place in 2011. Further study is needed to understand why one-third to one-half of other noninsulin antidiabetic drug use was not concomitant with metformin use despite guidelines recommending that metformin be continued when other agents are added to treatment. C1 [Hampp, Christian; Wysowski, Diane K.] US FDA, Div Epidemiol 1, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD 20993 USA. [Borders-Hemphill, Vicky] US FDA, Div Medicat Error Prevent & Anal, Off Medicat Error Prevent & Risk Management, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD USA. [Moeny, David G.] US FDA, Div Epidemiol 2, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD USA. RP Hampp, C (reprint author), US FDA, Div Epidemiol 1, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD 20993 USA. EM christian.hampp@fda.hhs.gov OI Hampp, Christian/0000-0002-1094-6364 NR 36 TC 56 Z9 56 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2014 VL 37 IS 5 BP 1367 EP 1374 DI 10.2337/dc13-2289 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AF6QQ UT WOS:000334840100052 PM 24623020 ER PT J AU Trickler, WJ Lantz-McPeak, SM Robinson, BL Paule, MG Slikker, W Biris, AS Schlager, JJ Hussain, SM Kanungo, J Gonzalez, C Ali, SF AF Trickler, William J. Lantz-McPeak, Susan M. Robinson, Bonnie L. Paule, Merle G. Slikker, William, Jr. Biris, Alexandru S. Schlager, John J. Hussain, Saber M. Kanungo, Jyotshna Gonzalez, Carmen Ali, Syed F. TI Porcine brain microvessel endothelial cells show pro-inflammatory response to the size and composition of metallic nanoparticles SO DRUG METABOLISM REVIEWS LA English DT Review DE Blood-brain barrier; lipopolysaccharide (LPS); metallic-colloidal nanoparticles; neuroinflamation; neurotoxicity; porcine brain microvessel endothelial cells ID NECROSIS-FACTOR-ALPHA; BARRIER IN-VITRO; SILVER NANOPARTICLES; TNF-ALPHA; PERMEABILITY; MODEL; EXPOSURE; RELEASE; RAT; ENCEPHALOPATHY AB The purpose of the current studies was to determine if systemic exposure of various metallic nanoparticles differing in size and composition [silver (Ag-NPs, 25, 40 and 80 nm), copper-oxide (Cu-NPs, 40 and 60 nm) or gold (Au-NPs, 3 and 5 nm)] can induce the release of pro-inflammatory mediators that influence the restrictive nature of the blood-brain barrier (BBB) in vitro. Confluent porcine brain microvessel endothelial cells (pBMECs) (8-12 days) were treated with various metallic nanoparticles (15 mg/ml). Extracellular concentrations of pro-inflammatory mediators (IL-1 beta, TNF alpha and PGE(2)) were evaluated using ELISA. pBMECs were cultured in standard 12-well Transwell (R) inserts, and permeability was evaluated by measuring the transport of fluorescein across the pBMEC monolayers. PGE(2) release following Cu-NP exposure was significantly increased when compared to the control. Similar results were observed for Ag-NPs but not Au-NPs. The secretion of TNF alpha and IL-1 beta was observed for both Cu-NPs and Ag-NPs but not in response to Au-NPs. The post-treatment time profiles of TNF alpha and IL-1 beta revealed that the IL-1 beta response was more persistent. The permeability ratios (exposure/control) were significantly greater following exposure to Cu-NPs or Ag-NPs, compared to Au-NPs. Together, these data suggest that the composition and size of NPs can cause significant pro-inflammatory response that can influence the integrity of the BBB. C1 [Trickler, William J.; Lantz-McPeak, Susan M.; Robinson, Bonnie L.; Paule, Merle G.; Slikker, William, Jr.; Kanungo, Jyotshna; Ali, Syed F.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. [Schlager, John J.; Hussain, Saber M.] Air Force Res Lab, Appl Biotechnol Branch, Human Effectiveness Directorate, Wright Patterson AFB, OH USA. [Gonzalez, Carmen] Univ Autonoma San Luis Potosi, Fac Ciencias Quim, Lab Fisiol Celular, San Luis Potosi, Mexico. RP Ali, SF (reprint author), US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM syed.ali@fda.hhs.gov NR 43 TC 9 Z9 9 U1 1 U2 18 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PD MAY PY 2014 VL 46 IS 2 BP 224 EP 231 DI 10.3109/03602532.2013.873450 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF8BJ UT WOS:000334939700008 PM 24378227 ER PT J AU Zhang, YB Petibone, D Xu, Y Mahmood, M Karmakar, A Casciano, D Ali, S Biris, AS AF Zhang, Yongbin Petibone, Dayton Xu, Yang Mahmood, Meena Karmakar, Alokita Casciano, Dan Ali, Syed Biris, Alexandru S. TI Toxicity and efficacy of carbon nanotubes and graphene: the utility of carbon-based nanoparticles in nanomedicine SO DRUG METABOLISM REVIEWS LA English DT Review DE Biological behavior; carbon-based nanomaterials; nanotherapy; ROS; toxicokinetics ID NEAR-INFRARED AGENTS; IN-VITRO; BIOMEDICAL APPLICATIONS; OXIDATIVE STRESS; DRUG-DELIVERY; CANCER-CELLS; STEM-CELLS; SYNERGISTIC ENHANCEMENT; PULMONARY TOXICITY; EPITHELIAL-CELLS AB Carbon-based nanomaterials have attracted great interest in biomedical applications such as advanced imaging, tissue regeneration, and drug or gene delivery. The toxicity of the carbon nanotubes and graphene remains a debated issue although many toxicological studies have been reported in the scientific community. In this review, we summarize the biological effects of carbon nanotubes and graphene in terms of in vitro and in vivo toxicity, genotoxicity and toxicokinetics. The dose, shape, surface chemistry, exposure route and purity play important roles in the metabolism of carbon-based nanomaterials resulting in differential toxicity. Careful examination of the physico-chemical properties of carbon-based nanomaterials is considered a basic approach to correlate the toxicological response with the unique properties of the carbon nanomaterials. The reactive oxygen species-mediated toxic mechanism of carbon nanotubes has been extensively discussed and strategies, such as surface modification, have been proposed to reduce the toxicity of these materials. Carbon-based nanomaterials used in photothermal therapy, drug delivery and tissue regeneration are also discussed in this review. The toxicokinetics, toxicity and efficacy of carbon-based nanotubes and graphene still need to be investigated further to pave a way for biomedical applications and a better understanding of their potential applications to humans. C1 [Zhang, Yongbin] US FDA, Nanotechnol Core Facil, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Petibone, Dayton] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Xu, Yang; Mahmood, Meena; Karmakar, Alokita; Casciano, Dan; Biris, Alexandru S.] Univ Arkansas, Ctr Integrat Nanotechnol Sci, Little Rock, AR 72204 USA. [Ali, Syed] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Biris, AS (reprint author), Univ Arkansas, Ctr Integrat Nanotechnol Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM asbiris@ualr.edu NR 99 TC 33 Z9 34 U1 10 U2 153 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PD MAY PY 2014 VL 46 IS 2 BP 232 EP 246 DI 10.3109/03602532.2014.883406 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF8BJ UT WOS:000334939700009 PM 24506522 ER PT J AU Slayton, RB Newton, AE Depaola, A Jones, JL Mahon, BE AF Slayton, R. B. Newton, A. E. Depaola, A. Jones, J. L. Mahon, B. E. TI Clam-associated vibriosis, USA, 1988-2010 SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Clams; epidemiology; shellfish; Vibrionaceae; vulnificus ID RAW OYSTERS; UNITED-STATES; VULNIFICUS; PARAHAEMOLYTICUS; SEPTICEMIA; PATHOGENS AB Infections with Vibrio spp. have frequently been associated with consumption of bivalve molluscs, especially oysters, but illness associated with clams has also been well documented. We describe the 2312 domestically acquired foodborne Vibrio infections reported to the Cholera and Other Vibrio Illness Surveillance system from 1988 to 2010. Clams were associated with at least 4% (93 persons, only clams') and possibly as many as 24% (556 persons, any clams') of foodborne cases. Of those who consumed only clams', 77% of infections were caused by V. parahaemolyticus. Clam-associated illnesses were generally similar to those associated with other seafood consumption. Clams associated with these illnesses were most frequently harvested from the Atlantic coastal states and eaten raw. Our study describes the contribution of clams to the overall burden of foodborne vibriosis and indicates that a comprehensive programme to prevent foodborne vibriosis need to address the risks associated with clams. C1 [Slayton, R. B.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Slayton, R. B.; Newton, A. E.; Mahon, B. E.] Ctr Dis Control & Prevent, Enter Dis Epidemiol Branch, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA. [Depaola, A.; Jones, J. L.] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. RP Slayton, RB (reprint author), US Ctr Dis Control & Prevent, 1600 Clifton Rd,MS A-31, Atlanta, GA 30333 USA. EM via3@cdc.gov OI Slayton, Rachel/0000-0003-4699-8040 FU Intramural CDC HHS [CC999999] NR 17 TC 5 Z9 5 U1 0 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 EI 1469-4409 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD MAY PY 2014 VL 142 IS 5 BP 1083 EP 1088 DI 10.1017/S0950268813001830 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AD9BZ UT WOS:000333560900021 PM 23920418 ER PT J AU Toomer, OT Ferguson, M Pereira, M Do, A Bigley, E Gaines, D Williams, K AF Toomer, Ondulla T. Ferguson, Martine Pereira, Marion Do, Andrew Bigley, Elmer Gaines, Dennis Williams, Kristina TI Maternal and postnatal dietary probiotic supplementation enhances splenic regulatory T helper cell population and reduces ovalbumin allergen-induced hypersensitivity responses in mice SO IMMUNOBIOLOGY LA English DT Article DE Food allergy; Mouse; Ovalbumin; Probiotics ID PLACEBO-CONTROLLED TRIAL; BLOOD MONONUCLEAR-CELLS; IMMUNE-RESPONSES; HUMAN-MILK; ENVIRONMENTAL ALLERGENS; ESCHERICHIA-COLI; CYTOKINE PROFILE; FOOD ALLERGY; DOUBLE-BLIND; MOUSE MODEL AB Neonatal to early childhood is the critical period for establishing a balance of T helper 1 (Th1) versus T helper 2 (Th2) cellular immunity within the gut, which is strongly influenced by the source and establishment of gut microflora. Probiotic administration has been shown to attenuate Th2-biased cellular immunity and predisposition to food allergies. To test this hypothesis we provided ad libitum a probiotic-supplemented (Primalac 454 Feed Grade Microbials) or control diet to lactating dams with suckling pups and weaned pups until 10 weeks of age. Weaned mice were sensitized/challenged with egg allergen ovalbumin, saline or adjuvant at 6, 8 and 10 weeks of age. At 3, 6, 8 and 10 weeks, fecal samples were collected for microbial analysis, while blood samples were analyzed for ovalbumin-IgE and total plasma IgE levels. At termination, splenic T helper cell lymphocyte population subtypes were determined using FACS analysis and Th1/Th2/Th17 gene expression by PCR array. At 21 days of age, pups suckled by lactating dams fed the probiotic supplemented diet had significantly enhanced Lactobacillus acidophilus fecal counts compared to controls. Moreover, mice fed the probiotic supplemented diet had enhanced splenic naturally occurring and induced regulatory T cell populations, enhanced TGF beta gene expression and reduced expression of allergic mediator IL13 compared to controls. These results provide evidence that early probiotic supplementation may provide host protection from hypersensitivity reactions to food allergens by attenuating food allergen inflammatory responses. Published by Elsevier GmbH. C1 [Toomer, Ondulla T.; Ferguson, Martine; Pereira, Marion; Do, Andrew; Bigley, Elmer; Gaines, Dennis; Williams, Kristina] US FDA, Laurel, MD 20708 USA. RP Toomer, OT (reprint author), US FDA, Immunobiol Branch, Div Virulence Assessment, Off Appl Res & Safety Assessment,Ctr Food Safety, 8301 Muirkirk Rd,MOD 1,Room 2007, Laurel, MD 20708 USA. EM Ondulla.Toomer@fda.hhs.gov NR 50 TC 7 Z9 10 U1 1 U2 12 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD MAY PY 2014 VL 219 IS 5 BP 367 EP 376 DI 10.1016/j.imbio.2014.01.003 PG 10 WC Immunology SC Immunology GA AF1NJ UT WOS:000334480300005 PM 24612822 ER PT J AU Baumann, MH Bulling, S Benaderet, TS Saha, K Ayestas, MA Partilla, JS Ali, SF Stockner, T Rothman, RB Sandtner, W Sitte, HH AF Baumann, Michael H. Bulling, Simon Benaderet, Tova S. Saha, Kusumika Ayestas, Mario A. Partilla, John S. Ali, Syed F. Stockner, Thomas Rothman, Richard B. Sandtner, Walter Sitte, Harald H. TI Evidence for a Role of Transporter-Mediated Currents in the Depletion of Brain Serotonin Induced by Serotonin Transporter Substrates SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin (5-HT) release; 5-HT depletion; 5-HT transporter (SERT); SERT substrate; SERT-mediated current ID INCREASES EXTRACELLULAR SEROTONIN; PRIMARY PULMONARY-HYPERTENSION; VALVULAR HEART-DISEASE; RAT-BRAIN; D-FENFLURAMINE; P-CHLOROAMPHETAMINE; IN-VIVO; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SUBSTITUTED AMPHETAMINES; NEUROTOXICITY PROFILES AB Serotonin (5-HT) transporter (SERT) substrates like fenfluramine and 3,4-methylenedioxymethamphetamine cause long-term depletion of brain 5-HT, while certain other substrates do not. The 5-HT deficits produced by SERT substrates are dependent upon transporter proteins, but the exact mechanisms responsible are unclear. Here, we compared the pharmacology of several SERT substrates: fenfluramine, d-fenfluramine, 1-(m-chlorophenyl)piperazine (mCPP) and 1-(m-trifluoromethylphenyl)piperainze (TFMPP), to establish relationships between acute drug mechanisms and the propensity for long-term 5-HT depletions. In vivo microdialysis was carried out in rat nucleus accumbens to examine acute 5-HT release and long-term depletion in the same subjects. In vitro assays were performed to measure efflux of [H-3]5-HT in rat brain synaptosomes and transporter-mediated ionic currents in SERT-expressing Xenopus oocytes. When administered repeatedly to rats (6 mg/kg, i.p., four doses), all drugs produce large sustained elevations in extracellular 5-HT (>5-fold) with minimal effects on dopamine. Importantly, 2 weeks after dosing, only rats exposed to fenfluramine and d-fenfluramine display depletion of brain 5-HT. All test drugs evoke fluoxetine-sensitive efflux of [H-3]5-HT from synaptosomes, but d-fenfluramine and its bioactive metabolite d-norfenfluramine induce significantly greater SERT-mediated currents than phenylpiperazines. Our data confirm that drug-induced 5-HT release probably does not mediate 5-HT depletion. However, the magnitude of transporter-mediated inward current may be a critical factor in the cascade of events leading to 5-HT deficits. This hypothesis warrants further study, especially given the growing popularity of designer drugs that target SERT. C1 [Baumann, Michael H.; Benaderet, Tova S.; Ayestas, Mario A.; Partilla, John S.; Rothman, Richard B.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA. [Bulling, Simon; Saha, Kusumika; Stockner, Thomas; Sandtner, Walter; Sitte, Harald H.] Med Univ Vienna, Inst Pharmacol, Ctr Physiol & Pharmacol, A-1090 Vienna, Austria. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Sitte, HH (reprint author), Med Univ Vienna, Inst Pharmacol, Ctr Physiol & Pharmacol, Waehringerstr 13 A, A-1090 Vienna, Austria. EM harald.sitte@meduniwien.ac.at RI Stockner, Thomas/A-9509-2014; OI Stockner, Thomas/0000-0002-7071-8283; Sitte, Harald/0000-0002-1339-7444 FU Intramural Research Program of the NIDA; NIH; Austrian Research Fund/FWF [F3506, W1232]; [DA000523-05] FX This research was supported by the Intramural Research Program of the NIDA, NIH, DA000523-05 to MHB and the Austrian Research Fund/FWF grants F3506 and W1232 to HHS. We are indebted to Klaus Schicker for valuable comments on the manuscript. NR 69 TC 9 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2014 VL 39 IS 6 BP 1355 EP 1365 DI 10.1038/npp.2013.331 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AF2RV UT WOS:000334560600007 PM 24287719 ER PT J AU Mummaneni, P Shord, SS AF Mummaneni, Padmaja Shord, Stacy S. TI Epigenetics and Oncology SO PHARMACOTHERAPY LA English DT Review DE oncology; targeted therapy; epigenetics ID HISTONE DEACETYLASE INHIBITORS; DNA METHYLTRANSFERASE INHIBITORS; TUMOR-SUPPRESSOR GENES; ACUTE MYELOID-LEUKEMIA; PHASE-I TRIAL; DRUG-RESISTANCE; OVARIAN-CANCER; PROMOTER HYPERMETHYLATION; MYELODYSPLASTIC SYNDROMES; COLORECTAL-CANCER AB Epigenetic modifications play a critical role in the development of pediatric and adult cancers, contributing to the cumulative changes observed as normal cells undergo malignant transformation. These modifications have been studied to develop epigenome-targeted therapies and new diagnostic tools. The U.S. Food and Drug Administration has approved four epigenome-targeted anticancer drugs. Two are drugs that inhibit DNA methyltransferases: azacitidine and decitabine, and two are drugs that inhibit histone deacetylases: vorinostat and romidepsin. These initial successes demonstrate the potential effectiveness of epigenome-targeted therapies as monotherapy in hematologic malignancies, but newer studies are focused on combination therapy in many cancers. Epigenetic modifications have also been used to evaluate potential biomarkers to diagnose patients with cancer, identify patient populations likely to respond to specific anticancer therapies, and select reasonable dosages for investigational anticancer drugs, as observed with other newer targeted anticancer drugs. Although much has been learned about the relationship between the epigenome and cancer, many questions remain unanswered at this time. The next step is to continue to translate emerging epigenetic knowledge into anticancer drug development. In this review, we discuss the role of epigenetic modifications in the development of cancer and anticancer drug resistance, and we describe the progress and challenges associated with developing epigenome-targeted anticancer drugs and diagnostic tools that identify epigenetic modifications. C1 [Mummaneni, Padmaja; Shord, Stacy S.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Shord, SS (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM stacy.shord@fda.hhs.gov NR 93 TC 23 Z9 24 U1 3 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY PY 2014 VL 34 IS 5 BP 495 EP 505 DI 10.1002/phar.1408 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF7VX UT WOS:000334924200011 PM 24619798 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Interaction of potential risk factors for cancer SO SPINE JOURNAL LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, HFM 222 1401 Rockville Pike, Rockville, MD 20852 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD MAY PY 2014 VL 14 IS 5 BP 858 EP 859 DI 10.1016/j.spinee.2013.10.033 PG 3 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AF5RN UT WOS:000334770700022 PM 24216401 ER PT J AU Jarow, JP Thompson, IM Kluetz, PG Baxley, J Sridhara, R Scardino, P Carroll, P Albertsen, P Carter, HB Brawley, O Sartor, O Sandler, H Kiefert, JJ Morton, RA AF Jarow, Jonathan P. Thompson, Ian M. Kluetz, Paul G. Baxley, John Sridhara, Rajeshwari Scardino, Peter Carroll, Peter Albertsen, Peter Carter, H. Balentine Brawley, Otis Sartor, Oliver Sandler, Howard Kiefert, James J. Morton, Ronald A., Jr. TI Drug and Device Development for Localized Prostate Cancer SO UROLOGY LA English DT Article AB Of the discussion at a public workshop cosponsored by the U. S. Food and Drug Administration (FDA) and the American Urological Association reviewing potential trial designs for product and device development for the treatment of localized prostate cancer. Product development for treatment of localized prostate cancer has been stymied by the impracticality of using overall survival as an endpoint in patients with localized disease and the lack of acceptable surrogate endpoints. A workshop evaluating potential trial designs for the development of therapies for localized prostate cancer was held in San Diego, CA, in May 2013. Invited experts represented multiple stakeholders, including urology, medical oncology, radiation oncology, industry, and patient advocates. The expert panel discussed development of products for all risk strata of clinically localized prostate cancer. The panel responded to specific questions from FDA, discussing trial design for patients with low-, intermediate-, and high-risk prostate cancer, focal therapy for prostate cancer, patients who have undergone definitive radiation therapy, and adjuvant therapy for patients undergoing radiation therapy or surgery. Expert commentary provided by the panel will inform a planned FDA guidance on pathways for product and device development for treatment of localized prostate cancer and will be discussed at meetings of the FDA's Oncologic Drugs Advisory Committee. FDA intends to develop a set of principles that can be used to promote the development of new products or devices for the treatment of this disease. UROLOGY 83: 975-979, 2014. Published by Elsevier Inc. C1 [Jarow, Jonathan P.] US FDA, Off Hematol & Oncol Prod, Silver Spring, MD 20993 USA. Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. US FDA, Ctr Drug Evaluat & Res, Div Biometr 5, Off Biostat, Silver Spring, MD 20993 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, David H Koch Chair, New York, NY 10021 USA. Univ Calif San Francisco, Dept Urol, Helen Diller Comprehens Canc Ctr, San Francisco, CA USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Johns Hopkins Sch Med, Baltimore, MD USA. Emory Univ, Amer Canc Soc, Atlanta, GA 30322 USA. Tulane Univ, Sch Med, Dept Med, Tulane Canc Ctr, New Orleans, LA 70112 USA. Tulane Univ, Sch Med, Dept Urol, Tulane Canc Ctr, New Orleans, LA 70112 USA. Cedars Sinai Med Ctr, Dept Radiat Oncol, Ronald H Bloom Chair Canc Therapeut, Los Angeles, CA 90048 USA. Us TOO Int, Board Chairman Emeritus, Des Plaines, IL USA. Amer Med Syst, Minnetonka, MN USA. RP Jarow, JP (reprint author), US FDA, Off Hematol & Oncol Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Jonathan.jarow@fda.hhs.gov NR 1 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAY PY 2014 VL 83 IS 5 BP 975 EP 979 DI 10.1016/j.urology.2013.10.087 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AF5GU UT WOS:000334742800005 PM 24661332 ER PT J AU Kim, E Okada, K Beeler, JA Crim, RL Piedra, PA Gilbert, BE Gambotto, A AF Kim, Eun Okada, Kaori Beeler, Judy A. Crim, Roberta L. Piedra, Pedro A. Gilbert, Brian E. Gambotto, Andrea TI Development of an Adenovirus-Based Respiratory Syncytial Virus Vaccine: Preclinical Evaluation of Efficacy, Immunogenicity, and Enhanced Disease in a Cotton Rat Model SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODIES; FUSION GLYCOPROTEIN; INFLUENZA-VIRUS; F-PROTEIN; T-CELLS; IMMUNITY; VECTORS; INFECTION; EPITOPES; OPPORTUNITIES AB The lack of a vaccine against respiratory syncytial virus (RSV) is a challenging and serious gap in preventive medicine. Herein, we characterize the immunogenicity of an adenovirus serotype 5-based RSV vaccine encoding the fusion (F) protein (Ad5. RSV-F) and the protection provided following immunization with Ad5. RSV-F and assess its potential for producing enhanced disease in a cotton rat (CR) model. Animals were immunized intranasally (i.n.) and/or intramuscularly (i.m.) and subsequently challenged with RSV/A/Tracy (i.n.) to assess protection. Robust immune responses were seen in CRs vaccinated with Ad5. RSV-F given i.m. or i.n., and these responses correlated with reduced replication of the virus in noses and lungs after challenge. Neutralizing antibody responses following immunization with a single dose of Ad5. RSV-F at 1 x 10(11) viral particles (v.p.) elicited antibody titers 64-to 256-fold greater than those seen after natural infection. CRs boosted with Ad5. RSV-F i.n. 28 days after an i.m. dose also had significant increases in neutralizing antibody titers. Antibody affinity for different F-protein antigenic sites revealed substantial differences between antibodies elicited by Ad5. RSV-F and those seen after RSV infection; differences in antibody profiles were also seen between CRs given Ad5. RSV-F i.m. and CRs given Ad5. RSV-F i.n. Ad5. RSV-F priming did not result in enhanced disease following live-virus challenge, in contrast to the histopathology seen in CRs given the formalin-inactivated RSV/A/Burnett vaccine. C1 [Kim, Eun; Okada, Kaori; Gambotto, Andrea] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15260 USA. [Beeler, Judy A.; Crim, Roberta L.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Piedra, Pedro A.; Gilbert, Brian E.] Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Gambotto, A (reprint author), Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15260 USA. EM gambottoa@upmc.edu FU University of Pittsburgh's National Institutes of Health (NIH) Cancer Center support grant (CCSG) [P30 CA047904] FX The cotton rat studies were supported by preclinical services provided by the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID) (HHSN272201000004I). This project used the University of Pittsburgh Cancer Institute (UPCI) Vector Core Facilities, supported by the University of Pittsburgh's National Institutes of Health (NIH) Cancer Center support grant (CCSG) P30 CA047904. NR 40 TC 17 Z9 18 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2014 VL 88 IS 9 BP 5100 EP 5108 DI 10.1128/JVI.03194-13 PG 9 WC Virology SC Virology GA AE9TT UT WOS:000334353900042 PM 24574396 ER PT J AU Chow, AT Earp, JC Gupta, M Hanley, W Hu, C Wang, DD Zajic, S Zhu, M AF Chow, Andrew T. Earp, Justin C. Gupta, Manish Hanley, William Hu, Chuanpu Wang, Diane D. Zajic, Stefan Zhu, Min CA Population PK TPDI Working Grp TI Utility of Population Pharmacokinetic Modeling in the Assessment of Therapeutic Protein-Drug Interactions SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE population pharmacokinetic model; therapeutic protein; TP-drug interaction; drug-drug interaction; confirmatory PPK approach ID HUMAN MONOCLONAL-ANTIBODY; MIXED EFFECTS MODELS; RHEUMATOID-ARTHRITIS; DESIGN; IMMUNOGENICITY; METHOTREXATE; INHIBITION; INTERFERON; METABOLISM AB Assessment of pharmacokinetic (PK) based drug-drug interactions (DDI) is essential for ensuring patient safety and drug efficacy. With the substantial increase in therapeutic proteins (TP) entering the market and drug development, evaluation of TP-drug interaction (TPDI) has become increasingly important. Unlike for small molecule (e.g., chemical-based) drugs, conducting TPDI studies often presents logistical challenges, while the population PK (PPK) modeling may be a viable approach dealing with the issues. A working group was formed with members from the pharmaceutical industry and the FDA to assess the utility of PPK-based TPDI assessment including study designs, data analysis methods, and implementation strategy. This paper summarizes key issues for consideration as well as a proposed strategy with focuses on (1) PPK approach for exploratory assessment; (2) PPK approach for confirmatory assessment; (3) importance of data quality; (4) implementation strategy; and (5) potential regulatory implications. Advantages and limitations of the approach are also discussed. C1 [Chow, Andrew T.; Zhu, Min] Amgen Inc, Dept Pharmacokinet & Drug Metab, Quantitat Pharmacol, Thousand Oaks, CA 91320 USA. [Earp, Justin C.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Earp, Justin C.] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Gupta, Manish] Bristol Myers Squibb, Exploratory Clin & Translat Res, Lawrenceville, NJ USA. [Hanley, William; Zajic, Stefan] Merck & Co Inc, PK PD & Drug Metab, West Point, PA USA. [Hu, Chuanpu] Janssen Res & Dev LLC, Biol Clin Pharmacol, Spring House, PA USA. [Wang, Diane D.] Pfizer, Oncol Business Unit, Clin Pharmacol, La Jolla, CA USA. RP Zhu, M (reprint author), Amgen Inc, One Amgen Ctr Dr,28-3-B, Thousand Oaks, CA 91320 USA. EM minz@amgen.com OI Zajic, Stefan/0000-0002-9844-9951 FU Amgen; Merck FX We thank the members of the TP-DDI Steering Committee for their encouragement and support. The comments received from multiple colleagues in industry. We also acknowledge Nitin Mehrotra, Yaning Wang, and Honghui Zhou for their in-depth input to the manuscript. Amgen and Merck sponsored the simulation work for evaluation of model-based assessment of drug interaction. NR 44 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4604 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 2014 VL 54 IS 5 BP 593 EP 601 DI 10.1002/jcph.240 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AE1RZ UT WOS:000333748700013 PM 24272952 ER PT J AU McCabe, JT Moratz, C Liu, YB Burton, E Morgan, A Budinich, C Lowe, D Rosenberger, J Chen, HZ Liu, J Myers, M AF McCabe, Joseph T. Moratz, Chantal Liu, Yunbo Burton, Ellen Morgan, Amy Budinich, Craig Lowe, Dennell Rosenberger, John Chen, HuaZhen Liu, Jiong Myers, Matthew TI APPLICATION OF HIGH-INTENSITY FOCUSED ULTRASOUND TO THE STUDY OF MILD TRAUMATIC BRAIN INJURY SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE Animal models; Blast injury; Blood-brain barrier; Mouse; High-intensity focused ultrasound; Traumatic brain injury ID BLAST INJURY; IN-VIVO; MICROGLIA; BARRIER; TISSUE; MODEL; MECHANISMS; OUTCOMES; CARE; RATS AB Though intrinsically of much higher frequency than open-field blast overpressures, high-intensity focused ultrasound (HIFU) pulse trains can be frequency modulated to produce a radiation pressure having a similar form. In this study, 1.5-MHz HIFU pulse trains of 1-ms duration were applied to intact skulls of mice in vivo and resulted in blood-brain barrier disruption and immune responses (astrocyte reactivity and microglial activation). Analyses of variance indicated that 24 h after HIFU exposure, staining density for glial fibrillary acidic protein was elevated in the parietal and temporal regions of the cerebral cortex, corpus callosum and hippocampus, and staining density for the microglial marker, ionized calcium binding adaptor molecule, was elevated 2 and 24 h after exposure in the corpus callosum and hippocampus (all statistical test results, p < 0.05). HIFU shows promise for the study of some bio-effect aspects of blast-related, non-impact mild traumatic brain injuries in animals. (E-mail: Joseph.McCabe@usuhs.edu) Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology. C1 [McCabe, Joseph T.; Lowe, Dennell; Rosenberger, John; Chen, HuaZhen; Liu, Jiong] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [McCabe, Joseph T.; Moratz, Chantal; Budinich, Craig] Uniformed Serv Univ Hlth Sci, Grad Program Neurosci, Bethesda, MD 20814 USA. [McCabe, Joseph T.; Moratz, Chantal; Burton, Ellen; Morgan, Amy] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Moratz, Chantal; Burton, Ellen; Morgan, Amy] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Liu, Yunbo; Myers, Matthew] US FDA, Ctr Devices & Radiol Hlth, White Oak, MD USA. RP McCabe, JT (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM Joseph.McCabe@usuhs.edu FU U.S. Army Medical Research and Materiel Command Grant [W81 XWH-09-2-0147]; Translational Research Grant Opportunities of the Blast Lethality Injury and Research Program Grant [600-070-00000-00-106108]; Center for Neuroscience and Regenerative Medicine [G183 YL] FX This work was supported by U.S. Army Medical Research and Materiel Command Grant W81 XWH-09-2-0147 and Translational Research Grant Opportunities of the Blast Lethality Injury and Research Program Grant 600-070-00000-00-106108 to J.T.M., and Project G183 YL from The Center for Neuroscience and Regenerative Medicine to C. M.-The experiments were conducted according to the principles set forth in the Guide for Care and Use of Laboratory Animals, ILAR, National Research Council, DHEW Publication (NIH) 73-23. The opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army, Department of Defense, U.S. government or Uniformed Services University of the Health Sciences. The use of trade names does not constitute an official endorsement or approval of the use of such reagents or commercial hardware or software. This document may not be cited for purposes of advertisement. NR 57 TC 4 Z9 5 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 EI 1879-291X J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD MAY PY 2014 VL 40 IS 5 BP 965 EP 978 DI 10.1016/j.ultrasmedbio.2013.11.023 PG 14 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA AE1TR UT WOS:000333753600014 PM 24462152 ER PT J AU Liu, YB Herman, BA Soneson, JE Harris, GR AF Liu, Yunbo Herman, Bruce A. Soneson, Joshua E. Harris, Gerald R. TI THERMAL SAFETY SIMULATIONS OF TRANSIENT TEMPERATURE RISE DURING ACOUSTIC RADIATION FORCE-BASED ULTRASOUND ELASTOGRAPHY SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE Transient temperature rise; Ultrasonic heating; Radiation force elastography; Exposure regulation; Acoustic output; Acoustic radiation force impulse ID DIAGNOSTIC ULTRASOUND; SOFT-TISSUE; BONE; DERIVATION AB Ultrasound transient elastography is a new diagnostic imaging technique that uses acoustic radiation force to produce motion in solid tissue via a high-intensity, long-duration "push'' beam. In our previous work, we developed analytical models for calculating transient temperature rise, both in soft tissue and at a bone/soft tissue interface, during a single acoustic radiation force impulse (ARFI) imaging frame. The present study expands on these temperature rise calculations, providing applicable range assessment and error analysis for a single ARFI frame. Furthermore, a "virtual source'' approach is described for temperature and thermal dose calculation under multiple ARFI frames. By use of this method, the effect of inter-frame cooling duration on temperature prediction is analyzed, and a thermal buildup phenomenon is revealed. Thermal safety assessment indicates that the thermal dose values, especially at the absorptive bone/soft tissue interface, could approach recommended dose thresholds if the cooling interval of multiple-frame ARFI elastography is too short. (E-mail: yunbo.liu@fda.hhs.gov) Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology. C1 [Liu, Yunbo; Herman, Bruce A.; Soneson, Joshua E.; Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, Off Med Prod & Tobacco, Silver Spring, MD 20993 USA. RP Liu, YB (reprint author), US FDA, WO62-2126,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yunbo.liu@fda.hhs.gov NR 35 TC 5 Z9 5 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 EI 1879-291X J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD MAY PY 2014 VL 40 IS 5 BP 1001 EP 1014 DI 10.1016/j.ultrasmedbio.2013.11.015 PG 14 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA AE1TR UT WOS:000333753600017 PM 24548651 ER PT J AU Trickler, WJ Guo, XQ Cuevas, E Ali, SF Paule, MG Kanungo, J AF Trickler, William J. Guo, Xiaoqing Cuevas, Elvis Ali, Syed F. Paule, Merle G. Kanungo, Jyotshna TI Ketamine attenuates cytochrome p450 aromatase gene expression and estradiol-17 beta levels in zebrafish early life stages SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE testosterone; CYP aromatase; zebrafish; estradiol-17 beta; ketamine; gene expression ID FOLLICLE-STIMULATING-HORMONE; ENDOCRINE DISRUPTING CHEMICALS; LUTEINIZING-HORMONE; TELEOST FISH; DANIO-RERIO; ESTROGEN-RECEPTORS; CYP19 GENES; DEVELOPMENTAL EXPRESSION; PROMOTER CHARACTERISTICS; PLASMA-CONCENTRATIONS AB Ketamine, a dissociative anesthetic, is a noncompetitive antagonist of N-methyl-D-aspartate-type glutamate receptors. In rodents and non-human primates as well as in zebrafish embryos, ketamine has been shown to be neurotoxic. In cyclic female rats, ketamine has been shown to decrease serum estradiol-17 beta (E2) levels. E2 plays critical roles in neurodevelopment and neuroprotection. Cytochrome p450 (CYP) aromatase catalyzes E2 synthesis from androgens. Although ketamine down-regulates a number of CYP enzymes in rodents, its effect on the CYP aromatase (CYP19) is not known. Zebrafish have been used as a model system for examining mechanisms underlying drug effects. Here, using wild-type (WT) zebrafish (Danio rerio) embryos, we demonstrate that ketamine significantly reduced E2 levels compared with the control. However, the testosterone level was elevated in ketamine-treated embryos. These results are concordant with data from mammalian studies. Ketamine also attenuated the expression of the ovary form of CYP aromatase (cyp19a1a) at the transcriptional level but not the brain form of aromatase, cyp19a1b. Exogenous E2 potently induced the expression of cyp19a1b and vtg 1, both validated biomarkers of estrogenicity and endocrine disruption, but not cyp19a1a expression. Attenuation of activated ERK/MAPK levels, reportedly responsible for reduced human cyp19 transcription, was also observed in ketamine-treated embryos. These results suggest that reduced E2 levels in ketamine-treated embryos may have resulted from the suppression of cyp19a1a transcription. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. C1 [Trickler, William J.; Guo, Xiaoqing; Cuevas, Elvis; Ali, Syed F.; Paule, Merle G.; Kanungo, Jyotshna] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Trickler, William J.] US FDA, Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kanungo, J (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jyotshnabala.kanungo@fda.hhs.gov FU National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA) FX This work was supported by the National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA). We thank Melanie Dumas for zebrafish breeding. NR 81 TC 9 Z9 9 U1 2 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X EI 1099-1263 J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAY PY 2014 VL 34 IS 5 BP 480 EP 488 DI 10.1002/jat.2888 PG 9 WC Toxicology SC Toxicology GA AD6XN UT WOS:000333404800003 PM 23696345 ER PT J AU Hepp, NM Mindak, WR Gasper, JW Thompson, CB Barrows, JN AF Hepp, Nancy M. Mindak, William R. Gasper, John W. Thompson, Christopher B. Barrows, Julie N. TI Survey of cosmetics for arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel content SO JOURNAL OF COSMETIC SCIENCE LA English DT Article ID NEUTRON-ACTIVATION ANALYSIS; ATOMIC-ABSORPTION SPECTROSCOPY; MAKE-UP COSMETICS; HEAVY-METALS; EYE SHADOW; PRODUCTS; DERMATITIS; LIPSTICK; ELEMENTS; SAMPLES AB As part of efforts to assess amounts of inorganic element contamination in cosmetics, the U.S. Food and Drug Administration contracted a private laboratory to determine the total content of seven potentially toxic or allergenic elements in 150 cosmetic products of 12 types (eye shadows, blushes, lipsticks, three types of lotions, mascaras, foundations, body powders, compact powders, shaving creams, and face paints). Samples were analyzed for arsenic, cadmium, chromium, cobalt, lead, and nickel by inductively coupled plasma-mass spectrometry and for mercury by cold vapor atomic fluorescence spectrometry. The methods used to determine the elements were tested for validity by using standard reference materials with matrices similar to the cosmetic types. The cosmetic products were found to contain median values of 0.21 mg/kg arsenic, 3.1 mg/kg chromium, 0.91 mg/kg cobalt, 0.85 mg/kg lead, and 2.7 mg/kg nickel. The median values for cadmium and mercury were below the limits of detection of the methods. The contract requirements, testing procedures, and findings from the survey are described. C1 [Hepp, Nancy M.; Mindak, William R.; Gasper, John W.; Thompson, Christopher B.; Barrows, Julie N.] US FDA, College Pk, MD 20740 USA. RP Hepp, NM (reprint author), US FDA, College Pk, MD 20740 USA. EM Nancy.Hepp@fda.hhs.gov NR 34 TC 3 Z9 3 U1 8 U2 46 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 1525-7886 J9 J COSMET SCI JI J. Cosmet. Sci. PD MAY-JUN PY 2014 VL 65 IS 3 BP 125 EP 145 PG 21 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA CH9TB UT WOS:000354378100001 PM 25043485 ER PT J AU Choi, M Wang, J Cheng, WC Ramponi, G Albani, L Badano, A AF Choi, Mina Wang, Joel Cheng, Wei-Chung Ramponi, Giovanni Albani, Luigi Badano, Aldo TI Effect of Veiling Glare on Detectability in High-Dynamic-Range Medical Images SO JOURNAL OF DISPLAY TECHNOLOGY LA English DT Article AB We describe a methodology for predicting the detectability of subtle targets in dark regions of high-dynamic-range (HDR) images in the presence of veiling glare in the human eye. The method relies on predictions of contrast detection thresholds for the human visual system within a HDR image based on psychophysics measurements and modeling of the HDR display device characteristics. We present experimental results used to construct the model and discuss an image-dependent empirical veiling glare model and the validation of the model predictions with test patterns, natural scenes, and medical images. The model predictions are compared to a previously reported model (HDR-VDP2) for predicting HDR image quality accounting for glare effects. C1 [Choi, Mina; Wang, Joel; Cheng, Wei-Chung; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Ramponi, Giovanni] Univ Trieste, Dept Engn & Architecture, Trieste, Italy. [Albani, Luigi] BARCO FIMI, Technol Innovat Grp, Saronno, Italy. RP Choi, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU FDA; FIMI/BARCO; U.S. Food and Drug Administration Critical Path Grant FX This work was supported in part by a Cooperative Research and Development Agreement between FDA and FIMI/BARCO. The work of M. Choi was supported in part by the U.S. Food and Drug Administration Critical Path Grant. NR 27 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1551-319X EI 1558-9323 J9 J DISP TECHNOL JI J. Disp. Technol. PD MAY PY 2014 VL 10 IS 5 BP 420 EP 428 DI 10.1109/JDT.2013.2279933 PG 9 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA V44XK UT WOS:000209781500006 ER PT J AU Alam, M Costales, M Williams, K AF Alam, Mohammad Costales, Matthew Williams, Kristina TI Down-regulation of CD73 expression favors host protection during Intracellular foodborne bacterial infections SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Alam, Mohammad; Costales, Matthew; Williams, Kristina] FDA, Ctr Food Safety Nutr, Immunobiol DVA, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA IRC8P.496 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004225 ER PT J AU Berkower, I Virnik, K Hockenbury, M Rosati, M Alicea, C Valentin, A Pavlakis, G Felber, B AF Berkower, Ira Virnik, Konstantin Hockenbury, Max Rosati, Margherita Alicea, Candido Valentin, Antonio Pavlakis, George Felber, Barbara TI Live attenuated rubella vectors express HIV Env and SIV Gag antigens in the context of an acute infection and elicit high antibody titers, memory B cells, and Gag specific CD8+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Berkower, Ira; Virnik, Konstantin; Hockenbury, Max] US FDA, Ctr Biol, Bethesda, MD 20014 USA. [Rosati, Margherita; Alicea, Candido; Valentin, Antonio; Pavlakis, George; Felber, Barbara] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VIR5P.1033 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765005023 ER PT J AU Berkson, J McFarland, H Rosenberg, A AF Berkson, Julia McFarland, Hugh Rosenberg, Amy TI Rescue of vaccine T cell memory following sublethal gamma irradiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Berkson, Julia; McFarland, Hugh; Rosenberg, Amy] US FDA, Div Therapeut Prot, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA VAC3P.952 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765004185 ER PT J AU Boelte, K Sen, S Priel, DL Lau, K Cardone, M Yoshimura, T Barb, J Joehanes, R Accame, D Teer, J Singh, L Adams, L Zhang, XQ Chowdhury, S Johnson, A Green, E Mullikin, J Kolodgie, F Virmani, R O'Donnell, C Munson, P Trinchieri, G Kuhns, D Biesecker, L McVicar, D AF Boelte, Kimberly Sen, Shurjo Priel, Debra Long Lau, Karen Cardone, Marco Yoshimura, Teizo Barb, Jennifer Joehanes, Roby Accame, David Teer, Jamie Singh, Larry Adams, Lila Zhang, XiaoQing Chowdhury, Soma Johnson, Andrew Green, Eric Mullikin, James Kolodgie, Frank Virmani, Renu O'Donnell, Christopher Munson, Peter Trinchieri, Giorgio Kuhns, Douglas Biesecker, Leslie McVicar, Daniel TI TREML4 expression by myeloid cells may play a role in coronary artery disease SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Boelte, Kimberly; Cardone, Marco; Yoshimura, Teizo; Trinchieri, Giorgio; McVicar, Daniel] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Sen, Shurjo; Accame, David; Singh, Larry; Green, Eric; Mullikin, James; Biesecker, Leslie] NHGRI, NIH, Bethesda, MD 20892 USA. [Johnson, Andrew; O'Donnell, Christopher] NHLBI, NIH, Bethesda, MD 20892 USA. [Chowdhury, Soma] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Adams, Lila; Zhang, XiaoQing; Kolodgie, Frank; Virmani, Renu] CVPath Inst, Gaithersburg, MD USA. [Teer, Jamie] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Barb, Jennifer; Joehanes, Roby; Munson, Peter] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Priel, Debra Long; Lau, Karen; Kuhns, Douglas] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HUM1P.308 PG 2 WC Immunology SC Immunology GA V44RB UT WOS:000209765000235 ER PT J AU Moratz, C Peng, S AF Moratz, Chantal Peng, Suzette TI Interaction of complement-coagulation factors in ischemia/reperfusion-induced injury in autoimmune prone (B6.MRL/Ipr) mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Moratz, Chantal] Uniformed Serv Univ Hlth Sci, Med, Bethesda, MD 20814 USA. [Peng, Suzette] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA BA3P.205 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765002182 ER PT J AU Toomer, O Ferguson, M Pereira, M Do, A Bigley, E Gaines, D Williams, K AF Toomer, Ondulla Ferguson, Martine Pereira, Marion Do, Andrew Bigley, Elmer Gaines, Dennis Williams, Kristina TI Maternal and postnatal dietary probiotic supplementation enhances splenic regulatory T helper cell population and reduces ovalbumin allergen-induced hypersensitivity responses in mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Toomer, Ondulla; Ferguson, Martine; Pereira, Marion; Do, Andrew; Bigley, Elmer; Gaines, Dennis; Williams, Kristina] US FDA, CFSAN OARSA DVA Immunobiol, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2014 VL 192 SU 1 MA HYP7P.305 PG 1 WC Immunology SC Immunology GA V44RB UT WOS:000209765003158 ER PT J AU Suzuki, A Leland, P Kobayashi, H Choyke, P Jagoda, E Inoue, T Joshi, B Puri, R AF Suzuki, Akiko Leland, Pamela Kobayashi, Hisataka Choyke, Peter Jagoda, Elaine Inoue, Tomio Joshi, Bharat Puri, Raj TI Evaluation of intracranial distribution of interleukin-13 receptor directed immunotoxin after convection enhanced delivery by SPECT/CT in a human brain tumor mouse model SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI) CY JUN 07-11, 2014 CL St Louis, MO SP Soc Nucl Med & Mol Imaging C1 [Suzuki, Akiko; Leland, Pamela; Joshi, Bharat; Puri, Raj] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Kobayashi, Hisataka; Choyke, Peter; Jagoda, Elaine] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Inoue, Tomio] Yokohama City Univ, Radiol, Yokohama, Kanagawa 232, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 SU 1 MA 1027 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CR6FA UT WOS:000361438101191 ER PT J AU Nagy, A Gemmill, KB Delehanty, JB Medintz, IL Sapsford, KE AF Nagy, Amber Gemmill, Kelly Boeneman Delehanty, James B. Medintz, Igor L. Sapsford, Kim E. TI Peptide-Functionalized Quantum Dot Biosensors SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE Biosensor; bioluminescence resonance energy transfer (BRET); Forster resonance energy transfer (FRET); peptide; protease; quantum dot (QD) ID RESONANCE ENERGY-TRANSFER; PROTEASES RECENT ADVANCES; ACTIVITY-BASED PROBES; BIOLOGICAL MOLECULES; PROTEOLYTIC ACTIVITY; GOLD NANOPARTICLE; REMAINING ISSUES; ENZYME-ACTIVITY; TRANSFER RELAY; IN-VITRO AB Quantum dot (QD) nanomaterials have a number of electro-optical properties that make them ideal for biosensing applications. QDs combined with peptides have been used for both targeting and sensing applications, however this review will focus specifically on peptide-functionalized QD biosensors, whose signal transduction occurs through active modulation of the QD photo-luminescent properties. C1 [Nagy, Amber; Sapsford, Kim E.] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Gemmill, Kelly Boeneman; Delehanty, James B.; Medintz, Igor L.] US Naval Res Lab, Ctr Bio Mol Sci & Engn Code 6900, Washington, DC 20375 USA. RP Nagy, A (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM Amber.Nagy@fda.hhs.gov; Kelly.Boeneman@nrl.navy.mil; James.Delehanty@nrl.navy.mil; Igor.Medintz@nrl.navy.mil; Kim.Sapsford@fda.hhs.gov FU Oak Ridge Institute for Science and Engineering; NRI. NSI; DTRA 1ST() M1PR [13112582M] FX The work of A. Nagy was supported by a postdoctoral fellowship initiated through the Oak Ridge Institute for Science and Engineering. The work of I. I.. Medintz was supported by the NRI. NSI and DTRA 1ST() M1PR # 13112582M for financial support. The work of K. E. Sapford was supported by the Division of Biology, FDA for financial support. NR 74 TC 6 Z9 6 U1 5 U2 143 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1077-260X EI 1558-4542 J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD MAY-JUN PY 2014 VL 20 IS 3 AR 6900512 DI 10.1109/JSTQE.2013.2284427 PG 12 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 293UC UT WOS:000329998200011 ER PT J AU Turnipseed, SB Lohne, JJ Storey, JM Andersen, WC Young, SL Carr, JR Madson, MR AF Turnipseed, Sherri B. Lohne, Jack J. Storey, Joseph M. Andersen, Wendy C. Young, Susan L. Carr, Justin R. Madson, Mark R. TI Challenges in Implementing a Screening Method for Veterinary Drugs in Milk Using Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE veterinary drug residues; quadrupole time-of-flight MS; screening; milk ID ION-TRAP; ELECTROSPRAY-IONIZATION; BOVINE-MILK; MACROLIDE ANTIBIOTICS; MULTICLASS METHOD; ANIMAL ORIGIN; LC-MS; RESIDUES; CONFIRMATION; EXTRACTION AB High resolution mass spectrometry (HRMS) is a valuable tool for the analysis of chemical contaminants in food. Our laboratory has successfully developed methods to screen for veterinary drug residues using liquid chromatography quadrupole time-of-flight (Q-TOF). There have been, however, significant challenges as methods are transferred from the development stage to routine regulatory analysis. Having experimental retention time and product ion information for analytes greatly facilitates the ability to determine if residues found by the HAMS searching software are false detects. These data were collected for over 200 veterinary drug residues using LC Q-TOF MS. The screening levels of detection for over 150 veterinary drug residues in milk were determined, and over half of those tested can be detected at concentrations of 10 ng/mL or less; 72% can be found in milk when present at 100 ng/mL. Tentative identification of the product ions from these analytes is also presented. C1 [Turnipseed, Sherri B.; Lohne, Jack J.; Storey, Joseph M.; Andersen, Wendy C.; Madson, Mark R.] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. [Young, Susan L.; Carr, Justin R.; Madson, Mark R.] US FDA, Denver Sci Branch, Denver Fed Ctr, Denver, CO 80225 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Bldg 20, Denver, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 47 TC 15 Z9 15 U1 2 U2 40 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR 30 PY 2014 VL 62 IS 17 BP 3660 EP 3674 DI 10.1021/jf405321w PG 15 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA AG4DI UT WOS:000335369100003 PM 24432774 ER PT J AU Yang, HC Lin, CW Chen, CW Chen, JJ AF Yang, Hsin-Chou Lin, Chien-Wei Chen, Chia-Wei Chen, James J. TI Applying genome-wide gene-based expression quantitative trait locus mapping to study population ancestry and pharmacogenetics SO BMC GENOMICS LA English DT Article DE Gene-based approach; Expression quantitative trait locus (eQTL); Partial least squares (PLS); Ancestry-informative marker (AIM); Pharmacogenetics; Adverse drug reaction; Drug response; Drug biotransformation ID PARTIAL LEAST-SQUARES; CORONARY-HEART-DISEASE; DETERMINING CONTINENTAL ORIGIN; INTERNATIONAL HAPMAP PROJECT; INFORMATIVE MARKERS; EXPERIMENTAL CROSSES; ETHNIC-DIFFERENCES; DRUG DISPOSITION; ASSOCIATION TEST; COMPLEX TRAITS AB Background: Gene-based analysis has become popular in genomic research because of its appealing biological and statistical properties compared with those of a single-locus analysis. However, only a few, if any, studies have discussed a mapping of expression quantitative trait loci (eQTL) in a gene-based framework. Neither study has discussed ancestry-informative eQTL nor investigated their roles in pharmacogenetics by integrating single nucleotide polymorphism (SNP)-based eQTL (s-eQTL) and gene-based eQTL (g-eQTL). Results: In this g-eQTL mapping study, the transcript expression levels of genes (transcript-level genes; T-genes) were correlated with the SNPs of genes (sequence-level genes; S-genes) by using a method of gene-based partial least squares (PLS). Ancestry-informative transcripts were identified using a rank-score-based multivariate association test, and ancestry-informative eQTL were identified using Fisher's exact test. Furthermore, key ancestry-predictive eQTL were selected in a flexible discriminant analysis. We analyzed SNPs and gene expression of 210 independent people of African-, Asian- and European-descent. We identified numerous cis- and trans-acting g-eQTL and s-eQTL for each population by using PLS. We observed ancestry information enriched in eQTL. Furthermore, we identified 2 ancestry-informative eQTL associated with adverse drug reactions and/or drug response. Rs1045642, located on MDR1, is an ancestry-informative eQTL (P = 2.13E-13, using Fisher's exact test) associated with adverse drug reactions to amitriptyline and nortriptyline and drug responses to morphine. Rs20455, located in KIF6, is an ancestry-informative eQTL (P = 2.76E-23, using Fisher's exact test) associated with the response to statin drugs (e.g., pravastatin and atorvastatin). The ancestry-informative eQTL of drug biotransformation genes were also observed; cross-population cis- acting expression regulators included SPG7, TAP2, SLC7A7, and CYP4F2. Finally, we also identified key ancestry-predictive eQTL and established classification models with promising training and testing accuracies in separating samples from close populations. Conclusions: In summary, we developed a gene-based PLS procedure and a SAS macro for identifying g-eQTL and s-eQTL. We established data archives of eQTL for global populations. The program and data archives are accessible at http://www.stat.sinica.edu.tw/hsinchou/genetics/eQTL/HapMapII.htm. Finally, the results from our investigations regarding the interrelationship between eQTL, ancestry information, and pharmacodynamics provide rich resources for future eQTL studies and practical applications in population genetics and medical genetics. C1 [Yang, Hsin-Chou; Lin, Chien-Wei; Chen, Chia-Wei] Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. [Yang, Hsin-Chou] Natl Def Med Ctr, Sch Publ Hlth, Taipei, Taiwan. [Chen, James J.] US FDA, Natl Ctr Toxicol Res, Little Rock, AR USA. RP Yang, HC (reprint author), Acad Sinica, Inst Stat Sci, 128,Acad Rd,Sect 2, Taipei 11529, Taiwan. EM hsinchou@stat.sinica.edu.tw FU Career Development Award of Academia Sinica [AS-100-CDA-M03]; National Science Council of Taiwan [NSC 100-2314-B-001-005-MY3] FX This work was supported by the Career Development Award of Academia Sinica (AS-100-CDA-M03) and by research grants from the National Science Council of Taiwan (NSC 100-2314-B-001-005-MY3). Dr. Hsin-Chou Yang also thanks Oak Ridge Institute for Science and Education for supporting a short-term scholar exchange program to visit the National Center for Toxicological Research. The views presented in this paper are those of the authors and do not necessarily represent those of the U.S. Food and Drug Administration. We also thank two anonymous reviewers for their instructive comments that helped in preparing our revision. NR 118 TC 3 Z9 3 U1 1 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 29 PY 2014 VL 15 AR 319 DI 10.1186/1471-2164-15-319 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AG7MK UT WOS:000335601900001 PM 24779372 ER PT J AU Bellayr, IH Catalano, JG Lababidi, S Yang, AX Lo Surdo, JL Bauer, SR Puri, RK AF Bellayr, Ian H. Catalano, Jennifer G. Lababidi, Samir Yang, Amy X. Lo Surdo, Jessica L. Bauer, Steven R. Puri, Raj K. TI Gene markers of cellular aging in human multipotent stromal cells in culture SO STEM CELL RESEARCH & THERAPY LA English DT Article ID MESENCHYMAL STEM-CELLS; HUMAN BONE-MARROW; UMBILICAL-CORD BLOOD; IN-VITRO; OSTEOGENIC DIFFERENTIATION; DEVELOPMENTAL REGULATION; REPLICATIVE SENESCENCE; TRANSCRIPTION FACTOR; NERVOUS-SYSTEM; ADIPOSE-TISSUE AB Introduction: Human multipotent stromal cells (MSCs) isolated from bone marrow or other tissue sources have great potential to treat a wide range of injuries and disorders in the field of regenerative medicine and tissue engineering. In particular, MSCs have inherent characteristics to suppress the immune system and are being studied in clinical studies to prevent graft-versus-host disease. MSCs can be expanded in vitro and have potential for differentiation into multiple cell lineages. However, the impact of cell passaging on gene expression and function of the cells has not been determined. Methods: Commercially available human MSCs derived from bone marrow from six different donors, grown under identical culture conditions and harvested at cell passages 3, 5, and 7, were analyzed with gene-expression profiling by using microarray technology. Results: The phenotype of these cells did not change as reported previously; however, a statistical analysis revealed a set of 78 significant genes that were distinguishable in expression between passages 3 and 7. None of these significant genes corresponded to the markers established by the International Society for Cellular Therapy (ISCT) for MSC identification. When the significant gene lists were analyzed through pathway analysis, these genes were involved in the top-scoring networks of cellular growth and proliferation and cellular development. A meta-analysis of the literature for significant genes revealed that the MSCs seem to be undergoing differentiation into a senescent cell type when cultured extensively. Consistent with the differences in gene expression at passage 3 and 7, MSCs exhibited a significantly greater potential for cell division at passage 3 in comparison to passage 7. Conclusions: Our results identified specific gene markers that distinguish aging MSCs grown in cell culture. Confirmatory studies are needed to correlate these molecular markers with biologic attributes that may facilitate the development of assays to test the quality of MSCs before clinical use. C1 [Bellayr, Ian H.; Catalano, Jennifer G.; Yang, Amy X.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol & Evaluat Res, Bethesda, MD 20014 USA. [Lababidi, Samir] US FDA, Off Biostat & Epidemiol, Ctr Biol & Evaluat Res, Rockville, MD 20857 USA. [Lo Surdo, Jessica L.; Bauer, Steven R.] US FDA, Cellular & Tissue Therapies Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol & Evaluat Res, Bethesda, MD 20014 USA. EM raj.puri@fda.hhs.gov FU U.S. Department of Energy; U.S. Food and Drug Administration; Medical Countermeasures Initiative; FDA Modernizing Science Initiative FX This project was supported in part by an appointment of Ian Bellayr to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. This project was also supported by the Medical Countermeasures Initiative and the FDA Modernizing Science Initiative. We thank the members of the FDA Modernizing Science Consortium for their discussion of the presented work, in addition to Drs. Brenton McCright and Shyh-Ching Lo for reviewing the manuscript. NR 89 TC 17 Z9 17 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-6512 J9 STEM CELL RES THER JI Stem Cell Res. Ther. PD APR 28 PY 2014 VL 5 AR 59 DI 10.1186/scrt448 PG 22 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AH1GO UT WOS:000335868000001 PM 24780490 ER PT J AU Mathur, AK Schaubel, DE Zhang, H Guidinger, MK Merion, RM AF Mathur, Amit K. Schaubel, Douglas E. Zhang, Hui Guidinger, Mary K. Merion, Robert M. TI Disparities in Liver Transplantation: The Association Between Donor Quality and Recipient Race/Ethnicity and Sex SO TRANSPLANTATION LA English DT Article DE Racial and ethnic disparities; Liver transplantation; Liver graft survival; Donor risk; Clinical outcomes ID SURVIVAL BENEFIT; GRAFT-SURVIVAL; UNITED-STATES; OUTCOMES; ACCESS; RACE; ADULT AB Background. We aimed to examine the association between recipient race/ethnicity and sex, donor liver quality, and liver transplant graft survival. Methods. Adult nonYstatus 1 liver recipients transplanted between March 1, 2002, and December 31, 2008, were identified using Scientific Registry of Transplant Recipients data. The factors of interest were recipient race/ethnicity and sex. Donor risk index (DRI) was used as a donor quality measure. Logistic regression was used to assess the association between race/ethnicity and sex in relation to the transplantation of low-quality (high DRI) or high-quality (low DRI) livers. Cox regression was used to assess the association between race/ethnicity and sex and liver graft failure risk, accounting for DRI. Results. Hispanics were 21% more likely to receive low-quality grafts compared to whites (odds ratio [OR]=1.21, P=0.002). Women had greater odds of receiving a low-quality graft compared to men (OR=1.24, PG0.0001). Despite adjustment for donor quality, African American recipients still had higher graft failure rates compared to whites (hazard ratio [HR]=1.28, PG0.001). Hispanics (HR=0.89, P=0.023) had significantly lower graft failure rates compared to whites despite higher odds of receiving a higher DRI graft. Using an interaction model of DRI and race/ethnicity, we found that the impact of DRI on graft failure rates was significantly reduced for African Americans compared to whites (P=0.02). Conclusions. This study shows that while liver graft quality differed significantly by recipient race/ethnicity and sex, donor selection practices do not seem to be the dominant factor responsible for worse liver transplant outcomes for minority recipients. C1 [Mathur, Amit K.; Merion, Robert M.] Univ Michigan, Dept Surg, Sect Transplantat, Ann Arbor, MI 48109 USA. [Schaubel, Douglas E.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Zhang, Hui] US FDA, Silver Spring, MD USA. [Guidinger, Mary K.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Merion, Robert M.] Arbor Res Collaborat Hlth, Ann Arbor, MI USA. RP Mathur, AK (reprint author), 2922 Taubman Ctr, 1500 E Med Ctr Dr,SPC 5300, Ann Arbor, MI 48109 USA. EM amitmath@med.umich.edu FU University of Michigan Center for Integrated Approaches in Health Disparities; National Institutes of Health [5R01DK070869, T32 CA009672-18, L60 MD002968-01] FX Funding support was obtained from the University of Michigan Center for Integrated Approaches in Health Disparities (A. K. M., H.Z.) and in part by National Institutes of Health grants 5R01DK070869 (D. E. S., H.Z.), T32 CA009672-18 (A. K. M.), and L60 MD002968-01 (A.K.M.). NR 20 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2014 VL 97 IS 8 BP 862 EP 869 DI 10.1097/01.tp.0000438634.44461.67 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AH0XS UT WOS:000335844700010 PM 24345895 ER PT J AU Hick, JL Hanfling, D Courtney, B Lurie, N AF Hick, John L. Hanfling, Dan Courtney, Brooke Lurie, Nicole TI Rationing Salt Water - Disaster Planning and Daily Care Delivery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Hick, John L.] Univ Minnesota, Dept Emergency Med, Minneapolis, MN 55455 USA. [Hick, John L.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Hanfling, Dan] George Washington Univ, Dept Emergency Med, Washington, DC USA. [Lurie, Nicole] Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Hanfling, Dan] Inova Hlth Syst, Falls Church, VA USA. [Courtney, Brooke] US FDA, Off Counterterrorism & Emerging Threats, Silver Spring, MD USA. RP Hick, JL (reprint author), Univ Minnesota, Dept Emergency Med, Minneapolis, MN 55455 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 24 PY 2014 VL 370 IS 17 BP 1573 EP 1576 DI 10.1056/NEJMp1401833 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AH4TG UT WOS:000336120500002 PM 24645847 ER PT J AU Sadat, MA Moir, S Chun, TW Lusso, P Kaplan, G Wolfe, L Memoli, MJ He, M Vega, H Kim, LJY Huang, Y Hussein, N Nievas, E Mitchell, R Garofalo, M Louie, A Ireland, DC Grunes, C Cimbro, R Patel, V Holzapfel, G Salahuddin, D Bristol, T Adams, D Marciano, BE Hegde, M Li, YX Calvo, KR Stoddard, J Justement, JS Jacques, J Priel, DAL Murray, D Sun, P Kuhns, DB Boerkoel, CF Chiorini, JA Di Pasquale, G Verthelyi, D Rosenzweig, SD AF Sadat, Mohammed A. Moir, Susan Chun, Tae-Wook Lusso, Paolo Kaplan, Gerardo Wolfe, Lynne Memoli, Matthew J. He, Miao Vega, Hugo Kim, Leo J. Y. Huang, Yan Hussein, Nadia Nievas, Elma Mitchell, Raquel Garofalo, Mary Louie, Aaron Ireland, Derek C. Grunes, Claire Cimbro, Raffaello Patel, Vyomesh Holzapfel, Genevieve Salahuddin, Daniel Bristol, Tyler Adams, David Marciano, Beatriz E. Hegde, Madhuri Li, Yuxing Calvo, Katherine R. Stoddard, Jennifer Justement, J. Shawn Jacques, Jerome Priel, Debra A. Long Murray, Danielle Sun, Peter Kuhns, Douglas B. Boerkoel, Cornelius F. Chiorini, John A. Di Pasquale, Giovanni Verthelyi, Daniela Rosenzweig, Sergio D. TI Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTIRETROVIRAL THERAPY; OTITIS-MEDIA; HIV; BIOSYNTHESIS; RESERVOIR; CHILDREN; EFFICACY; ENTRY; CD4 AB Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections. C1 [Sadat, Mohammed A.; Hussein, Nadia; Nievas, Elma; Mitchell, Raquel; Garofalo, Mary; Rosenzweig, Sergio D.] NIAID, Infect Dis Susceptibil Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Moir, Susan; Chun, Tae-Wook; Lusso, Paolo; Kim, Leo J. Y.; Louie, Aaron; Cimbro, Raffaello; Justement, J. Shawn; Murray, Danielle] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Memoli, Matthew J.; Bristol, Tyler] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Marciano, Beatriz E.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Holzapfel, Genevieve; Salahuddin, Daniel; Sun, Peter] NIAID, Lab Immunogenet, NIH, Bethesda, MD 20892 USA. [Rosenzweig, Sergio D.] NIAID, Primary Immunodeficiency Clin, NIH, Bethesda, MD 20892 USA. [Wolfe, Lynne; Vega, Hugo; Huang, Yan; Adams, David; Boerkoel, Cornelius F.] Natl Human Res Genome Inst, Undiagnosed Dis Program, NIH, Bethesda, MD USA. [Calvo, Katherine R.; Stoddard, Jennifer] Natl Inst Dent & Craniofacial Res, Dept Lab Med, Clin Ctr, NIH, Bethesda, MD USA. [Patel, Vyomesh] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Chiorini, John A.; Di Pasquale, Giovanni] Natl Inst Dent & Craniofacial Res, Adeno Associated Virus Biol Sect, NIH, Bethesda, MD USA. [Kaplan, Gerardo; Jacques, Jerome] Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Ireland, Derek C.; Grunes, Claire; Verthelyi, Daniela] Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Priel, Debra A. Long; Kuhns, Douglas B.] US FDA, Clin Serv Program, Silver Spring, MD USA. [Priel, Debra A. Long; Kuhns, Douglas B.] Frederick Natl Lab Canc Res, SAIC Frederick, Frederick, MD USA. [He, Miao; Hegde, Madhuri] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Li, Yuxing] Ctr Neutralizing Antibodies TSRI, IAVI Int AIDS Vaccine Initiat, La Jolla, CA USA. [Li, Yuxing] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA USA. RP Rosenzweig, SD (reprint author), CC, Serv Immunol, DLM, 10 Ctr Dr,Bldg 10 2C410F, Bethesda, MD 20892 USA. EM srosenzweig@cc.nih.gov OI Calvo, Katherine/0000-0002-0771-4191; Cimbro, Raffaello/0000-0002-6251-5160 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute [HHSN261200800001E] FX Supported by the Intramural Research Program of the National Institutes of Health and by a grant from the National Cancer Institute (HHSN261200800001E). NR 22 TC 21 Z9 21 U1 1 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 24 PY 2014 VL 370 IS 17 BP 1615 EP 1625 DI 10.1056/NEJMoa1302846 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AH4TG UT WOS:000336120500008 PM 24716661 ER PT J AU Cai, Y Geutjes, EJ de Lint, K Roepman, P Bruurs, L Yu, LR Wang, W van Blijswijk, J Mohammad, H de Rink, I Bernards, R Baylin, SB AF Cai, Y. Geutjes, E-J de Lint, K. Roepman, P. Bruurs, L. Yu, L-R Wang, W. van Blijswijk, J. Mohammad, H. de Rink, I. Bernards, R. Baylin, S. B. TI The NuRD complex cooperates with DNMTs to maintain silencing of key colorectal tumor suppressor genes SO ONCOGENE LA English DT Article DE NuRD; DNMTs; tumor suppressor genes; silencing; colon cancer; WNT signaling ID HISTONE DEACETYLASE INHIBITION; CHROMATIN-REMODELING COMPLEX; DNA METHYLATION; FACTOR CHD4; CANCER; METHYLTRANSFERASE; HYPERMETHYLATION; DEMETHYLATION; EXPRESSION; DAMAGE AB Many tumor suppressor genes (TSGs) are silenced through synergistic layers of epigenetic regulation including abnormal DNA hypermethylation of promoter CpG islands, repressive chromatin modifications and enhanced nucleosome deposition over transcription start sites. The protein complexes responsible for silencing of many of such TSGs remain to be identified. Our previous work demonstrated that multiple silenced TSGs in colorectal cancer cells can be partially reactivated by DNA demethylation in cells disrupted for the DNA methyltransferases 1 and 3B (DNMT1 and 3B) or by DNMTi inhibitors (DNMTi). Herein, we used proteomic and functional genetic approaches to identify additional proteins that cooperate with DNMTs in silencing these key silenced TSGs in colon cancer cells. We discovered that DNMTs and the core components of the NuRD (Mi-2/nucleosome remodeling and deacetylase) nucleosome remodeling complex, chromo domain helicase DNA-binding protein 4 (CHD4) and histone deacetylase 1 (HDAC1) occupy the promoters of several of these hypermethylated TSGs and physically and functionally interact to maintain their silencing. Consistent with this, we find an inverse relationship between expression of HDAC1 and 2 and these TSGs in a large panel of primary colorectal tumors. We demonstrate that DNMTs and NuRD cooperate to maintain the silencing of several negative regulators of the WNT and other signaling pathways. We find that depletion of CHD4 is synergistic with DNMT inhibition in reducing the viability of colon cancer cells in correlation with reactivation of TSGs, suggesting that their combined inhibition may be beneficial for the treatment of colon cancer. Since CHD4 has ATPase activity, our data identify CHD4 as a potentially novel drug target in cancer. C1 [Cai, Y.; Wang, W.; Mohammad, H.; Baylin, S. B.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21287 USA. [Cai, Y.; Wang, W.; Mohammad, H.; Baylin, S. B.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Geutjes, E-J; de Lint, K.; Bruurs, L.; van Blijswijk, J.; Bernards, R.] Netherlands Canc Inst, Div Mol Carcinogenesis, Ctr Biomed Genet, NL-1066 CX Amsterdam, North Holland, Netherlands. [Geutjes, E-J; de Lint, K.; Bruurs, L.; van Blijswijk, J.; Bernards, R.] Netherlands Canc Inst, Canc Genom Ctr, NL-1066 CX Amsterdam, North Holland, Netherlands. [Roepman, P.] Agendia NV, Dept Res & Dev, Amsterdam, Netherlands. [Yu, L-R] US FDA, Div Syst Biol, Ctr Excellence Prote, Natl Ctr Toxicol Res, Jefferson, AR USA. [de Rink, I.] Netherlands Canc Inst, Cent Microarray & Deep Sequencing Core Facil, NL-1066 CX Amsterdam, North Holland, Netherlands. RP Bernards, R (reprint author), Netherlands Canc Inst, Div Mol Carcinogenesis, 121 Plesmanlaan, NL-1066 CX Amsterdam, North Holland, Netherlands. EM r.bernards@nki.nl; sbaylin@jhmi.edu OI Bernards, Rene/0000-0001-8677-3423 FU Netherlands Organization for Scientific Research (NWO); National Institute of Environmental Health Sciences (NIEHS) [ES011858]; National Cancer Institute (NCI) [CA043318] FX We thank JH Dannenberg for the gift of Hdac1 plasmids. We thank JH Dannenberg, P Kumar and members of the Bernards, Baylin laboratory for discussions and Kathy Bender and H. Liu for manuscript preparation. This work was supported by a grant from the Netherlands Organization for Scientific Research (NWO) to RB, and by grants ES011858 National Institute of Environmental Health Sciences (NIEHS) CA043318 National Cancer Institute (NCI) to SB. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 51 TC 24 Z9 25 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD APR 24 PY 2014 VL 33 IS 17 BP 2157 EP 2168 DI 10.1038/onc.2013.178 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AF8WJ UT WOS:000334996000002 PM 23708667 ER PT J AU Restaino, SM Abliz, E Wachrathit, K Krauthamer, V Shah, SB AF Restaino, Stephen M. Abliz, Erkinay Wachrathit, Kelliann Krauthamer, Victor Shah, Sameer B. TI Biomechanical and functional variation in rat sciatic nerve following cuff electrode implantation SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Article DE Peripheral nerve; Cuff; Electrode; Electrophysiology; Biomechanics; Electromyography; EMG ID PERIPHERAL-NERVE; VAGUS NERVE; LONG-TERM; CONDUCTION-VELOCITY; LARYNGEAL FUNCTION; VISUAL PROSTHESIS; STIMULATION VNS; TNF-ALPHA; STRAIN; REGENERATION AB Background: Nerve cuff electrodes are commonly and successfully used for stimulating peripheral nerves. On the other hand, they occasionally induce functional and morphological changes following chronic implantation, for reasons not always clear. We hypothesize that restriction of nerve mobility due to cuff implantation may alter nerve conduction. Methods: We quantified acute changes in nerve-muscle electrophysiology, using electromyography, and nerve kinematics in anesthetized Sprague Dawley rat sciatic nerves during controlled hindlimb joint movement. We compared electrophysiological and biomechanical response in uncuffed nerves and those secured within a cuff electrode using analysis of variance (ANOVA) and regression analysis. Results: Tethering resulting from cuff implantation resulted in altered nerve strain and a complex biomechanical environment during joint movement. Coincident with biomechanical changes, electromyography revealed significantly increased variability in the response of conduction latency and amplitude in cuffed, but not free, nerves following joint movement. Conclusion: Our findings emphasize the importance of the mechanical interface between peripheral nerves and their devices on neurophysiological performance. This work has implications for nerve device design, implantation, and prediction of long-term efficacy. C1 [Restaino, Stephen M.; Abliz, Erkinay; Wachrathit, Kelliann; Shah, Sameer B.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Restaino, Stephen M.; Abliz, Erkinay; Wachrathit, Kelliann; Krauthamer, Victor] US FDA, Div Phys, OSEL, CDRH, Silver Spring, MD USA. [Shah, Sameer B.] Univ Calif San Diego, Dept Orthopaed Surg, La Jolla, CA 92093 USA. [Shah, Sameer B.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Shah, SB (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. EM sbshah@ucsd.edu FU National Science Foundation [CBET1042522]; U.S. Army Medical Research and Materiel Command [W81XWH1010773] FX This research was supported by grant CBET1042522 from the National Science Foundation and grant W81XWH1010773 from the U.S. Army Medical Research and Materiel Command. We also acknowledge helpful discussions with members of the Neuromuscular Bioengineering Laboratory, Dr. Cristin Welle and other members of the USFDA Biophysics Laboratory. NR 74 TC 6 Z9 6 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD APR 23 PY 2014 VL 11 AR 73 DI 10.1186/1743-0003-11-73 PG 10 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA AK6WS UT WOS:000338568600001 PM 24758405 ER PT J AU Khurana, S Coyle, EM Dimitrova, M Castellino, F Nicholson, K Del Giudice, G Golding, H AF Khurana, Surender Coyle, Elizabeth M. Dimitrova, Milena Castellino, Flora Nicholson, Karl Del Giudice, Giuseppe Golding, Hana TI Heterologous Prime-Boost Vaccination with MF59-Adjuvanted H5 Vaccines Promotes Antibody Affinity Maturation towards the Hemagglutinin HA1 Domain and Broad H5N1 Cross-Clade Neutralization SO PLOS ONE LA English DT Article ID MEMORY B-CELLS; SECRETING CELLS; VIRUS-INFECTION; WILD-TYPE; INFLUENZA; PERSISTENCE; RESPONSES; IMMUNITY; EPITOPE; ADULTS AB In an open label clinical study (2007), MF59-adjuvanted hemagglutinin (HA) vaccine from H5N1-A/Vietnam/1194/2004 (clade1) was administered to subjects previously vaccinated (primed) with clade 0 H5N3 (A/duck/Singapore/97) vaccine at least 6 years earlier (in 1999 or 2001). The primed individuals responded rapidly and generated high neutralizing antibody titers against the H5N1-Vietnam strain within 7 days of a single booster vaccination. Furthermore, significant cross-neutralization titers were measured against H5N1 clade 0, 1, and 2 viruses. In the current study, the impact of MF59 adjuvant during heterologous priming on the quality of humoral polyclonal immune response in different vaccine arms were further evaluated using real time kinetics assay by surface plasmon resonance (SPR). Total anti- H5N1 HA1 polyclonal sera antibody binding from the heterologous prime-boost groups after a single MF59-H5N1 boost was significantly higher compared with sera from unprimed individuals that received two MF59-H5N1 vaccinations. The antigen-antibody complex dissociation rates (surrogate for antibody affinity) of the polyclonal sera against HA1 of H5N1-A/Vietnam/1194/2004 from the MF59-H5N3 primed groups were significantly higher compared to sera from unadjuvanted primed groups or unprimed individuals that received two MF59-H5N1 vaccines. Furthermore, strong inverse correlations were observed between the antibody dissociation off-rates of the immune sera against HA1 (but not HA2) and the virus neutralization titers against H5 vaccine strains and heterologous H5N1 strains. These findings supports the use of oil-in-water-adjuvanted pandemic influenza vaccines to elicit long term memory B cells with high affinity BCR capable of responding to potential variant pandemic viruses likely to emerge and adapt to human transmissions. C1 [Khurana, Surender; Coyle, Elizabeth M.; Dimitrova, Milena; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. [Castellino, Flora; Del Giudice, Giuseppe] Novartis Vaccines & Diagnost Srl, Siena, Italy. [Nicholson, Karl] Univ Leicester, Dept Infect Inflammat & Immun, Leicester, Leics, England. RP Khurana, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. EM surender.khurana@fda.hhs.gov; hana.golding@fda.hhs.gov FU BARDA/HHS FX This study was partially supported by a BARDA/HHS funding. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 8 Z9 8 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 22 PY 2014 VL 9 IS 4 AR e95496 DI 10.1371/journal.pone.0095496 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG2IS UT WOS:000335240300047 PM 24755693 ER PT J AU Yol, AM AF Yol, Aleer M. TI NOT LOST, BUT FOUND SO CHEMICAL & ENGINEERING NEWS LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Yol, AM (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2347 EI 1520-605X J9 CHEM ENG NEWS JI Chem. Eng. News PD APR 21 PY 2014 VL 92 IS 16 BP 42 EP 42 PG 1 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA AR1MR UT WOS:000343349800060 ER PT J AU Ellis, LM Bernstein, DS Voest, EE Berlin, JD Sargent, D Cortazar, P Garrett-Mayer, E Herbst, RS Lilenbaum, RC Sima, C Venook, AP Gonen, M Schilsky, RL Meropol, NJ Schnipper, LE AF Ellis, Lee M. Bernstein, David S. Voest, Emile E. Berlin, Jordan D. Sargent, Daniel Cortazar, Patricia Garrett-Mayer, Elizabeth Herbst, Roy S. Lilenbaum, Rogerio C. Sima, Camelia Venook, Alan P. Gonen, Mithat Schilsky, Richard L. Meropol, Neal J. Schnipper, Lowell E. TI American Society of Clinical Oncology Perspective: Raising the Bar for Clinical Trials by Defining Clinically Meaningful Outcomes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTATIC BREAST-CANCER; CELL LUNG-CANCER; PANCREATIC-CANCER; HEDGEHOG PATHWAY; APPROVAL; INHIBITION; SURVIVAL; CHEMOTHERAPY; TRASTUZUMAB; GEMCITABINE C1 [Ellis, Lee M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77230 USA. [Bernstein, David S.; Schilsky, Richard L.] Amer Soc Clin Oncol, Alexandria, VA USA. [Voest, Emile E.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Berlin, Jordan D.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Sargent, Daniel] Mayo Clin, Rochester, MN USA. [Cortazar, Patricia] US FDA, Silver Spring, MD USA. [Garrett-Mayer, Elizabeth] Med Univ S Carolina, Charleston, SC 29425 USA. [Herbst, Roy S.; Lilenbaum, Rogerio C.] Yale Canc Ctr, New Haven, CT USA. [Sima, Camelia; Gonen, Mithat] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Venook, Alan P.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Meropol, Neal J.] Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Schnipper, Lowell E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Ellis, LM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, POB 301402, Houston, TX 77230 USA. EM lellis@mdanderson.org NR 27 TC 111 Z9 114 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2014 VL 32 IS 12 BP 1277 EP + DI 10.1200/JCO.2013.53.8009 PG 7 WC Oncology SC Oncology GA AG0XL UT WOS:000335139000019 PM 24638016 ER PT J AU Crim, SM Iwamoto, M Huang, JY Griffin, PM Gilliss, D Cronquist, AB Cartter, M Tobin-D'Angelo, M Blythe, D Smith, K Lathrop, S Zansky, S Cieslak, PR Dunn, J Holt, KG Lance, S Tauxe, R Henao, OL AF Crim, Stacy M. Iwamoto, Martha Huang, Jennifer Y. Griffin, Patricia M. Gilliss, Debra Cronquist, Alicia B. Cartter, Matthew Tobin-D'Angelo, Melissa Blythe, David Smith, Kirk Lathrop, Sarah Zansky, Shelley Cieslak, Paul R. Dunn, John Holt, Kristin G. Lance, Susan Tauxe, Robert Henao, Olga L. TI Incidence and Trends of Infection with Pathogens Transmitted Commonly Through Food - Foodborne Diseases Active Surveillance Network, 10 US Sites, 2006-2013 SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article ID UNITED-STATES C1 [Crim, Stacy M.; Iwamoto, Martha; Huang, Jennifer Y.; Griffin, Patricia M.; Tauxe, Robert; Henao, Olga L.] CDC, Div Foodborne Waterborne & Environm Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Gilliss, Debra] California Dept Publ Hlth, Sacramento, CA USA. [Cronquist, Alicia B.] Colorado Dept Publ Hlth & Environm, Arvada, CO USA. [Tobin-D'Angelo, Melissa] Georgia Dept Publ Hlth, Atlanta, GA USA. [Blythe, David] Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. [Smith, Kirk] Minnesota Dept Hlth, Minneapolis, MN 55414 USA. [Lathrop, Sarah] Univ New Mexico, Albuquerque, NM 87131 USA. [Zansky, Shelley] New York State Dept Hlth, Albany, NY 12237 USA. [Cieslak, Paul R.] Oregon Hlth Author, Salem, OR USA. [Dunn, John] Tennessee Dept Hlth, Memphis, TN USA. [Holt, Kristin G.] US Food Safety & Inspect Serv, USDA, Washington, DC 20250 USA. [Lance, Susan] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Henao, OL (reprint author), CDC, Div Foodborne Waterborne & Environm Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. EM ohenao@cdc.gov NR 10 TC 79 Z9 80 U1 3 U2 26 PU CENTER DISEASE CONTROL & PREVENTION PI ATLANTA PA MAILSTOP E-90, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD APR 18 PY 2014 VL 63 IS 15 BP 328 EP 332 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AF1VY UT WOS:000334503200003 PM 24739341 ER PT J AU Nelson, C Hojvat, S Johnson, B Petersen, J Schriefer, M Ben Beard, C Petersen, L Mead, P AF Nelson, Christina Hojvat, Sally Johnson, Barbara Petersen, Jeannine Schriefer, Marty Ben Beard, C. Petersen, Lyle Mead, Paul TI Concerns Regarding a New Culture Method for Borrelia burgdorferi Not Approved for the Diagnosis of Lyme Disease SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article C1 [Nelson, Christina; Johnson, Barbara; Petersen, Jeannine; Schriefer, Marty; Ben Beard, C.; Petersen, Lyle; Mead, Paul] CDC, Div Vector Borne Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Hojvat, Sally] US FDA, Div Microbiol Devices, Off In Vitro Diagnost & Radiol Hlth, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Nelson, C (reprint author), CDC, Div Vector Borne Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. EM wje1@cdc.gov NR 6 TC 11 Z9 11 U1 0 U2 4 PU CENTER DISEASE CONTROL & PREVENTION PI ATLANTA PA MAILSTOP E-90, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD APR 18 PY 2014 VL 63 IS 15 BP 333 EP 333 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AF1VY UT WOS:000334503200004 PM 24739342 ER PT J AU Pettengill, JB Timme, RE Barrangou, R Toro, M Allard, MW Strain, E Musser, SM Brown, EW AF Pettengill, James B. Timme, Ruth E. Barrangou, Rodolphe Toro, Magaly Allard, Marc W. Strain, Errol Musser, Steven M. Brown, Eric W. TI The evolutionary history and diagnostic utility of the CRISPR-Cas system within Salmonella enterica ssp enterica SO PEERJ LA English DT Article DE Salmonella; Horizontal gene transfer; Evolution; CRISPR; Outbreak; Phylogeny; Whole genome sequencing; Typing ID FIELD GEL-ELECTROPHORESIS; MULTILOCUS GENOTYPE DATA; ACQUIRED-RESISTANCE; ADAPTIVE IMMUNITY; ESCHERICHIA-COLI; DNA ELEMENTS; PROKARYOTES; BACTERIA; ARCHAEA; INTERFERENCE AB Evolutionary studies of clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (cas) genes can provide insights into host-pathogen co-evolutionary dynamics and the frequency at which different genomic events (e.g., horizontal vs. vertical transmission) occur. Within this study, we used whole genome sequence (WGS) data to determine the evolutionary history and genetic diversity of CRISPR loci and cas genes among a diverse set of 427 Salmonella enterica ssp. enterica isolates representing 64 different serovars. We also evaluated the performance of CRISPR loci for typing when compared to whole genome and multilocus sequence typing (MLST) approaches. We found that there was high diversity in array length within both CRISPR1 (median = 22; min = 3; max = 79) and CRISPR2 (median = 27; min = 2; max = 221). There was also much diversity within serovars (e.g., arrays differed by as many as 50 repeat-spacer units among Salmonella ser. Senftenberg isolates). Interestingly, we found that there are two general cas gene profiles that do not track phylogenetic relationships, which suggests that non-vertical transmission events have occurred frequently throughout the evolutionary history of the sampled isolates. There is also considerable variation among the ranges of pairwise distances estimated within each cas gene, which may be indicative of the strength of natural selection acting on those genes. We developed a novel clustering approach based on CRISPR spacer content, but found that typing based on CRISPRs was less accurate than the MLST-based alternative; typing based on WGS data was the most accurate. Notwithstanding cost and accessibility, we anticipate that draft genome sequencing, due to its greater discriminatory power, will eventually become routine for traceback investigations. C1 [Pettengill, James B.; Timme, Ruth E.; Allard, Marc W.; Strain, Errol; Musser, Steven M.; Brown, Eric W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Barrangou, Rodolphe] N Carolina State Univ, Dept Food Bioproc & Nutr Sci, Raleigh, NC 27695 USA. [Toro, Magaly] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Pettengill, JB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM james.pettengill@fda.hhs.gov RI Barrangou, Rodolphe/I-2878-2014; Toro, Magaly/F-6525-2011 OI Barrangou, Rodolphe/0000-0002-0648-3504; Toro, Magaly/0000-0002-6280-2215 FU Center for Food Safety and Applied Nutrition at the US Food and Drug Administration FX This work was supported by the Center for Food Safety and Applied Nutrition at the US Food and Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 74 TC 8 Z9 8 U1 1 U2 15 PU PEERJ INC PI LONDON PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND SN 2167-8359 J9 PEERJ JI PeerJ PD APR 17 PY 2014 VL 2 AR e340 DI 10.7717/peerj.340 PG 25 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY4TI UT WOS:000347570500001 PM 24765574 ER PT J AU Khurana, S King, LR Manischewitz, J Coyle, EM Golding, H AF Khurana, Surender King, Lisa R. Manischewitz, Jody Coyle, Elizabeth M. Golding, Hana TI Novel antibody-independent receptor-binding SPR-based assay for rapid measurement of influenza vaccine potency SO VACCINE LA English DT Article DE Hemagglutinin; Influenza; Vaccine; SRID; Potency; SPR ID SINGLE-RADIAL-IMMUNODIFFUSION; MASS-TRANSPORT LIMITATION; H5N1 VACCINE; BIOSENSOR TECHNOLOGY; VIRUS; HEMAGGLUTININ; IMMUNOGENICITY; FERRETS; SAFETY; QUANTIFICATION AB A WHO workshop organized following the 2009 H1N1 pandemic recommended development of alternative influenza vaccine potency assays as high priority that could expedite the release of vaccine lots in the face of future influenza pandemics. We have developed an antibody independent, simple, high throughput receptor-binding SPR-based potency assay, which does not require any reference antisera and could be used for rapid HA quantitation and vaccine release in pandemic scenarios. The assay utilizes synthetic glycans with sialic acid (SA) of either alpha-2,6 or alpha-2,3 linkage to galactose. Only functionally active forms of HA (trimers and oligomers) recognize the SA-glycans and are quantified in this receptor-binding SPR assay. The SA-glycan SPR assay demonstrated broad dynamic range for quantitation of HA content in influenza vaccines from different manufacturers for both seasonal (A/H1N1, A/H3N2, B lineages) and pandemic influenza (A/H5N1, A/H7N9) strains with high reproducibility and low variability across multiple assays. In addition, the SA-glycan SPR assay is indicative of active HA stability, and can accurately quantify HA content in alum and oil-in-water adjuvanted influenza vaccines. Importantly, there was a good agreement between HA content determined by the SPR-based potency assay and the traditional SRID assay. Published by Elsevier Ltd. C1 [Khurana, Surender; King, Lisa R.; Manischewitz, Jody; Coyle, Elizabeth M.; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Khurana, S (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM surender.khurana@fda.hhs.gov FU BARDA/HHS FX This project was supported in part by IDDA funding from BARDA/HHS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Carol Weiss Manju Joshi, and Steven Rubin for thorough review of the manuscript. NR 40 TC 5 Z9 5 U1 6 U2 30 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 17 PY 2014 VL 32 IS 19 BP 2188 EP 2197 DI 10.1016/j.vaccine.2014.02.049 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AG7XN UT WOS:000335632200009 PM 24613520 ER PT J AU Sultana, I Yang, K Getie-Kebtie, M Couzens, L Markoff, L Alterman, M Eichelberger, MC AF Sultana, Ishrat Yang, Kevin Getie-Kebtie, Melkamu Couzens, Laura Markoff, Lewis Alterman, Michail Eichelberger, Maryna C. TI Stability of neuraminidase in inactivated influenza vaccines SO VACCINE LA English DT Article DE Influenza; Vaccines; Neuraminidase; Stability; Immunogenicity ID MASS-SPECTROMETRY; VIRUS NEURAMINIDASE; N2 NEURAMINIDASE; ANTIBODY; QUANTIFICATION; HEMAGGLUTININ; RECOMBINANT; INFECTION; IMMUNITY; HUMANS AB Influenza vaccines are effective in protecting against illness and death caused by this seasonal pathogen. Antibodies that block the function of either hemagglutinin (HA) or neuraminidase (NA) contribute to vaccine efficacy, however vaccine potency is based only on HA content. NA protein content in vaccines varies from season to season due to differences in the relative amounts of HA and NA in influenza A, H1N1 and H3N2, and influenza B viruses that are selected for each manufacturing campaign. This, as well as potential inherent differences in NA immunogenicity, may result in varying responses from year to year. Moreover, the antigenic stability of NA is likely to dictate whether similar antibody responses will be obtained to this antigen throughout the shelf-life of the vaccine. To address this factor, we subjected NAs of influenza A (subtypes N1 and N2) and B viruses to denaturing conditions to evaluate the stability of enzyme activity. Each NA type/subtype had unique sensitivity to denaturing conditions. The N2 enzyme activity was more thermostable than that of N1 or influenza B, while the NA activity of influenza B was most resistant to detergent. N1 enzyme activity was most resistant of the three NAs to freeze-thaw cycling. In these experiments, enzyme activity was indicative of the immunogenicity of NA, but was strain-dependent, with greater neuraminidase inhibiting (NI) antibody titers elicited following immunization with the 2009 HI NI pandemic virus A/California/7/2009, than the previously circulating seasonal H1 N1 strain, A/Brisbane/59/2007. Robust NI antibody titers against both N1 and N2 components were induced following vaccination of mice with a trivalent inactivated influenza vaccine. When stored under recommended conditions, the NA of both N1 and N2 subtypes remained immunogenic well after the vaccine expiry date. Published by Elsevier Ltd. C1 [Sultana, Ishrat; Yang, Kevin; Couzens, Laura; Markoff, Lewis; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20814 USA. [Getie-Kebtie, Melkamu; Alterman, Michail] US FDA, Div Cellular & Gene Therapies, Off Cell Tissue & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Eichelberger, MC (reprint author), US FDA, Div Viral Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20814 USA. EM Maryna.Eichelberger@fda.hhs.gov OI Alterman, Michail/0000-0003-3830-1813 FU Oak Ridge Institute for Science and Education FX We are indebted to CSL and Novartis for supplies of vaccines and intermediates used in this study. We thank Tracie Williams for generously providing advice and standards for mass spectrometry and the staff of the Division of Veterinary Services, CBER, FDA, for excellent animal care. Vladimir Lugovtsev and Falko Schmeisser provided helpful suggestions during the preparation of this manuscript. Intramural FDA funds were used to perform this project; IS and KY were supported by training funds administered by the Oak Ridge Institute for Science and Education. NR 19 TC 8 Z9 8 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 17 PY 2014 VL 32 IS 19 BP 2225 EP 2230 DI 10.1016/j.vaccine.2014.01.078 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AG7XN UT WOS:000335632200014 PM 24613525 ER PT J AU Malik, SM Maher, VE Bijwaard, KE Becker, RL Zhang, LJ Tang, SHW Song, PF Liu, Q Marathe, A Gehrke, B Helms, W Hanner, D Justice, R Pazdur, R AF Malik, Shakun M. Maher, Virginia Ellen Bijwaard, Karen E. Becker, Robert L. Zhang, Lijun Tang, Shenghui W. Song, Pengfei Liu, Qi Marathe, Anshu Gehrke, Brenda Helms, Whitney Hanner, Diane Justice, Robert Pazdur, Richard TI US Food and Drug Administration Approval: Crizotinib for Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer That Is Anaplastic Lymphoma Kinase Positive SO CLINICAL CANCER RESEARCH LA English DT Article ID EML4-ALK FUSION GENE; ALK; CHEMOTHERAPY; TRANSCRIPTS; CARCINOMAS; EGFR AB On August 26, 2011, the U. S. Food and Drug Administration (FDA) approved crizotinib (XALKORI Capsules, Pfizer Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as detected by an FDA-approved test. The Vysis ALK Break-Apart FISH Probe Kit (Abbott Molecular, Inc.) was approved concurrently. In two multicenter, single-arm trials, patients with locally advanced or metastatic ALK-positive NSCLC previously treated with one or more systemic therapies received crizotinib orally at a dose of 250 mg twice daily. In 119 patients with ALK-positive NSCLC by local trial assay, the objective response rate (ORR) was 61% [95% confidence intervals (CI), 52%-70%] with a median response duration of 48 weeks. In 136 patients with ALK-positive NSCLC by the to-be-marketed test, the ORR was 50% (95% CI, 42%-59%) with a median response duration of 42 weeks. The most common adverse reactions (>= 25%) were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Accelerated approval was granted on the basis of the high ORRs and durable responses. On November 20, 2013, crizotinib received full approval based on an improvement in progression-free survival in patients with metastatic ALK-positive NSCLC previously treated with one platinum-based chemotherapy regimen. Clin Cancer Res; 20(8); 2029-34. (C) 2014 AACR. C1 [Malik, Shakun M.] NCI, Clin Investigat Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. [Maher, Virginia Ellen; Gehrke, Brenda; Helms, Whitney; Hanner, Diane; Justice, Robert; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Silver Spring, MD 20993 USA. [Zhang, Lijun; Tang, Shenghui W.] US FDA, Off Biostat, Silver Spring, MD 20993 USA. [Song, Pengfei; Liu, Qi; Marathe, Anshu] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Bijwaard, Karen E.; Becker, Robert L.] US FDA, Off In Vitro Diagnost & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Justice, R (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 22,Room 2125, Silver Spring, MD 20993 USA. EM robert.justice@fda.hhs.gov NR 17 TC 41 Z9 41 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2014 VL 20 IS 8 BP 2029 EP 2034 DI 10.1158/1078-0432.CCR-13-3077 PG 6 WC Oncology SC Oncology GA AF3AJ UT WOS:000334583500004 PM 24573551 ER PT J AU Rouse, R Xu, L Stewart, S Zhang, J AF Rouse, Rodney Xu, Lin Stewart, Sharron Zhang, Jun TI High fat diet and GLP-1 drugs induce pancreatic injury in mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Acinar cell death; Drug-induced pancreatitis; High fat diet; Pro-inflammatory cytokines; Macrophage activation; Pancreatic vasculitis ID GLUCAGON-LIKE PEPTIDES; EXOCRINE PANCREAS; EXENATIDE; RATS; SITAGLIPTIN; ENDOCRINE; SEVERITY; OBESITY; INFLAMMATION; POPULATION AB Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNF alpha, IL-1 beta, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment. Published by Elsevier Inc. C1 [Rouse, Rodney; Xu, Lin; Stewart, Sharron; Zhang, Jun] US FDA, Div Appl Regulatory Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Rouse, R (reprint author), Bldg 64,Room 2088,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM rodney.rouse@fda.hhs.gov NR 60 TC 11 Z9 12 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR 15 PY 2014 VL 276 IS 2 BP 104 EP 114 DI 10.1016/j.taap.2014.01.021 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AF6JR UT WOS:000334821900003 PM 24534256 ER PT J AU Uslu, K Coleman, AS Allman, WR Katsenelson, N Bram, RJ Alugupalli, KR Akkoyunlu, M AF Uslu, Kadriye Coleman, Adam S. Allman, Windy R. Katsenelson, Nora Bram, Richard J. Alugupalli, Kishore R. Akkoyunlu, Mustafa TI Impaired B Cell Receptor Signaling Is Responsible for Reduced TACI Expression and Function in X-Linked Immunodeficient Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BRUTONS TYROSINE KINASE; NF-KAPPA-B; COMMON VARIABLE IMMUNODEFICIENCY; DEFICIENT MICE; MARGINAL ZONE; BAFF-R; TRANSMEMBRANE ACTIVATOR; ALTERNATE PATHWAY; ACCESSORY CELLS; IMMUNE-RESPONSE AB Immune response to T cell independent type 2 (TI-2) Ags, such as bacterial polysaccharides, is severely impaired in X-linked immunodeficient (XID) mice. In this study, we investigated the involvement of a proliferation-inducing ligand (APRIL) or BAFF and their receptors in the unresponsiveness of XID mouse to TI-2 Ags. We discovered that whereas serum BAFF levels were increased, the expression of the APRIL and BAFF receptor transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) was severely reduced in XID B cells. Moreover, B cells from XID mouse were unable to secrete Igs in response to APRIL or BAFF. In correlation with reduced TACI expression and impaired TACI function, APRIL or BAFF did not activate the classical NF-kappa B pathway in XID cells. Also correlating with the unaltered expression of BAFF receptor, BAFF stimulation induced the activation of the alternative NF-kappa B pathway in XID cells. Moreover, activation of MAPK pathway was ablated in APRIL-stimulated XID cells. Prestimulation of XID B cells with the TLR9 agonist, CpG led to a significant increase in TACI expression and restored TACI-mediated functions. CpG prestimulation also restored TACI-mediated signaling in APRIL-or BAFF-stimulated XID B cells. Finally, immunization of XID mouse with the prototype TI-2 Ag NP-Ficoll induced IgG and IgM Abs when CpG was given with NP-Ficoll. Collectively, these results suggest that reduced TACI expression is responsible for the unresponsiveness of XID mouse to TI-2 Ags and BCR activation controls TACI expression. C1 [Uslu, Kadriye; Coleman, Adam S.; Allman, Windy R.; Katsenelson, Nora; Akkoyunlu, Mustafa] US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. [Bram, Richard J.] Mayo Clin, Coll Med, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA. [Bram, Richard J.] Thomas Jefferson Univ, Dept Microbiol & Immunol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. RP Akkoyunlu, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. EM Mustafa.Akkoyunlu@fda.hhs.gov FU U.S. Food and Drug Administration; Oak Ridge Institute for Science, Oak Ridge, TN FX This work was supported by intramural grants from the U.S. Food and Drug Administration (to M.A.) and by postdoctoral fellowships from the Oak Ridge Institute for Science, Oak Ridge, TN (to K.U., A.S.C., and W.R.A.). NR 74 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2014 VL 192 IS 8 BP 3582 EP 3595 DI 10.4049/jimmunol.1203468 PG 14 WC Immunology SC Immunology GA AE9GB UT WOS:000334312900014 PM 24646744 ER PT J AU Sun, WJ Larsen, MD Lachin, JM AF Sun, Wanjie Larsen, Michael D. Lachin, John M. TI Methods for a longitudinal quantitative outcome with a multivariate Gaussian distribution multi-dimensionally censored by therapeutic intervention SO STATISTICS IN MEDICINE LA English DT Article DE Monte Carlo EM; censored normal regression; truncated MVN; non-ignorable missingness; multiple imputation; rescue medication ID MIXED-EFFECTS MODELS; DIASTOLIC BLOOD-PRESSURE; HIV VIRAL LOADS; EM ALGORITHM; MAXIMUM-LIKELIHOOD; CLINICAL-TRIALS; MEDICATION USE; MISSING DATA; IMPUTATION; POLYMORPHISM AB In longitudinal studies, a quantitative outcome (such as blood pressure) may be altered during follow-up by the administration of a non-randomized, non-trial intervention (such as anti-hypertensive medication) that may seriously bias the study results. Current methods mainly address this issue for cross-sectional studies. For longitudinal data, the current methods are either restricted to a specific longitudinal data structure or are valid only under special circumstances. We propose two new methods for estimation of covariate effects on the underlying (untreated) general longitudinal outcomes: a single imputation method employing a modified expectation-maximization (EM)-type algorithm and a multiple imputation (MI) method utilizing a modified Monte Carlo EM-MI algorithm. Each method can be implemented as one-step, two-step, and full-iteration algorithms. They combine the advantages of the current statistical methods while reducing their restrictive assumptions and generalizing them to realistic scenarios. The proposed methods replace intractable numerical integration of a multi-dimensionally censored MVN posterior distribution with a simplified, sufficiently accurate approximation. It is particularly attractive when outcomes reach a plateau after intervention due to various reasons. Methods are studied via simulation and applied to data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study of treatment for type 1 diabetes. Methods proved to be robust to high dimensions, large amounts of censored data, low within-subject correlation, and when subjects receive non-trial intervention to treat the underlying condition only (with high Y), or for treatment in the majority of subjects (with high Y) in combination with prevention for a small fraction of subjects (with normal Y). Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Sun, Wanjie] US FDA, Div Biometr 6, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. [Larsen, Michael D.; Lachin, John M.] George Washington Univ, Biostatsit Ctr, Rockville, MD 20852 USA. [Larsen, Michael D.; Lachin, John M.] George Washington Univ, Dept Stat, Rockville, MD 20852 USA. [Lachin, John M.] George Washington Univ, Dept Biostat & Epidemiol, Rockville, MD 20852 USA. RP Sun, WJ (reprint author), US FDA, Div Biometr 6, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. EM wanjie.sun@fda.hhs.gov OI Lachin, John/0000-0001-9838-2841 NR 47 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD APR 15 PY 2014 VL 33 IS 8 BP 1288 EP 1306 DI 10.1002/sim.6037 PG 19 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA AD1TS UT WOS:000333017100003 PM 24258796 ER PT J AU Shatzkes, K Teferedegne, B Murata, H AF Shatzkes, Kenneth Teferedegne, Belete Murata, Haruhiko TI A simple, inexpensive method for preparing cell lysates suitable for downstream reverse transcription quantitative PCR SO SCIENTIFIC REPORTS LA English DT Article ID RIBONUCLEASE INHIBITOR AB Sample nucleic acid purification can often be rate-limiting for conventional quantitative PCR (qPCR) workflows. We recently developed high-throughput virus microneutralization assays using an endpoint assessment approach based on reverse transcription qPCR (RT-qPCR). The need for cumbersome RNA purification is circumvented in our assays by making use of a commercial reagent that can easily generate crude cell lysates amenable to direct analysis by one-step RT-qPCR. In the present study, we demonstrate that a simple buffer containing a non-ionic detergent can serve as an inexpensive alternative to commercially available reagents for the purpose of generating RT-qPCR-ready cell lysates from MDCK cells infected with influenza virus. We have found that addition of exogenous RNase inhibitor as a buffer component is not essential in order to maintain RNA integrity, even following stress at 37 degrees C incubation for 1-2 hours, in cell-lysate samples either freshly prepared or previously stored frozen at -80 degrees C. C1 [Shatzkes, Kenneth; Teferedegne, Belete; Murata, Haruhiko] FDA, CBER, OVRR, Div Viral Prod,Lab DNA Viruses, Bethesda, MD 20892 USA. [Shatzkes, Kenneth] FDA, CBER, OVRR, Div Viral Prod,Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. RP Murata, H (reprint author), FDA, CBER, OVRR, Div Viral Prod,Lab DNA Viruses, Bethesda, MD 20892 USA. EM haruhiko.murata@fda.hhs.gov OI Shatzkes, Kenneth/0000-0002-1603-5326 FU Division of Microbiology and Infectious Diseases (DMID, NIAID, NIH, USA) [224-10-1018]; Oak Ridge Institute for Science and Education Fellowship through DMID FX This study was funded in part by a contract (Interagency Agreement Number 224-10-1018) from the Division of Microbiology and Infectious Diseases (DMID, NIAID, NIH, USA). We thank Sonnie Kim Grossman (DMID) for her support. K.S. was supported by an Oak Ridge Institute for Science and Education Fellowship through funds provided by DMID. We are grateful to Keith Peden and Andrew M. Lewis Jr. for comments on the manuscript. NR 17 TC 4 Z9 4 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 11 PY 2014 VL 4 AR 4659 DI 10.1038/srep04659 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6KW UT WOS:000334102200012 PM 24722424 ER PT J AU Tsang, JS Schwartzberg, PL Kotliarov, Y Biancotto, A Xie, Z Germain, RN Wang, E Olnes, MJ Narayanan, M Golding, H Moir, S Dickler, HB Perl, S Cheung, F AF Tsang, John S. Schwartzberg, Pamela L. Kotliarov, Yuri Biancotto, Angelique Xie, Zhi Germain, Ronald N. Wang, Ena Olnes, Matthew J. Narayanan, Manikandan Golding, Hana Moir, Susan Dickler, Howard B. Perl, Shira Cheung, Foo CA Baylor HIPC Ctr CHI Consortium TI Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses SO CELL LA English DT Article ID PLASMA-CELL DIFFERENTIATION; UNFOLDED PROTEIN RESPONSE; H1N1 INFLUENZA VACCINE; YELLOW-FEVER VACCINE; SYSTEMS BIOLOGY; GENE-EXPRESSION; B-CELLS; SEASONAL INFLUENZA; ANTIBODY; IMMUNIZATION AB A major goal of systems biology is the development of models that accurately predict responses to perturbation. Constructing such models requires the collection of dense measurements of system states, yet transformation of data into predictive constructs remains a challenge. To begin to model human immunity, we analyzed immune parameters in depth both at baseline and in response to influenza vaccination. Peripheral blood mononuclear cell transcriptomes, serum titers, cell subpopulation frequencies, and B cell responses were assessed in 63 individuals before and after vaccination and were used to develop a systematic framework to dissect inter- and intra-individual variation and build predictive models of postvaccination antibody responses. Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation cell populations alone, which were validated using independent baseline time points. Most of the parameters contributing to prediction delineated temporally stable baseline differences across individuals, raising the prospect of immune monitoring before intervention. C1 [Tsang, John S.; Schwartzberg, Pamela L.; Kotliarov, Yuri; Biancotto, Angelique; Xie, Zhi; Germain, Ronald N.; Wang, Ena; Olnes, Matthew J.; Dickler, Howard B.; Perl, Shira; Cheung, Foo] NIH, Trans NIH Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. [Tsang, John S.; Narayanan, Manikandan] NIAID, Lab Syst Biol, Syst Genom & Bioinformat Unit, NIH, Bethesda, MD 20892 USA. [Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Wang, Ena] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Olnes, Matthew J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Golding, Hana] US FDA, Lab Retrovirus Res, Bethesda, MD 20892 USA. [Moir, Susan] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Tsang, JS (reprint author), NIH, Trans NIH Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. EM john.tsang@nih.gov; pams@nhgri.nih.gov RI Pos, Zoltan/C-3623-2014; Kotliarov, Yuri/B-6938-2017 OI Pos, Zoltan/0000-0002-2574-7616; FU NIAID; NCI; NHLBI; NIAMS; NICHD; NIDDK; NINDS; NIEHS; NEI; NHGRI FX We thank M. Connors, K. Subbarao, R. Seder, M. Roederer, D. Douek, J. Bennink, I. Fraser, J. Mandl, members of the Systems Genomics and Bioinformatics Unit (NIAID), and M. Eichelberger (FDA) for helpful advice and feedback; the staff of the NIH Clinical Center for outstanding clinical support; and NIAID's high-performance computing team for outstanding support. This work is funded by the Intramural Programs of NIAID, NCI, NHLBI, NIAMS, NICHD, NIDDK, NINDS, NIEHS, NEI, and NHGRI. NR 41 TC 76 Z9 76 U1 1 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 10 PY 2014 VL 157 IS 2 BP 499 EP 513 DI 10.1016/j.cell.2014.03.031 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AE9DK UT WOS:000334304500021 PM 24725414 ER PT J AU Shah, RB Yang, YS Khan, MA Raw, A Yu, LX Faustino, PJ AF Shah, Rakhi B. Yang, Yongsheng Khan, Mansoor A. Raw, Andre Yu, Lawrence X. Faustino, Patrick J. TI Pharmaceutical characterization and thermodynamic stability assessment of a colloidal iron drug product: Iron sucrose SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Colloid; Formulation; Nanoparticles; Stability; Chromatography; Thermodynamic stability ID SODIUM FERRIC GLUCONATE; THERAPY; DEXTRAN AB The study objective was to evaluate the thermodynamic stability of iron sucrose complexes as determined by molecular weight (m.w.) changes. The first part of the study focused on the effect of thermal stress, pH, electrolyte or excipient dilution on the stability of a colloidal iron drug product. Part two focused on the physical and chemical evaluation of the colloidal nature of iron sucrose using a series of characterization experiments: ultracentrifugation, dialysis, particle size, zeta potential, and osmotic pressure analysis. A validated Taguchi-optimized high performance gel permeation chromatography method was used for m.w. determinations. Results indicate m.w. of the iron sucrose complex remained unchanged after excipient dilution, ultracentrifugation, dialysis, and electrolyte dilution. Electrolyte dilution studies indicated the lyophilic nature of the iron sucrose colloid with a particle size of 10 nm and zeta potential of 0mV. The complex deformed at low pH and reformed back at the formulation pH. The complex is stable under mild-to-moderate temperature <50 degrees C but aggregates following prolonged exposure to high temperatures >70 degrees C. In conclusion, the resistance of the complex to breakdown by electrolytic conditions, excipient dilution, ultracentrifugation and the reversible complexation after alteration of formulation pH suggest iron sucrose is a lyophilic colloid in nature and lyophilic colloidals are thermodynamically stable. Published by Elsevier B.V. C1 [Shah, Rakhi B.; Yang, Yongsheng; Khan, Mansoor A.; Faustino, Patrick J.] US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. [Raw, Andre; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. RP Faustino, PJ (reprint author), 10903 New Hampshire Ave,LS Bldg 64, Silver Spring, MD 20993 USA. EM Patrick.Faustino@fda.hhs.gov NR 9 TC 2 Z9 2 U1 1 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 EI 1873-3476 J9 INT J PHARMACEUT JI Int. J. Pharm. PD APR 10 PY 2014 VL 464 IS 1-2 BP 46 EP 52 DI 10.1016/j.ijpharm.2014.01.008 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB3YL UT WOS:000331726000006 PM 24440404 ER PT J AU Buzatu, DA Moskal, TJ Williams, AJ Cooper, WM Mattes, WB Wilkes, JG AF Buzatu, Dan A. Moskal, Ted J. Williams, Anna J. Cooper, Willie Mae Mattes, William B. Wilkes, Jon G. TI An Integrated Flow Cytometry-Based System for RealTime, High Sensitivity Bacterial Detection and Identification SO PLOS ONE LA English DT Article ID ESCHERICHIA-COLI O157-H7; FOOD MATRIX INTERFERENCE; SAMPLE PREPARATION; PCR DETECTION; SAFETY; COMBINATION; SALMONELLA; PATHOGENS; ANTIBODY; CULTURE AB Foodborne illnesses occur in both industrialized and developing countries, and may be increasing due to rapidly evolving food production practices. Yet some primary tools used to assess food safety are decades, if not centuries, old. To improve the time to result for food safety assessment a sensitive flow cytometer based system to detect microbial contamination was developed. By eliminating background fluorescence and improving signal to noise the assays accurately measure bacterial load or specifically identify pathogens. These assays provide results in minutes or, if sensitivity to one cell in a complex matrix is required, after several hours enrichment. Conventional assessments of food safety require 48 to 56 hours. The assays described within are linear over 5 orders of magnitude with results identical to culture plates, and report live and dead microorganisms. This system offers a powerful approach to real-time assessment of food safety, useful for industry self-monitoring and regulatory inspection. C1 [Buzatu, Dan A.; Williams, Anna J.; Cooper, Willie Mae; Wilkes, Jon G.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Moskal, Ted J.] Vivione Biosci, Pine Bluff, AR USA. [Mattes, William B.] PharmPoint Consulting, Poolesville, MD USA. RP Buzatu, DA (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM dan.buzatu@fda.hhs.gov NR 34 TC 11 Z9 11 U1 2 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2014 VL 9 IS 4 DI 10.1371/journal.pone.0094254 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE9PC UT WOS:000334339000096 ER PT J AU Zhou, ZH Karnaukhova, E Rajabi, M Reeder, K Chen, TN Dhawan, S Kozlowski, S AF Zhou, Zhao-Hua Karnaukhova, Elena Rajabi, Mohsen Reeder, Kelly Chen, Trina Dhawan, Subhash Kozlowski, Steven TI Oversulfated Chondroitin Sulfate Binds to Chemokines and Inhibits Stromal Cell- Derived Factor-1 Mediated Signaling in Activated T Cells SO PLOS ONE LA English DT Article ID HEPARIN-INDUCED THROMBOCYTOPENIA; ADVERSE CLINICAL EVENTS; SDF-1; RECEPTOR; CXCR4; GLYCOSAMINOGLYCANS; FACTOR-1-ALPHA; MOBILIZATION; INFLAMMATION; TRAFFICKING AB Oversulfated chondroitin sulfate (OSCS), a member of the glycosaminoglycan (GAG) family, was a contaminant in heparin that was linked to the 2008 heparin adverse events in the US. Because of its highly negative charge, OSCS can interact with many components of the contact and immune systems. We have previously demonstrated that OSCS inhibited the complement classical pathway by binding C1 inhibitor and potentiating its interaction with C1s. In the present study, by using surface plasmon resonance, we found OSCS interacts with T cell chemokines that can impact adaptive immunity. The binding of OSCS to stromal cell-derived factor-1 (SDF-1) chemokines, SDF-1 alpha and SDF-1 beta, caused a significant change in the secondary structures of these chemokines as detected by far- ultraviolet circular dichroism spectra analysis. Functionally, OSCS binding profoundly inhibited SDF-1-induced calcium mobilization and T cell chemotaxis. Imaging flow cytometry revealed T cell morphological changes mediated by SDF-1 alpha were completely blocked by OSCS. We conclude that the OSCS, a past contaminant in heparin, has broad interactions with the components of the human immune system beyond the contact and complement systems, and that may explain, in part, prior OSCS-related adverse events, while suggesting potentially useful therapeutic applications for related GAGs in the control of inflammation. C1 [Zhou, Zhao-Hua; Reeder, Kelly; Chen, Trina; Kozlowski, Steven] US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20014 USA. [Karnaukhova, Elena] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20014 USA. [Rajabi, Mohsen] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Therapeut Proteins,Off Biotechnol, Bethesda, MD 20014 USA. [Dhawan, Subhash] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. RP Kozlowski, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20014 USA. EM Steven.Kozlowski@fda.hhs.gov FU Intramural Research Program of the US Food and Drug Administration FX This research was supported by the Intramural Research Program of the US Food and Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 1 Z9 2 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2014 VL 9 IS 4 AR e94402 DI 10.1371/journal.pone.0094402 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE9PC UT WOS:000334339000118 PM 24718687 ER PT J AU Eapen, ZJ Lauer, MS Temple, RJ AF Eapen, Zubin J. Lauer, Michael S. Temple, Robert J. TI The Imperative of Overcoming Barriers to the Conduct of Large, Simple Trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Eapen, Zubin J.] Duke Clin Res Inst, Durham, NC 27715 USA. [Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Temple, Robert J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Eapen, ZJ (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM zubin.eapen@duke.edu FU FDA HHS [U19FD003800] NR 5 TC 28 Z9 29 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 9 PY 2014 VL 311 IS 14 BP 1397 EP 1398 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AE4EP UT WOS:000333935000012 PM 24715072 ER PT J AU Wang, X Tan, JY Zhao, JQ Ye, ZP Hewlett, I AF Wang, Xue Tan, Jiying Zhao, Jiangqin Ye, Zhiping Hewlett, Indira TI Highly pathogenic avian influenza A virus (H5N1) can be transmitted in ferrets by transfusion SO BMC INFECTIOUS DISEASES LA English DT Article DE H5N1; Transfusion; Viremia; Ferrets ID PANDEMIC INFLUENZA; ACTIVATION; INFECTION; POULTRY; VIREMIA; HUMANS; HEALTH; CELLS; CHILD AB Background: Highly pathogenic avian influenza A virus has been shown to infect organs other than the lung, and this is likely to be mediated by systemic spread resulting from viremia which has been detected in blood in severe cases of infection with avian H5N1 viruses. The infectivity of virus in blood and the potential for virus transmission by transfusion has not been investigated. Methods: Using a susceptible ferret animal model, we evaluated viremia and transmission by blood transfusion. Blood was collected on day 2, 4, 6, and 10 post-infection (or before death) from donor ferrets infected with either low dose (1.0 x 10(2.6) EID50/ml) or high dose (1.0 x 10(3.6) EID50/ml) of H5N1 virus, A/VN/1203/04 and transfused to recipient animals. Results: Viremia was observed in 2/12 (16.67%) recipients that received blood from donor ferrets infected with low dose and 7/12 (58.33%) recipients who received blood from high dose infected donors. 1/12 (8.3%) low dose recipients and 6/12 (50%) high dose recipients died within 11 days after transfusion. Increased changes in body weight and temperatures were observed in high dose recipients, and high levels of viral RNA were detected in recipient ferrets after transfusion of blood from the early viremic phase, which also correlated with adverse impact on their survival. Conclusion: These data suggest that highly pathogenic avian influenza A virus, H5N1, is transmissible by blood transfusion in ferrets. Low levels of viremia were detected around the time of onset of symptoms and later in ferrets infected with highly pathogenic H5N1 virus. These findings may have implication for pathogenesis and transmissibility of H5N1. C1 [Wang, Xue; Tan, Jiying; Zhao, Jiangqin; Hewlett, Indira] CBER FDA, Div Emerging & Transfus Transmitted Dis, Lab Mol Virol, Bethesda, MD 20892 USA. [Ye, Zhiping] Food & Drug Adm, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Wang, X (reprint author), CBER FDA, Div Emerging & Transfus Transmitted Dis, Lab Mol Virol, Bldg 29B,Rm 4NN22,8800 Rockville Pike, Bethesda, MD 20892 USA. EM xue.wang@fda.hhs.gov; indira.hewlett@fda.hhs.gov FU CBER FX The authors wish to acknowledge Dr. Mingjie Zhang, Dr. Krishna Devadas and Dr. Robin Biswas for their critical review of this manuscript. The authors also wish to acknowledge BIOQUAL, Inc. (Rockville, MD) for performing the animal infections. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. This work was funded by an intramural grant from CBER in FDA. NR 28 TC 10 Z9 12 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD APR 8 PY 2014 VL 14 AR 192 DI 10.1186/1471-2334-14-192 PG 10 WC Infectious Diseases SC Infectious Diseases GA AG5QF UT WOS:000335472900001 PM 24712669 ER PT J AU Chaudhury, A Wu, HQ Khan, M Ramachandran, R AF Chaudhury, Anwesha Wu, Huiquan Khan, Mansoor Ramachandran, Rohit TI A mechanistic population balance model for granulation processes: Effect of process and formulation parameters SO CHEMICAL ENGINEERING SCIENCE LA English DT Article DE Granulation; Multi-dimensional population balance model; Induction growth; Mechanistic model; Aggregation kernel ID HIGH-SHEAR GRANULATION; LIQUID-BOUND GRANULES; WET GRANULATION; PARTICULATE PROCESSES; NUMERICAL-SOLUTION; QUADRATURE METHOD; REGIME MAP; CRYSTALLIZATION; AGGLOMERATION; NUCLEATION AB This work is concerned with the theoretical development of a semi mechanistic aggregation kernel in a population balance model (PBM) which takes into account the effect of droplet spreading on a particle surface that aids in the coalescence of particles. Empirical aggregation kernels are more commonly used in simulations however they do not reflect the true physics of the system. The proposed kernel is computationally less expensive, yet it takes into account the various key operating parameters that affect the process. The kernel has been validated qualitatively and the lumped and distributed properties show good agreement with the expected behavior of the process. The various empirical parameters present in the granulation model have been identified and expressed as a function of the measurable operating quantities, thus providing a better knowledge regarding the effect of the process parameters on the final product with the help of a more fundamental, first principle based model. A detailed sensitivity analysis (involving viscosity, impeller speed, contact angle and liquid spray rate) has also been conducted in order to study the influence of the process parameters on the final granule properties. This knowledge provides a theoretical basis for the high shear wet granulation process design space development. The model has also been able to successfully capture the steady and induction behavior of the process under the expected operating conditions. (C) 2013 Elsevier Ltd. All rights reserved C1 [Chaudhury, Anwesha; Ramachandran, Rohit] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08855 USA. [Wu, Huiquan; Khan, Mansoor] US FDA, Div Prod Qual Res HFD 940, Off Testing & Res, Off Pharmaceut Sci,CDER, Silver Spring, MD USA. RP Ramachandran, R (reprint author), Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08855 USA. EM rohit.r@rutgers.edu FU Ministry of Education [LH12115-MultiGRAN]; Specific University Research (project MSMT) [20/2013]; National Institute for Pharmaceutical Technology and Education (NIPTE); U.S. Food and Drug Administration (FDA) [5U01FD004275-02]; NSF-ECC [0540855]; various FDA FX The authors would like to acknowledge funding from the Ministry of Education (project LH12115-MultiGRAN) and the Specific University Research (project MSMT no. 20/2013), the National Institute for Pharmaceutical Technology and Education (NIPTE) and the U.S. Food and Drug Administration (FDA) for providing funds for this research via the FDA-sponsored grant Critical Path Manufacturing Sector Research Initiative (5U01FD004275-02). They would also like to thank the Engineering Research Center for Structured Organic Particulate Systems (ERC C-SOPS) through grant NSF-ECC 0540855. The support from various FDA personnel including Dr. R. Lostritto, Dr. V. Vilker, Cheryl Kaiser, Mr. J. Clark and Dr. C. Buhse are acknowledged. NR 55 TC 15 Z9 15 U1 1 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-2509 EI 1873-4405 J9 CHEM ENG SCI JI Chem. Eng. Sci. PD APR 7 PY 2014 VL 107 BP 76 EP 92 DI 10.1016/j.ces.2013.11.031 PG 17 WC Engineering, Chemical SC Engineering GA 302BO UT WOS:000330576500007 ER PT J AU Chatham-Stephens, K Law, R Taylor, E Melstrom, P Bunnell, R Wang, BG Apelberg, B Schier, JG AF Chatham-Stephens, Kevin Law, Royal Taylor, Ethel Melstrom, Paul Bunnell, Rebecca Wang, Baoguang Apelberg, Benjamin Schier, Joshua G. TI Calls to Poison Centers for Exposures to Electronic Cigarettes - United States, September 2010-February 2014 SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article C1 [Chatham-Stephens, Kevin] CDC, Atlanta, GA 30333 USA. [Law, Royal; Taylor, Ethel; Schier, Joshua G.] CDC, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. [Melstrom, Paul; Bunnell, Rebecca] CDC, Off Smoking & Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Wang, Baoguang; Apelberg, Benjamin] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. RP Chatham-Stephens, K (reprint author), CDC, Atlanta, GA 30333 USA. EM xdc4@cdc.gov FU NIH HHS [T35 OD010991] NR 5 TC 69 Z9 70 U1 0 U2 10 PU CENTER DISEASE CONTROL & PREVENTION PI ATLANTA PA MAILSTOP E-90, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD APR 4 PY 2014 VL 63 IS 13 BP 292 EP 293 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AE1TD UT WOS:000333752000004 PM 24699766 ER PT J AU Choi, MJ Jackson, KA Medus, C Beal, J Rigdon, CE Cloyd, TC Forstner, MJ Ball, J Bosch, S Bottichio, L Cantu, V Melka, DC Ishow, W Slette, S Irvin, K Wise, M Tarr, C Mahon, B Smith, KE Silk, BJ AF Choi, Mary J. Jackson, Kelly A. Medus, Carlota Beal, Jennifer Rigdon, Carrie E. Cloyd, Tami C. Forstner, Matthew J. Ball, Jill Bosch, Stacy Bottichio, Lyndsay Cantu, Venessa Melka, David C. Ishow, Wilete Slette, Sarah Irvin, Kari Wise, Matthew Tarr, Cheryl Mahon, Barbara Smith, Kirk E. Silk, Benjamin J. TI Multistate Outbreak of Listeriosis Linked to Soft-Ripened Cheese - United States, 2013 SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article C1 [Choi, Mary J.; Medus, Carlota; Smith, Kirk E.] Minnesota Dept Hlth, Minneapolis, MN 55414 USA. [Jackson, Kelly A.; Bosch, Stacy; Wise, Matthew; Tarr, Cheryl; Mahon, Barbara; Silk, Benjamin J.] CDC, Div Foodborne Waterborne & Environm Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Beal, Jennifer; Cloyd, Tami C.; Irvin, Kari] US FDA, Coordinated Outbreak Response & Evaluat Network, Rockville, MD 20857 USA. [Rigdon, Carrie E.; Forstner, Matthew J.] Minnesota Dept Agr, St Paul, MN USA. [Ball, Jill] Wisconsin Dept Agr Trade & Consumer Protect, Madison, WI USA. [Bottichio, Lyndsay] Ohio Dept Hlth, Columbus, OH 43266 USA. [Cantu, Venessa] Texas Dept State Hlth Serv, Austin, TX USA. [Melka, David C.] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. [Ishow, Wilete] Chicago Dept Publ Hlth, Chicago, IL USA. [Slette, Sarah] Indiana State Dept Hlth, Indianapolis, IN 46202 USA. RP Choi, MJ (reprint author), Minnesota Dept Hlth, Minneapolis, MN 55414 USA. EM mjchoi@cdc.gov NR 4 TC 7 Z9 8 U1 0 U2 8 PU CENTER DISEASE CONTROL & PREVENTION PI ATLANTA PA MAILSTOP E-90, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD APR 4 PY 2014 VL 63 IS 13 BP 294 EP 295 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AE1TD UT WOS:000333752000005 PM 24699767 ER PT J AU Genualdi, S Nyman, P Begley, T AF Genualdi, Susan Nyman, Patricia Begley, Timothy TI Updated evaluation of the migration of styrene monomer and oligomers from polystyrene food contact materials to foods and food simulants SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE styrene trimer; styrene dimer; polystyrene; diffusion coefficients; styrene monomer; food packaging; migration ID VOLATILE ORGANIC-COMPOUNDS; CHROMATOGRAPHIC DETERMINATION; SIMULATING SOLVENTS; GC-MS; TRIMERS; DIMERS; EXTRACTION; CONTAINERS; CUPS AB Due to the 2011 labelling of styrene monomer as "reasonably anticipated to be a human carcinogen" by the National Institutes of Health's National Toxicology Program (NTP) and the controversy over whether styrene oligomers mimic the physiological effects of estrogen, an updated review of styrene monomer and oligomers in food and food contact materials (FCMs) was performed. The concentrations of styrene monomer and oligomers were determined in 24 polystyrene (PS) products and ranged from 9.3 to 3100mgkg(-1) for the styrene monomer, 130-2900mgkg(-1) for the sum of three styrene dimers, and 220-16,000mgkg(-1) for the sum of six styrene trimers. Foods in contact with PS packaging had styrene monomer concentrations ranging from 2.6 to 163ngg(-1); dimer concentrations from the limit of quantitation (LOQ) to 4.8ngg(-1) and trimer concentrations were all below the LOQ (2ngg(-1)). Diffusion coefficients (D-p) and partition coefficients (K) were also calculated for styrene dimers and trimers. The results presented here indicate that styrene monomer concentrations in foods have not significantly changed since the 1980s and monomer concentrations in food packaging quantified in this study were all below USFDA limits. Although styrene dimers and trimers are present in higher concentrations in PS FCMs than the monomer, their migration to food is limited because of their high K values (4x10(2) to 2x10(6)) and their low diffusion coefficients in PS products. Additionally, diffusion coefficients calculated using USFDA-recommended food simulants and Arrhenius plots describing the temperature dependence of styrene dimers and trimers can be used in future calculations of dietary intake of the styrene oligomers. C1 [Genualdi, Susan; Nyman, Patricia; Begley, Timothy] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Genualdi, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM susan.genualdi@fda.hhs.gov NR 32 TC 5 Z9 5 U1 7 U2 43 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 EI 1944-0057 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PD APR 3 PY 2014 VL 31 IS 4 BP 723 EP 733 DI 10.1080/19440049.2013.878040 PG 11 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA AF6LT UT WOS:000334827300017 PM 24383702 ER PT J AU Haley, BJ Choi, SY Grim, CJ Onifade, TJ Cinar, HN Tall, BD Taviani, E Hasan, NA Abdullah, AH Carter, L Sahu, SN Kothary, MH Chen, A Baker, R Hutchinson, R Blackmore, C Cebula, TA Huq, A Colwell, RR AF Haley, Bradd J. Choi, Seon Young Grim, Christopher J. Onifade, Tiffiani J. Cinar, Hediye N. Tall, Ben D. Taviani, Elisa Hasan, Nur A. Abdullah, AbdulShakur H. Carter, Laurenda Sahu, Surasri N. Kothary, Mahendra H. Chen, Arlene Baker, Ron Hutchinson, Richard Blackmore, Carina Cebula, Thomas A. Huq, Anwar Colwell, Rita R. TI Genomic and Phenotypic Characterization of Vibrio cholerae Non-O1 Isolates from a US Gulf Coast Cholera Outbreak SO PLOS ONE LA English DT Article ID EL-TOR STRAINS; TOXIN-COREGULATED PILI; UNITED-STATES; VIRULENCE FACTORS; CTX PROPHAGE; INFECTIONS; BANGLADESH; DIARRHEA; DISEASE; CHITIN AB Between November 2010, and May 2011, eleven cases of cholera, unrelated to a concurrent outbreak on the island of Hispaniola, were recorded, and the causative agent, Vibrio cholerae serogroup O75, was traced to oysters harvested from Apalachicola Bay, Florida. From the 11 diagnosed cases, eight isolates of V. cholerae were isolated and their genomes were sequenced. Genomic analysis demonstrated the presence of a suite of mobile elements previously shown to be involved in the disease process of cholera (ctxAB, VPI-1 and -2, and a VSP-II like variant) and a phylogenomic analysis showed the isolates to be sister taxa to toxigenic V. cholerae V51 serogroup O141, a clinical strain isolated 23 years earlier. Toxigenic V. cholerae O75 has been repeatedly isolated from clinical cases in the southeastern United States and toxigenic V. cholerae O141 isolates have been isolated globally from clinical cases over several decades. Comparative genomics, phenotypic analyses, and a Caenorhabditis elegans model of infection for the isolates were conducted. This analysis coupled with isolation data of V. cholerae O75 and O141 suggests these strains may represent an underappreciated clade of cholera-causing strains responsible for significant disease burden globally. C1 [Haley, Bradd J.; Taviani, Elisa; Hasan, Nur A.; Chen, Arlene; Huq, Anwar; Colwell, Rita R.] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA. [Choi, Seon Young; Hasan, Nur A.; Abdullah, AbdulShakur H.; Cebula, Thomas A.; Colwell, Rita R.] CosmosID, College Pk, MD USA. [Grim, Christopher J.; Cinar, Hediye N.; Tall, Ben D.; Carter, Laurenda; Sahu, Surasri N.; Kothary, Mahendra H.] US FDA, CFSAN, DVA, Laurel, MD USA. [Onifade, Tiffiani J.; Hutchinson, Richard; Blackmore, Carina] Bur Environm Publ Hlth Med, Florida Dept Hlth, Tallahassee, FL USA. [Baker, Ron] Florida Dept Hlth Bur, Publ Hlth Labs, Jacksonville, FL USA. [Cebula, Thomas A.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Huq, Anwar] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. [Colwell, Rita R.] Univ Maryland, Inst Adv Comp Studies, College Pk, MD 20742 USA. [Colwell, Rita R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Colwell, RR (reprint author), Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA. EM rcolwell@umiacs.umd.edu OI Colwell, Rita R./0000-0001-5432-1502; Tall, Ben/0000-0003-0399-3629 FU National Science Foundation [0813066]; National Institutes of Health [2RO1A1039129-11A2]; National Institutes of Health-Fogarty International Center [1RC1TW008587-01]; National Oceanic and Atmospheric Administration [SO660009] FX This work was supported by a grant the National Science Foundation (www.nsf.gov), No. 0813066, National Institutes of Health (www.nih.gov) Grant 2RO1A1039129-11A2, National Institutes of Health-Fogarty International Center (http://www.fic.nih.gov) Challenge Grant 1RC1TW008587-01 and National Oceanic and Atmospheric Administration (www.noaa.gov) Grant No. SO660009. The funders provided salary and laboratory supplies only. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 7 Z9 7 U1 2 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 3 PY 2014 VL 9 IS 4 AR e86264 DI 10.1371/journal.pone.0086264 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6LR UT WOS:000334105000001 PM 24699521 ER PT J AU Parsons, LM Cipollo, J AF Parsons, Lisa M. Cipollo, John TI Oral ingestion of Microbacterium nematophilum leads to anal-region infection in Caenorhabditis elegans SO MICROBES AND INFECTION LA English DT Article DE Sodium azide; Ethanol; Cy3 dye; Caenorhabditus elegans; Microbacterium nematophilum; Infection model ID BACTERIAL PATHOGEN; INNATE IMMUNITY; SODIUM-AZIDE; RESISTANT; VIRULENCE; ADHESION; MUTANTS; GLYCANS; BINDING; PROTEIN AB Microbacterium nematophilum is a gram positive bacterium that colonizes the Caenorhabditis elegans rectal region causing swelling and constipation. This interaction has been exploited as a model system to identify and study genes important in host pathogen interactions and innate immunity. During attempts to inhibit the host pathogen interaction, it became important to clarify the route of infection. Using bacteria labeled with the fluorescent dye Cy3, we show that infection is via the oral route only and that infection follows a clear pattern of ingestion, plug formation, and bump development that can be quantitatively tracked over time. Published by Elsevier Masson SAS on behalf of Institut Pasteur. C1 [Parsons, Lisa M.; Cipollo, John] US FDA, Ctr Biol & Res, Bethesda, MD 20892 USA. RP Cipollo, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29,Room 126,8800 Rockville Pike, Bethesda, MD 20892 USA. EM john.cipollo@fda.hhs.gov NR 27 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 EI 1769-714X J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2014 VL 16 IS 4 BP 356 EP 361 DI 10.1016/j.micinf.2014.01.002 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AY9JN UT WOS:000347866400011 PM 24463271 ER PT J AU Andrews, K Palachuvattil, J Dang, P Gusev, P Savarala, S Pehrsson, P Harnly, J Dwyer, J Betz, J Saldanha, L Bailey, R Costello, R Gahche, J Hardy, C Emenaker, N AF Andrews, K. Palachuvattil, J. Dang, P. Gusev, P. Savarala, S. Pehrsson, P. Harnly, J. Dwyer, J. Betz, J. Saldanha, L. Bailey, R. Costello, R. Gahche, J. Hardy, C. Emenaker, N. TI Botanical initiative for the Dietary Supplement Ingredient Database: green tea pilot study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Gahche, J.] NHANES CDC NCHS, Hyattsville, MD USA. [Hardy, C.] CFSAN FDA, College Pk, MD USA. [Emenaker, N.] NCI NIH, Bethesda, MD USA. [Dwyer, J.; Betz, J.; Saldanha, L.; Bailey, R.; Costello, R.] ODS NIH, Bethesda, MD USA. [Harnly, J.] BHNRC FCMDL USDA ARS, Beltsville, MD USA. [Andrews, K.; Palachuvattil, J.; Dang, P.; Gusev, P.; Savarala, S.; Pehrsson, P.] BHNRC NDL USDA ARS, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 245.7 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700274 ER PT J AU Bhattacharyya, S Pence, L Yan, K Gill, P Letzig, L Simpson, P Beger, R James, L AF Bhattacharyya, Sudeepa Pence, Lisa Yan, Ke Gill, Pritmohinder Letzig, Lynda Simpson, Pippa Beger, Richard James, Laura TI Bile acids and acetaminophen protein adducts in children with acetaminophen overdose SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda; James, Laura] Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72202 USA. [Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda; James, Laura] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Yan, Ke; Simpson, Pippa] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Pence, Lisa; Beger, Richard] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 653.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702419 ER PT J AU Gusev, P Andrews, K Palachuvattil, J Dang, P Roseland, J Holden, J Savarala, S Pehrsson, P Dwyer, J Betz, J Saldanha, L Bailey, R Costello, R Gahche, J Hardy, C Emenaker, N Douglass, L AF Gusev, P. Andrews, K. Palachuvattil, J. Dang, P. Roseland, J. Holden, J. Savarala, S. Pehrsson, P. Dwyer, J. Betz, J. Saldanha, L. Bailey, R. Costello, R. Gahche, J. Hardy, C. Emenaker, N. Douglass, L. TI Over-the-counter prenatal multivitamin/mineral products: chemical analysis for the Dietary Supplement Ingredient Database SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Gahche, J.] CDC, NHANES, NCHS, Hyattsville, MD USA. [Douglass, L.] Consulting Statistician, Longmont, CO USA. [Hardy, C.] FDA, CFSAN, College Pk, MD USA. [Emenaker, N.] NCI, NIH, Bethesda, MD 20892 USA. [Dwyer, J.; Betz, J.; Saldanha, L.; Bailey, R.; Costello, R.] NIH, ODS, Bethesda, MD 20892 USA. [Gusev, P.; Andrews, K.; Palachuvattil, J.; Dang, P.; Roseland, J.; Holden, J.; Savarala, S.; Pehrsson, P.] ARS, BHNRC, NDL, USDA, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 809.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646704408 ER PT J AU Saldanha, L Dwyer, J Bailen, R Andrews, K Bailey, R Betz, J Burt, V Chang, F Costello, R Emenaker, N Gahche, J Harnly, J Hardy, C Pehrsson, P AF Saldanha, L. Dwyer, J. Bailen, R. Andrews, K. Bailey, R. Betz, J. Burt, V. Chang, F. Costello, R. Emenaker, N. Gahche, J. Harnly, J. Hardy, C. Pehrsson, P. TI When a dietary supplement product name says "energy", what's in the bottle? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Andrews, K.; Harnly, J.; Pehrsson, P.] USDA ARS, Beltsville, MD USA. [Hardy, C.] US FDA, CFSAN, College Pk, MD USA. [Emenaker, N.] NCI, NIH, Rockville, MD USA. [Burt, V.; Gahche, J.] CDC, NHANES, Hyattsville, MD USA. [Chang, F.] Natl Lib Med, NIH, Bethesda, MD USA. [Saldanha, L.; Dwyer, J.; Bailen, R.; Bailey, R.; Betz, J.; Costello, R.] NIH, ODS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 634.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646702298 ER PT J AU Sarntivijai, S Hur, J Ozgur, A Burkhart, K He, YQ Omenn, G Athey, B Abernethy, D AF Sarntivijai, Sirarat Hur, Junguk Ozgur, Arzucan Burkhart, Keith He, Yongqun Omenn, Gilbert Athey, Brian Abernethy, Darrell TI A systems pharmacology approach to model tyrosine kinase inhibitor-induced cardiotoxicity gene interaction networks SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Ozgur, Arzucan] Bogazici Univ, Dept Comp Sci, Istanbul, Turkey. [Burkhart, Keith; Abernethy, Darrell] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Omenn, Gilbert; Athey, Brian] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Hur, Junguk] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [He, Yongqun] Univ Michigan, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. RI Ozgur, Arzucan/I-3147-2012 OI Ozgur, Arzucan/0000-0001-8376-1056 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 844.17 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705134 ER PT J AU Unger, V Pope, C Flores, A DeFeo, C AF Unger, Vinzenz Pope, Christopher Flores, Adrian DeFeo, Christopher TI In the shadows of the membrane: A tale about how to beat the odds in cellular copper acquisition SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Unger, Vinzenz; Pope, Christopher; Flores, Adrian] Northwestern Univ, Dept Mol Biosci, Evanston, IL USA. [DeFeo, Christopher] USDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 360.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700476 ER PT J AU Anderson, A Granberg, E Kropp, J Peckham, J Condrasky, M Mroz, T Haley-Zitlin, V AF Anderson, Annie Granberg, Ellen Kropp, Jaclyn Peckham, Janet Condrasky, Marge Mroz, Tom Haley-Zitlin, Vivian TI The Effect of Gender and National School Lunch Program Participation on Saturated Fat Content of Entree Items Chosen by Elementary School-Aged Students SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Anderson, Annie; Granberg, Ellen; Condrasky, Marge; Mroz, Tom; Haley-Zitlin, Vivian] Clemson Univ, Clemson, SC USA. [Peckham, Janet] FDA, College Pk, MD USA. [Kropp, Jaclyn] Univ Florida, Gainesville, FL USA. RI Granberg, Ellen/J-7393-2015 OI Granberg, Ellen/0000-0001-5291-5315 NR 0 TC 0 Z9 0 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA LB379 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651004373 ER PT J AU De Felice, A Link, W Gatti, P AF De Felice, Albert Link, William Gatti, Philip TI Angiotensin receptor blockers are not carcinogenic in rodents SO FASEB JOURNAL LA English DT Meeting Abstract C1 [De Felice, Albert; Link, William; Gatti, Philip] US FDA, Div Cardiorenal Drug Prod, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1049.4 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000346 ER PT J AU Diack, AB Ritchie, DL Peden, AH Brown, D Boyle, A Morabito, L Maclennan, D Burgoyne, P Piccardo, P Ironside, JW Manson, JC AF Diack, Abigail B. Ritchie, Diane L. Peden, Alexander H. Brown, Deborah Boyle, Aileen Morabito, Laura Maclennan, David Burgoyne, Paul Piccardo, Pedro Ironside, James W. Manson, Jean C. TI Variable protease-sensitive prionopathy; a unique prion variant with inefficient transmission properties SO PRION LA English DT Meeting Abstract C1 [Diack, Abigail B.; Brown, Deborah; Boyle, Aileen; Morabito, Laura; Maclennan, David; Burgoyne, Paul; Piccardo, Pedro; Manson, Jean C.] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland. [Diack, Abigail B.; Brown, Deborah; Boyle, Aileen; Morabito, Laura; Maclennan, David; Burgoyne, Paul; Piccardo, Pedro; Manson, Jean C.] Univ Edinburgh, R D SVS, Edinburgh, Midlothian, Scotland. [Ritchie, Diane L.; Peden, Alexander H.; Ironside, James W.] Univ Edinburgh, Western Gen Hosp, Natl CJD Res & Surveillance Unit, Edinburgh, Midlothian, Scotland. [Piccardo, Pedro] US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA O.13 BP 17 EP 18 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900041 ER PT J AU Gregori, L Nag, N McDowell, K Carlson, CM Scheider, JR Heisey, DM Johnson, CJ Comoy, EE Deslys, JP Asher, DM AF Gregori, Luisa Nag, Nabanita McDowell, Kristy Carlson, Christina M. Scheider, Jay R. Heisey, Dennis M. Johnson, Christopher J. Comoy, Emmanuel E. Deslys, Jean-Philippe Asher, David M. TI In vitro amplification method to detect PrPTSE in blood of macaques infected with vCJD SO PRION LA English DT Meeting Abstract C1 [Gregori, Luisa; Nag, Nabanita; McDowell, Kristy; Asher, David M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Carlson, Christina M.; Scheider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.] US Geol Survey, Natl Wildlife Hlth Ctr, Madison, WI USA. [Carlson, Christina M.] Univ Wisconsin, Program Cellular & Mol Biol, Madison, WI 53706 USA. [Comoy, Emmanuel E.; Deslys, Jean-Philippe] CEA, Inst Emerging Dis & Innovat Therapies iMETI, Div Prions & Related Dis, Fontenay Aux Roses, France. RI Johnson, Christopher/B-1436-2009 OI Johnson, Christopher/0000-0003-4539-2581 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA O.25 BP 23 EP 24 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900053 ER PT J AU King, D Gill, AC Agarwal, S Piccardo, P Barron, RM AF King, Declan Gill, Andrew C. Agarwal, Sonya Piccardo, Pedro Barron, Rona M. TI Seeding PrP amyloid formation in the absence of TSE disease SO PRION LA English DT Meeting Abstract C1 [King, Declan; Gill, Andrew C.; Agarwal, Sonya; Barron, Rona M.] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat, Kensington, MD USA. RI Gill, Andrew/A-5219-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.06 BP 27 EP 27 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900061 ER PT J AU Piccardo, P Casalone, C Corona, C Chieppa, MN Favole, A Mazza, M Palmitessa, C Kurillova, LA Asher, DM AF Piccardo, Pedro Casalone, Cristina Corona, Cristiano Chieppa, Maria Novella Favole, Alessandra Mazza, Maria Palmitessa, Claudia Kurillova, Lubica A. Asher, David M. TI Cell substrates used to produce biologics failed to propagate the agent of atypical bovine spongiform encephalopathy (L-BSE) SO PRION LA English DT Meeting Abstract DE cell culture; biologics; prion; atypical BSE C1 [Piccardo, Pedro; Kurillova, Lubica A.; Asher, David M.] US FDA, Lab Bacterial & TSE Agents, Silver Spring, MD USA. [Casalone, Cristina; Corona, Cristiano; Chieppa, Maria Novella; Favole, Alessandra; Mazza, Maria; Palmitessa, Claudia] CEA, Ist Zooprofilatt Sperimentale Piemonte, Turin, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.125 BP 83 EP 84 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900180 ER PT J AU Cervenakova, L Sigurdson, CJ Piccardo, P Yakovleva, O Vasilyeva, I De Castro, J Saa, P Cervenak, A AF Cervenakova, Larisa Sigurdson, Christina J. Piccardo, Pedro Yakovleva, Oksana Vasilyeva, Irina De Castro, Jorge Saa, Paula Cervenak, Anton TI Successful transmission of chronic wasting disease (CWD) into mice over-expressing bovine prion protein (TgSB3985) SO PRION LA English DT Meeting Abstract DE chronic wasting disease; transmission; transgenic mouse; bovine prion protein C1 [Cervenakova, Larisa; Yakovleva, Oksana; Vasilyeva, Irina; De Castro, Jorge; Saa, Paula; Cervenak, Anton] Amer Red Cross, Holland Lab, Rockville, MD USA. [Sigurdson, Christina J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Piccardo, Pedro] US FDA, Lab TSE, OBRR, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.126 BP 84 EP 84 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900181 ER PT J AU Yakovleva, O Saa, P Piccardo, P de Castro, J Vasilyeva, I Cervenak, A Cervenakova, L AF Yakovleva, Oksana Saa, Paula Piccardo, Pedro de Castro, Jorge Vasilyeva, Irina Cervenak, Anton Cervenakova, Larisa TI Decoding differences in the replication of sporadic and variant Creutzfeldt-Jakob disease (CJD) in transgenic mice over-expressing human prion protein (TgRM) SO PRION LA English DT Meeting Abstract DE Sporadic Creutzfeldt-Jakob disease; variant Creutzfeldt-Jakob disease; blood infectivity; animal models C1 [Yakovleva, Oksana; Saa, Paula; de Castro, Jorge; Vasilyeva, Irina; Cervenak, Anton; Cervenakova, Larisa] Amer Natl Red Cross, Holland Lab, Rockville, MD USA. [Piccardo, Pedro] US FDA, LBTSEA, DETTD, OBRR,CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.220 BP 131 EP 131 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900275 ER PT J AU Yang, H Huang, Y Anderson, SA Gregori, L Asher, DM AF Yang, Hong Huang, Yin Anderson, Steven A. Gregori, Luisa Asher, David M. TI Dose-response for vCJD transmitted through blood transfusion SO PRION LA English DT Meeting Abstract C1 [Yang, Hong; Huang, Yin; Anderson, Steven A.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Gregori, Luisa; Asher, David M.] US FDA, Off Blood Evaluat & Res, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.228 BP 135 EP 135 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900283 ER PT J AU Chumakov, K AF Chumakov, Konstantin TI Polio Vaccines: The Past, Present and the Future SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 15th Annual International Meeting of the Institute-of-Human-Virology CY SEP 08-12, 2013 CL Moscow, RUSSIA SP Inst Human Virol, Univ Maryland Sch Med, Inst Human Virol C1 [Chumakov, Konstantin] US FDA, Off Vaccines Res & Review, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2014 VL 65 SU 2 MA 129 BP 53 EP 53 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3LD UT WOS:000339028300026 ER PT J AU Wear, KA AF Wear, Keith A. TI Time-domain separation of interfering waves in cancellous bone using bandlimited deconvolution: Simulation and phantom study SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID HUMAN TRABECULAR BONE; FREQUENCY-DEPENDENT ATTENUATION; BAYESIAN PROBABILITY-THEORY; 2 LONGITUDINAL-WAVES; SLOW WAVES; IN-VITRO; ULTRASOUND PROPAGATION; PHASE CANCELLATION; QUANTITATIVE ULTRASOUND; BACKSCATTER COEFFICIENT AB In through-transmission interrogation of cancellous bone, two longitudinal pulses ("fast" and "slow" waves) may be generated. Fast and slow wave properties convey information about material and micro-architectural characteristics of bone. However, these properties can be difficult to assess when fast and slow wave pulses overlap in time and frequency domains. In this paper, two methods are applied to decompose signals into fast and slow waves: bandlimited deconvolution and modified least-squares Prony's method with curve-fitting (MLSP broken vertical bar CF). The methods were tested in plastic and Zerdine (R) samples that provided fast and slow wave velocities commensurate with velocities for cancellous bone. Phase velocity estimates were accurate to within 6m/s (0.4%) (slow wave with both methods and fast wave with MLSP broken vertical bar CF) and 26 m/s (1.2%) (fast wave with bandlimited deconvolution). Midband signal loss estimates were accurate to within 0.2 dB (1.7%) (fast wave with both methods), and 1.0 dB (3.7%) (slow wave with both methods). Similar accuracies were found for simulations based on fast and slow wave parameter values published for cancellous bone. These methods provide sufficient accuracy and precision for many applications in cancellous bone such that experimental error is likely to be a greater limiting factor than estimation error. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Bldg 62,Room 3108,10903 New Hampshire Blvd, Silver Spring, MD 20993 USA. EM keith.wear@fda.hhs.gov FU FDA Office of Women's Health FX The author is grateful for funding from the FDA Office of Women's Health. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 74 TC 9 Z9 9 U1 1 U2 6 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2014 VL 135 IS 4 BP 2102 EP 2112 DI 10.1121/1.4868473 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA AK3EX UT WOS:000338307200049 PM 25235007 ER PT J AU Kim, DH AF Kim, Do-Hyun TI Consideration of dynamic photothermal effect for evaluation of scanning light sources in optical devices using pulsed source criteria SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE scanning medical device; optical radiation hazard; photothermal effect ID LASER AB Quantitative evaluation of the potential radiation hazards of scanning light sources in medical optical devices is critical. Currently, point scanning light sources of continuous radiation are treated as pulsed sources, where the dwell time at each point is equal to the pulse duration. This study compares the photothermal effects from scanning light and pulsed sources using numerical calculation for scanning without restricting aperture and with various spot sizes. The calculation results show that the thermal damage threshold of scanning source not restricted by measurement aperture does not significantly differ from that of pulsed source. Temporal temperature response and size-dependent photothermal effect also confirm the similarity between scanning and pulsed sources. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 US FDA, Silver Spring, MD 20993 USA. RP Kim, DH (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM do-hyun.kim@fda.hhs.gov FU Critical Path Initiative of US Food and Drug Administration [CP 21, CP 6] FX The author thanks Drs. Dexiu Shi, Jeeseong Hwang, Bruce Stuck, Robert Landry, and David Sliney for valuable discussions. This work was supported in part by Critical Path Initiative (CP 21 and CP 6) of US Food and Drug Administration. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 7 TC 0 Z9 0 U1 0 U2 1 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD APR PY 2014 VL 19 IS 4 AR 045004 DI 10.1117/1.JBO.19.4.045004 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AK3OO UT WOS:000338334300006 PM 24770659 ER PT J AU Zhang, J Jin, H Hu, J Yuan, Z Shi, W Ran, L Zhao, S Yang, X Meng, J Xu, X AF Zhang, J. Jin, H. Hu, J. Yuan, Z. Shi, W. Ran, L. Zhao, S. Yang, X. Meng, J. Xu, X. TI Serovars and antimicrobial resistance of non-typhoidal Salmonella from human patients in Shanghai, China, 2006-2010 SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Antimicrobial resistance; Salmonella; serovars ID ENTERICA SEROTYPE TYPHIMURIUM; LABORATORY-BASED SURVEILLANCE; ANTIBIOTIC-RESISTANCE; INFECTIONS; TRENDS; PHENOTYPES; BACTERIA; ANIMALS; TAIWAN; FRANCE AB We conducted a retrospective study on non-typhoidal Salmonella isolates from patients with diarrhoea in Shanghai, China, 2006-2010. A total of 1484 isolates of 70 Salmonella serovars were recovered from about 18 000 stool specimens. Serovars Enteritidis and Typhimurium were the most prevalent with isolation rates of 27.6% and 25.5%, respectively. The majority (1151, 77.6%) of the isolates were resistant to at least one antimicrobial, and 598 (40.3%) to more than three antimicrobials. Approximately half (50.9%) of the isolates were resistant to nalidixic acid and other resistance rates were sulfisoxazole (47.9%), streptomycin (37.6%), ampicillin (31.3%) and tetracycline (30.5%). Co-resistance to fluoroquinolones and the third- and fourth-generation cephalosporins was also identified. C1 [Zhang, J.; Yang, X.] Shanghai Jiao Tong Univ, Dept Food Sci & Technol, Sch Agr & Biol, Shanghai 200240, Peoples R China. [Jin, H.; Hu, J.; Yuan, Z.; Xu, X.] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China. [Shi, W.] Shanghai Municipal Ke Ma Jia Technol Ctr Microbio, Shanghai, Peoples R China. [Ran, L.] China Ctr Dis Control & Prevent, Beijing, Peoples R China. [Zhao, S.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. [Meng, J.] Univ Maryland, Dept Food Sci & Nutr, College Pk, MD 20742 USA. RP Zhang, J (reprint author), Shanghai Jiao Tong Univ, Dept Food Sci & Technol, Shanghai 200240, Peoples R China. EM junfeng-v@163.com; xbxu@scdc.sh.cn FU Mega-projects of Science and Technology Research of China [2012ZX10004215-003]; Subproject 6 of the Sino-US EID (Emerging Infectious Diseases) Cooperation Project; China Postdoctoral Science Foundation funded project [2012T50419, 2011M500781] FX This work was funded in part by Mega-projects of Science and Technology Research of China (No. 2012ZX10004215-003), the Subproject 6 of the Sino-US EID (Emerging Infectious Diseases) Cooperation Project and the China Postdoctoral Science Foundation funded project (Nos. 2012T50419, 2011M500781) NR 32 TC 11 Z9 12 U1 2 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 EI 1469-4409 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD APR PY 2014 VL 142 IS 4 BP 826 EP 832 DI 10.1017/S0950268813001659 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AJ5FY UT WOS:000337709300019 PM 23842508 ER PT J AU Jia, CX Alam, SK Azar, RZ Garra, B AF Jia, Congxian Alam, S. Kaisar Azar, Reza Zahiri Garra, Brian TI Estimation of Shear Modulus Ratio Between Inclusion and Background Using Strain Ratios in 2-D Ultrasound Elastography SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID CROSS-CORRELATION; SPECKLE TRACKING; BREAST-LESIONS; ELASTIC-MODULI; TISSUES; DIFFERENTIATION; PHANTOMS AB The goal of this study is to assess the effects of region of interest (ROI) selection and lesion size on estimates of shear modulus ratio from strain ratios to quantify relative stiffness of breast tumors. A theoretical model and finite element method (FEM) simulations of lesions with various shear modulus ratios are created for a 2-D plane strain deformation. Both the lesion and the surrounding tissue are assumed to be linearly elastic, isotropic, homogenous, and incompressible. The results from the model and simulations are in agreement that the lesion-to-surrounding shear modulus ratio is linearly proportional to the axial normal strain ratio for small lesions when the ROI in the surrounding tissue is at least four lesion diameters away from the lesion. For larger lesions, FEM simulations show that the estimated strain ratio using the same ROI location increases with the lesion size and would overestimate the shear modulus ratio. Therefore, a correction factor is necessary for large breast lesions when strain ratios are used to estimate the shear modulus ratio. We also demonstrate that strain elastograms calculated using a speckle tracking method on simulated RF data are accurate enough to observe the same effect on strain ratio estimation. This result is confirmed using experimental data acquired from two tissue-mimicking phantoms. Our findings will help clinicians to estimate strain ratios and shear modulus ratios more accurately for more reliable comparison of one clinical examination to another. C1 [Jia, Congxian; Garra, Brian] US FDA, Silver Spring, MD 20993 USA. [Alam, S. Kaisar] Rutgers State Univ, Piscataway, NJ USA. [Azar, Reza Zahiri] Ultrasonix Med Corp, Vancouver, BC, Canada. [Azar, Reza Zahiri] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Garra, Brian] Washington DC Vet Affairs Med Ctr, Washington, DC USA. RP Jia, CX (reprint author), US FDA, Silver Spring, MD 20993 USA. EM congxian.jia@fda.hhs.gov FU Susan G. Komen for the Cure [KG081601]; U.S. Department of Commerce [BS123456]; Center for Devices and Radiological Health (CDRH) FX This work was supported in part by the Susan G. Komen for the Cure grant KG081601 and the U.S. Department of Commerce under grant BS123456. This study was also supported in part by an appointment to the Research Participation Program at the Center for Devices and Radiological Health (CDRH) administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Food and Drug Administration (FDA). NR 31 TC 1 Z9 1 U1 3 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 EI 1525-8955 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD APR PY 2014 VL 61 IS 4 BP 611 EP 619 DI 10.1109/TUFFC.2014.2949 PG 9 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA AI8AW UT WOS:000337126100006 ER PT J AU Kuate, S Marino, MP Reiser, J AF Kuate, Seraphin Marino, Michael P. Reiser, Jakob TI Analysis of Partial Recombinants in Lentiviral Vector Preparations SO HUMAN GENE THERAPY METHODS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONDIVIDING CELLS; PACKAGING SYSTEM; COMPETENT; CONSTRUCTION; TRANSDUCTION; VIROTHERAPY; INTEGRATION; SAFETY AB The presence of replication-competent lentivirus (RCL) in lentiviral vector preparations is a major safety concern for clinical applications of such vectors. RCL are believed to emerge from rare recombinant vector genomes that are referred to as partial recombinants or Psi-Gag recombinants. To quantitatively determine the fraction of partial recombinants in lentiviral vector preparations and to analyze them at the DNA sequence level, we established a drug selection assay involving a lentiviral packaging construct containing a drug-resistance gene encoding blasticidin (BSD) resistance. Upon transduction of target cells, the BSD resistance gene confers BSD resistance to the transduced cells. The results obtained indicate that there were up to 156 BSD-resistant colonies in a total of 10(6) transducing vector particles. The predicted recombination events were verified by polymerase chain reaction using genomic DNA obtained from BSD-resistant cell clones and by DNA sequence analysis. In an attempt to reduce the emergence of partial recombinants, sequence overlaps between the packaging and the vector constructs were reduced by substituting the Rev response element (RRE) present in the vector construct using a heterologous RRE element derived from simian immunodeficiency virus (SIVmac(239)). The results obtained showed that a reduction of sequence overlaps resulted in an up to sevenfold reduction of the frequency of BSD-resistant colonies, indicating that the capacity to form partial recombinants was diminished. C1 [Kuate, Seraphin; Marino, Michael P.; Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Reiser, J (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 725, Rockville, MD 20852 USA. EM jakob.reiser@fda.hhs.gov NR 31 TC 0 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1946-6536 EI 1946-6544 J9 HUM GENE THER METHOD JI Hum. Gene Ther. Methods PD APR PY 2014 VL 25 IS 2 BP 126 EP 135 DI 10.1089/hgtb.2013.015 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI5MS UT WOS:000336912200004 PM 24367910 ER PT J AU Graham, DJ Zhou, EH McKean, S Levenson, M Calia, K Gelperin, K Ding, X MaCurdy, TE Worrall, C Kelman, JA AF Graham, David J. Zhou, Esther H. McKean, Stephen Levenson, Mark Calia, Katlyn Gelperin, Kate Ding, Xiao MaCurdy, Thomas E. Worrall, Chris Kelman, Jeffrey A. TI Cardiovascular and mortality risk in elderly Medicare beneficiaries treated with olmesartan versus other angiotensin receptor blockers SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE olmesartan; angiotensin receptor blockers (ARBs); cardiovascular; mortality; pharmacoepidemiology ID ACUTE MYOCARDIAL-INFARCTION; POSITIVE PREDICTIVE-VALUE; ADMINISTRATIVE DATA; CODING ACCURACY; MULTICENTER; DIAGNOSIS; STROKE; DEATH AB PurposeIn the randomized trial, Randomized Olmesartan and Diabetes Microalbuminuria Prevention, acute cardiovascular death was increased nearly fivefold in diabetic patients treated with high-dose olmesartan, an angiotensin receptor blocker (ARB), compared with placebo. MethodsMedicare beneficiaries were entered into new-user cohorts of olmesartan or other ARBs and followed on therapy for occurrence of acute myocardial infarction, stroke, or death. Analyses focused on specific subgroups defined by diabetes status, ARB dose, and duration of therapy. Hazard ratios (HR) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression, with other ARBs as reference. ResultsA total of 158054 olmesartan and 724673 other ARB users were followed for 54285 and 260390 person-years, respectively, during which 9237 endpoint events occurred. Lower-dose olmesartan was not associated with increased risk for any endpoint, regardless of duration of use. High-dose olmesartan for 6 months or longer was associated with increased risk of death in patients with diabetes (HR 2.03, 95%CI 1.09-3.75, p=0.02) and with reduced risk in nondiabetic patients (HR 0.46, 95%CI 0.24-0.86, p=0.01). Some, but not all, sensitivity analyses suggested that selective prescribing of olmesartan to healthier patients (channeling bias) may have accounted for the reduced risk in nondiabetic patients. ConclusionsHigh-dose olmesartan was associated with an increased risk of death in diabetic patients treated for 6 months or longer and with a reduced risk of death in nondiabetic patients, when compared with use of other ARBs. This latter effect was probably because of selective prescribing of olmesartan to healthier patients, although effect modification cannot be excluded. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. C1 [Graham, David J.; Zhou, Esther H.; Levenson, Mark; Gelperin, Kate; Ding, Xiao] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [McKean, Stephen; Calia, Katlyn; MaCurdy, Thomas E.] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas E.] Stanford Univ, Palo Alto, CA 94304 USA. [Worrall, Chris; Kelman, Jeffrey A.] Ctr Medicare & Medicaid Serv, Washington, DC USA. RP Graham, DJ (reprint author), US FDA, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22,Room 4314, Silver Spring, MD 20993 USA. EM david.graham1@fda.hhs.gov FU Centers for Medicare & Medicaid Services; Food and Drug Administration FX This study was funded through an intra-agency agreement between the Centers for Medicare & Medicaid Services and the Food and Drug Administration. NR 21 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2014 VL 23 IS 4 BP 331 EP 339 DI 10.1002/pds.3548 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AE1MB UT WOS:000333732300001 PM 24277678 ER PT J AU Zhou, EH Gelperin, K Levenson, MS Rose, M Hsueh, YH Graham, DJ AF Zhou, Esther H. Gelperin, Kate Levenson, Mark S. Rose, Martin Hsueh, Ya-Hui Graham, David J. TI Risk of acute myocardial infarction, stroke, or death in patients initiating olmesartan or other angiotensin receptor blockers a cohort study using the Clinical Practice Research Datalink SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE olmesartan; angiotensin receptor blockers (ARBs); acute myocardial infarction (AMI); death; pharmacoepidemiology ID OUTCOMES; BIAS AB PurposeResults of two randomized trials (ROADMAP and ORIENT) suggest that high-dose (40mg/day) olmesartan (Olm) is associated with increased cardiovascular mortality compared to placebo in diabetic patients. We evaluated the risks of acute myocardial infarction (AMI) and death in patients initiating Olm compared with an active comparator group, other angiotensin receptor blockers (ARBs), with a focus on high-dose and diabetic subgroups. MethodsWe conducted a cohort study with patients who initiated Olm or another ARB between 2003 and 2011, using the UK Clinical Practice Research Datalink GOLD. We included patients who had no prior ARB or angiotensin converting enzyme inhibitor exposure during the preceding 6 months. Hazard ratios (HRs) were estimated using Cox regression models with both multivariable adjustment and propensity score matching. ResultsThere were 3964 Olm and 54653 other-ARB initiators, respectively. Adjusted HRs comparing Olm and other-ARBs were 1.04 (95% CI: 0.75-1.42) for AMI and 1.16 (0.95-1.42) for death, using multivariable adjustment. Comparing patients initiated with a high-dose Olm and a high-dose other-ARB, HRs were 3.09 (0.94-10.13) for AMI and 2.03 (0.74-5.61) for death, using multivariable adjustment; and 4.38 (0.97-19.66) and 1.99 (0.63-6.32) for AMI and death, using propensity score matching. ConclusionsOverall, no differences in risk were observed in the main cohort analyses comparing Olm initiators with patients initiating therapy with other ARBs; however, HRs were marginally increased for all study endpoints which compared high-dose subgroups, suggesting potential increased risk may be associated with high-dose Olm. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. C1 [Zhou, Esther H.; Gelperin, Kate; Graham, David J.] US FDA, Off Surveillance & Epidemiol, Rockville, MD 20857 USA. [Levenson, Mark S.; Hsueh, Ya-Hui] US FDA, Off Biostat, Rockville, MD 20857 USA. [Rose, Martin] US FDA, Off New Drugs, Rockville, MD 20857 USA. RP Zhou, EH (reprint author), US FDA, Div Epidemiol 1, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM Esther.Zhou@fda.hhs.gov RI CPRD, CPRD/B-9594-2017 FU US Food and Drug Administration (FDA) FX Funding for this study came from the US Food and Drug Administration (FDA). NR 11 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2014 VL 23 IS 4 BP 340 EP 347 DI 10.1002/pds.3549 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AE1MB UT WOS:000333732300002 PM 24285502 ER PT J AU Sinha, VP Howey, DC Choi, SL Mace, KF Heise, T AF Sinha, V. P. Howey, D. C. Choi, S. L. Mace, K. F. Heise, T. TI Steady-state pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 dosed once-daily in patients with type 2 diabetes mellitus SO DIABETES OBESITY & METABOLISM LA English DT Article DE insulin analogues; pharmacodynamics; pharmacokinetics; type 2 diabetes ID NPH INSULIN; GLYCEMIC CONTROL; GLARGINE; DETEMIR; THERAPY; ANALOGS; TRIAL; LISPRO; VARIABILITY; CROSSOVER AB AimsTo assess the pharmacokinetics (PK) and glucodynamics (GD) of LY2605541 in patients with type 2 diabetes mellitus. MethodsThis parallel-group, open-label, dose-escalation study examined the PK and GD of basal insulin LY2605541 after single and multiple-dose administration. Fixed doses of LY2605541 (0.33-1.00U/kg) were given once-daily (QD) for 14days to insulin-treated patients with type 2 diabetes. A 24-h euglycaemic glucose clamp was conducted on days 1 and 14. ResultsPK steady state was achieved within 7-10days and the peak-to-trough fluctuation was <2, translating to a nearly peakless' glucose infusion rate at steady state and with a duration of action of at least 24h. Across dose levels t(1/2) ranged from 44.7 to 75.5h (2-3days). As steady state was achieved, there were dose-dependent reductions in the prandial insulin dose and in fasting blood glucose, which decreased to 60-100mg/dl across dose levels. Within-patient variability was <14 and <26% for the area under the concentration versus time curve (AUC) of the 8-point blood glucose profile and fasting blood glucose, respectively. The nocturnal glucose control between 03:00 and 09:00hours was relatively unchanged. Mild hypoglycaemia was the most common adverse event. ConclusionsIn this Phase I study of fixed LY2605541 doses without titration, LY2605541 was well-tolerated and demonstrated a flat PK and GD profile accompanied by glucose normalization, prandial insulin dose reduction and no severe hypoglycaemia. C1 [Sinha, V. P.; Howey, D. C.; Choi, S. L.; Mace, K. F.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Heise, T.] Profil, Neuss, Germany. RP Sinha, VP (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Vikram.Sinha@fda.hhs.gov FU Eli Lilly and Company FX The authors acknowledge the writing and editorial assistance of Stephanie Brillhart, inVentiv Health Clinical (Burlington, MA, USA). This study was funded by Eli Lilly and Company. Dr V. K. S. is the guarantor of this work and, as such, had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 20 TC 36 Z9 36 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD APR PY 2014 VL 16 IS 4 BP 344 EP 350 DI 10.1111/dom.12222 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8NE UT WOS:000332046500007 PM 24118909 ER PT J AU Chandrasekharaiah, M Kumar, DP Santosh, SS Palanivel, C Chigurupati, S Prasad, CS AF Chandrasekharaiah, M. Kumar, Prasanna D. Santosh, Sunil Singh Palanivel, C. Chigurupati, Srinu Prasad, C. S. TI Role of exogenous fibrolytic enzymes in ruminant feeding SO INDIAN JOURNAL OF ANIMAL SCIENCES LA English DT Review DE Biotechnology; Exogenous enzyme; Nutrition; Ruminants ID LACTATING DAIRY-COWS; IN-VITRO; TRICHODERMA-LONGIBRACHIATUM; RUMEN MICROORGANISMS; GROWTH-PERFORMANCE; EQUUS-BURCHELLI; MILK-PRODUCTION; FEEDLOT CATTLE; FECAL SAMPLES; DIETS AB The complex crop residues and straws are main feed resource available for feeding livestock in developing countries like India. These straws mainly consist of ligno-cellulose complex, which is not very easily and fully digested. Several attempts were tried to address the issue but met with varying degree of success. One of the approaches which holds promise is the use of exogenous fibrolytic enzyme in animals that are mainly fed on crop residue based diets. The major enzymes involved in cellulose hydrolysis are endocellulase (endoglucanase, endo-beta-1, 4-glucanase, carboxymethyl cellulase or beta-1, 4-glucan glucanohydrolase; E.C. 3.2.1.4), exocellulase (exoglucanase, exo-beta-1, 4-glucanase, cellulose beta-1, 4-cellobiosidase; E.C. 3.2.1.91), and B-glucosidase (cellobiase or glucohydrolase, E.C. 3.2.1.21). Many of these enzymes are being used worldwide in numerous industrial applications such as food industry in addition to animal feed industry. Use of the exogenous enzymes in cattle improved the digestibility of feeds, growth rate and milk production although results obtained were inconsistent. This review gives an insight into various exogenous fibrolytic enzymes involved in cell wall digestion, probable mode of action, and their level of inclusion as productivity enhancer in ruminant feeding. C1 [Chandrasekharaiah, M.; Kumar, Prasanna D.; Santosh, Sunil Singh; Palanivel, C.; Chigurupati, Srinu; Prasad, C. S.] Natl Inst Anim Nutr & Physiol, Bengaluru 560030, Karnataka, India. RP Chandrasekharaiah, M (reprint author), US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. EM chandrasekharaiah_m@yahoo.com; prsannaduvviri@gmail.com; digitalsunil@gmail.com; velstech@gmail.com; srinivasulu.chigurupati@fda.hhs.gov; directornianp@gmail.com NR 63 TC 0 Z9 0 U1 4 U2 19 PU INDIAN COUNC AGRICULTURAL RES PI NEW DELHI PA KAB-1, NEW DELHI 110012, INDIA SN 0367-8318 J9 INDIAN J ANIM SCI JI Indian J. Anim. Sci. PD APR PY 2014 VL 84 IS 4 BP 350 EP 356 PG 7 WC Agriculture, Dairy & Animal Science SC Agriculture GA AH0IR UT WOS:000335803100002 ER PT J AU Baek, JH Zhang, XY Williams, MC Schaer, DJ Buehler, PW D'Agnillo, F AF Baek, Jin Hyen Zhang, Xiaoyuan Williams, Matthew C. Schaer, Dominik J. Buehler, Paul W. D'Agnillo, Felice TI Extracellular Hb Enhances Cardiac Toxicity in Endotoxemic Guinea Pigs: Protective Role of Haptoglobin SO TOXINS LA English DT Article DE endothelium; endotoxin; hemoglobin; myocardial injury; haptoglobin ID INFLAMMATORY RESPONSE; OXIDATIVE STRESS; HEMOGLOBIN; SEPSIS; DYSFUNCTION; MORTALITY; ASSOCIATION; BIOMARKER; COMPLEX; MODEL AB Endotoxemia plays a major causative role in the myocardial injury and dysfunction associated with sepsis. Extracellular hemoglobin (Hb) has been shown to enhance the pathophysiology of endotoxemia. In the present study, we examined the myocardial pathophysiology in guinea pigs infused with lipopolysaccharide (LPS), a Gram-negative bacterial endotoxin, and purified Hb. We also examined whether the administration of the Hb scavenger haptoglobin (Hp) could protect against the effects observed. Here, we show that Hb infusion following LPS administration, but not either insult alone, increased myocardial iron deposition, heme oxygenase-1 expression, phagocyte activation and infiltration, as well as oxidative DNA damage and apoptosis assessed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunostaining, respectively. Co-administration of Hp significantly attenuated the myocardial events induced by the combination of LPS and Hb. These findings may have relevant therapeutic implications for the management of sepsis during concomitant disease or clinical interventions associated with the increased co-exposures to LPS and Hb, such as trauma, surgery or massive blood transfusions. C1 [Baek, Jin Hyen; Zhang, Xiaoyuan; Williams, Matthew C.; Buehler, Paul W.; D'Agnillo, Felice] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Schaer, Dominik J.] Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland. RP D'Agnillo, F (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM jin.baek@fda.hhs.gov; xiaoyuan.zhang@fda.hhs.gov; matthew.williams@fda.hhs.gov; dominik.schaer@usz.ch; paul.buehler@fda.hhs.gov; felice.dagnillo@fda.hhs.gov FU U.S. Department of Energy; U.S. Food and Drug Administration; FDA Modernizing Science Grants FX This project was supported in part by an appointment of Xiaoyuan Zhang to a Research Fellowship Program for the Center for Biologics Evaluation and Research, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration, and FDA Modernizing Science Grants awarded to Paul W. Buehler and Felice D'Agnillo. NR 37 TC 6 Z9 6 U1 0 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6651 J9 TOXINS JI Toxins PD APR PY 2014 VL 6 IS 4 BP 1244 EP 1259 DI 10.3390/toxins6041244 PG 16 WC Toxicology SC Toxicology GA AG9SO UT WOS:000335760200007 PM 24691127 ER PT J AU Sarkar, S Raymick, J Schmued, LC AF Sarkar, Sumit Raymick, James Schmued, Larry C. TI The Use of Recently Developed Histochemical Markers for Localizing Neurotoxicant Induced Regional Brain Pathologies SO TOXINS LA English DT Article DE Fluoro-Gold dextran; blood vessels; basement membrane; Fluoro-Gold (FG); amyloid A-beta; kainic acid; Fluoro-Ruby (FR); Amylo-Glo; AD; pericytes ID AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; NEUROVASCULAR MECHANISMS; PERICYTE MIGRATION; PARKINSONS-DISEASE; ENDOTHELIAL-CELLS; BLOOD-VESSELS; KAINIC ACID; BARRIER; DAMAGE AB Neuronal and vascular brain components are interrelated morphologically, physiologically and developmentally. Due to this close interrelationship, it is often difficult to understand the cause and effect relationship between neuronal vs. vascular dysfunction and pathology. This review will discuss four of the more promising recent developments for detecting vascular pathology, and will compare them with the labeling pattern seen with markers of glial and neuronal pathology; following exposure to well characterized neurotoxicants. To detect the vascular dysfunction in the brain, we recently developed a Fluoro-Turquoise gelatin conjugate (FT-gel), a fluorescent probe that helps to delineate between healthy vs. sclerotic vessels. Similarly, we have investigated the potential for Fluoro-Gold to label in vivo all the endothelial cells in the brain as they co-localize with RECA, an endothelial cell marker. We have also developed Amylo-Glo, a fluorescent tracer that can detect neurotoxic A-beta aggregates in the brain. In this article, we will discuss the potential use of these novel histochemical markers to study the neurotoxicant induced brain. We will also discuss neurovascular strategies that may offer novel therapeutic opportunities for neurodegenerative disorders. C1 [Sarkar, Sumit; Schmued, Larry C.] Natl Ctr Toxicol Res FDA, Div Neurotoxicol, Jefferson, AR 72079 USA. [Raymick, James] Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Sarkar, S (reprint author), Natl Ctr Toxicol Res FDA, Div Neurotoxicol, Jefferson, AR 72079 USA. EM Sumit.Sarkar@fda.hhs.gov; James.Raymick@fda.hhs.gov; Larry.Schmued@fda.hhs.gov FU National Center for Toxicological Research/FDA [E07312] FX This study was supported by the National Center for Toxicological Research/FDA (E07312). NR 54 TC 0 Z9 0 U1 1 U2 11 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6651 J9 TOXINS JI Toxins PD APR PY 2014 VL 6 IS 4 BP 1453 EP 1470 DI 10.3390/toxins6041453 PG 18 WC Toxicology SC Toxicology GA AG9SO UT WOS:000335760200021 PM 24763333 ER PT J AU Southwell, B Taylor, O Weger, S Weick-Brady, M Stifano, T Albersheim, H Fu, M Singh, S AF Southwell, Brian Taylor, Olivia Weger, Stacey Weick-Brady, Mary Stifano, Toni Albersheim, Harriet Fu, Maggie Singh, Simran TI GENERATIONAL DIFFERENCES IN OPENNESS TO WEB-BASED ABBREVIATED MEDICAL DEVICE LABELING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Southwell, Brian; Taylor, Olivia; Weger, Stacey] RTI Int, Res Triangle Pk, NC 27514 USA. [Weick-Brady, Mary; Stifano, Toni; Albersheim, Harriet; Fu, Maggie; Singh, Simran] US FDA, Silver Spring, MD USA. [Southwell, Brian] Univ N Carolina, Chapel Hill, NC USA. EM bsouthwell@rti.org NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S133 EP S133 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300512 ER PT J AU Ball, R AF Ball, Robert TI Perspectives on the future of postmarket vaccine safety surveillance and evaluation SO EXPERT REVIEW OF VACCINES LA English DT Article DE epidemiology; informatics; surveillance; pharmacovigilance; benefit-risk; vaccine safety; genomics ID GUILLAIN-BARRE-SYNDROME; EVENT REPORTING SYSTEM; 2009 MONOVALENT VACCINES; ADVERSE EVENTS; IMMUNIZATION-SAFETY; INFLUENZA VACCINES; PHARMACOVIGILANCE; INFORMATION; EFFICACY; DATALINK AB Strong, scientifically-based postmarket safety surveillance is critical to maintaining public confidence in vaccinations and reducing the burden from vaccine-preventable diseases. The infrastructure and scientific methods for postmarket safety surveillance have continuously improved over the last 30 years, with major enhancements in the last decade. Supporting and enhancing this system will continue to be important as the number of vaccines and people vaccinated expands globally. C1 US FDA, Off Biostat & Epidemiol, CBER, Rockville, MD 20857 USA. RP Ball, R (reprint author), US FDA, Off Biostat & Epidemiol, CBER, Rockville, MD 20857 USA. EM Robert.Ball@fda.hhs.gov NR 58 TC 1 Z9 1 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD APR PY 2014 VL 13 IS 4 BP 455 EP 462 DI 10.1586/14760584.2014.891941 PG 8 WC Immunology SC Immunology GA AG3QI UT WOS:000335334100004 PM 24606417 ER PT J AU Elahi, M Bambata, N Eshera, N Barr, H Howard, TB Scott, P Fadiran, E AF Elahi, Merina Bambata, Nkosazana Eshera, Noha Barr, Helen Howard, Tammie B. Scott, Pamela Fadiran, Emmanuel TI 20 Years of the Office of Women's Health: Health Impacts for Women from OWH-funded Research SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Elahi, Merina; Bambata, Nkosazana; Eshera, Noha; Barr, Helen; Howard, Tammie B.; Scott, Pamela; Fadiran, Emmanuel] US FDA, Off Womens Hlth, OC, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD APR 1 PY 2014 VL 23 IS 4 MA P121 BP 42 EP 42 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AE4EO UT WOS:000333934900122 ER PT J AU Pattaradilokrat, S Li, J Wu, J Qi, Y Eastman, RT Zilversmit, M Nair, SC Huaman, MC Quinones, M Jiang, H Li, N Zhu, J Zhao, K Kaneko, O Long, CA Su, XZ AF Pattaradilokrat, S. Li, J. Wu, J. Qi, Y. Eastman, R. T. Zilversmit, M. Nair, S. C. Huaman, M. C. Quinones, M. Jiang, H. Li, N. Zhu, J. Zhao, K. Kaneko, O. Long, C. A. Su, X-z TI Plasmodium genetic loci linked to host cytokine and chemokine responses SO GENES AND IMMUNITY LA English DT Article DE genetic mapping; cytokine; chemokine; inflammation; pathogenesis; virulence ID FALCIPARUM-INFECTED ERYTHROCYTES; INNATE IMMUNITY; MALARIA PARASITE; DUFFY ANTIGEN; TGF-BETA; YOELII; EXPRESSION; INVASION; SUSCEPTIBILITY; ACTIVATION AB Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1 beta, IP-10, IFN-gamma, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosomes 7 and 13 had significant (P<0.005) additive effects on IL-1 beta, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for a better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection. C1 [Pattaradilokrat, S.; Li, J.; Wu, J.; Qi, Y.; Eastman, R. T.; Zilversmit, M.; Nair, S. C.; Huaman, M. C.; Jiang, H.; Long, C. A.; Su, X-z] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20850 USA. [Pattaradilokrat, S.] Chulalongkorn Univ, Fac Sci, Dept Biol, Bangkok, Thailand. [Li, J.; Qi, Y.] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen, Fujian, Peoples R China. [Huaman, M. C.] Adv Biosci Labs, Rockville, MD USA. [Quinones, M.] NIAID, Bioinformat & Computat Biosci Branch, NIH, Rockville, MD 20850 USA. [Jiang, H.] US FDA, Silver Spring, MD USA. [Li, N.] MedImmune, Gaithersburg, MD USA. [Zhu, J.] NIH, Genet & Dev Biol Ctr, Bethesda, MD 20892 USA. [Zhao, K.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Kaneko, O.] Nagasaki Univ, Inst Trop Med, Dept Protozool, Nagasaki 852, Japan. [Kaneko, O.] Nagasaki Univ, Global Ctr Excellence Program, Nagasaki 852, Japan. RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3E-24B,12735 Twinbrook Pkwy, Rockville, MD 20850 USA. EM xsu@niaid.nih.gov RI Wu, Jian/K-2038-2015; OI Wu, Jian/0000-0001-8011-9551; Su, Xinzhuan/0000-0003-3246-3248 FU Intramural Research Program of the Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Project 111; State Bureau of Foreign Experts; Ministry of Education of China [B06016]; National Natural Science Foundation of China [81271858, 81201324, 81220108019] FX We thank Drs Alan Sher and David Sacks for valuable advice and comments and Brenda Rae Marshall, DPSS, NIAID, for editing. This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and partially by 'Project 111' sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (B06016) and by the National Natural Science Foundation of China (#81271858, #81201324 and #81220108019). NR 58 TC 7 Z9 7 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD APR-MAY PY 2014 VL 15 IS 3 BP 145 EP 152 DI 10.1038/gene.2013.74 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA AF8QT UT WOS:000334981400002 PM 24452266 ER PT J AU Hilmer, SN Gnjidic, D Abernethy, DR AF Hilmer, Sarah N. Gnjidic, Danijela Abernethy, Darrell R. TI Drug Burden Index for International Assessment of the Functional Burden of Medications in Older People SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID PHYSICAL FUNCTION C1 [Hilmer, Sarah N.; Gnjidic, Danijela] Univ Sydney, Royal N Shore Hosp, Sydney Med Sch, Dept Clin Pharmacol & Aged Care, Sydney, NSW 2006, Australia. [Hilmer, Sarah N.; Gnjidic, Danijela] Kolling Inst Med Res, Sydney, NSW, Australia. [Gnjidic, Danijela] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia. [Abernethy, Darrell R.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Abernethy, Darrell R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Hilmer, SN (reprint author), Univ Sydney, Royal N Shore Hosp, Sydney Med Sch, Dept Clin Pharmacol & Aged Care, Sydney, NSW 2006, Australia. OI Hilmer, Sarah/0000-0002-5970-1501 NR 8 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2014 VL 62 IS 4 BP 791 EP 792 DI 10.1111/jgs.12707 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AE8YV UT WOS:000334289900040 PM 24731040 ER PT J AU Mahmood, I Boxenbaum, H AF Mahmood, Iftekhar Boxenbaum, Harold TI Vertical allometry: Fact or fiction? SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Vertical allometry; Allometric scaling; Clearance; Volume of distribution ID HUMAN DRUG CLEARANCE; ALPHA(1)-ACID GLYCOPROTEIN; PROTEIN-BINDING; ALPHA-1-ACID GLYCOPROTEIN; CLINICAL-PHARMACOLOGY; PHARMACOKINETICS; PREDICTION; WARFARIN; HUMANS; UCN-01 AB In pharmacokinetics, vertical allometry is referred to the clearance of a drug when the predicted human clearance is substantially higher than the observed human clearance. Vertical allometry was initially reported for diazepam based on a 33-fold higher human predicted clearance than the observed human clearance. In recent years, it has been found that many other drugs besides diazepam, can be classified as drugs which exhibit vertical allometry. Over the years, many questions regarding vertical allometry have been raised. For example, (1) How to define and identify the vertical allometry? (2) How much difference should be between predicted and observed human clearance values before a drug could be declared 'a drug which follows vertical allometry'? (3) If somehow one can identify vertical allometry from animal data, how this information can be used for reasonably accurate prediction of clearance in humans? This report attempts to answer the aforementioned questions. The concept of vertical allometry at this time remains complex and obscure but with more extensive works one can have better understanding of 'vertical allometry'. Published by Elsevier Inc. C1 [Mahmood, Iftekhar; Boxenbaum, Harold] US FDA, Off Blood Review & Res, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), US FDA, Off Blood Review & Res, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20857 USA. EM Iftekhar.mahmood@fda.hhs.gov NR 29 TC 4 Z9 4 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 EI 1096-0295 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 2014 VL 68 IS 3 BP 468 EP 474 DI 10.1016/j.yrtph.2014.02.005 PG 7 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA AE6YY UT WOS:000334145100017 PM 24534003 ER PT J AU Nadler, Z Wang, B Wollstein, G Nevins, JE Ishikawa, H Bilonick, R Kagemann, L Sigal, IA Ferguson, RD Patel, A Hammer, DX Schuman, JS AF Nadler, Zach Wang, Bo Wollstein, Gadi Nevins, Jessica E. Ishikawa, Hiroshi Bilonick, Richard Kagemann, Larry Sigal, Ian A. Ferguson, R. Daniel Patel, Ankit Hammer, Daniel X. Schuman, Joel S. TI Repeatability of in vivo 3D lamina cribrosa microarchitecture using adaptive optics spectral domain optical coherence tomography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID NERVE-FIBER-LAYER; SCANNING LASER OPHTHALMOSCOPY; GLAUCOMATOUS EYES; IMAGE-ANALYSIS; REPRODUCIBILITY; AGREEMENT; DEFECTS; HEALTHY; DAMAGE; PORES AB We demonstrate the repeatability of lamina cribrosa (LC) microarchitecture for in vivo 3D optical coherence tomography (OCT) scans of healthy, glaucoma suspects, and glaucomatous eyes. Eyes underwent two scans using a prototype adaptive optics spectral domain OCT (AO-SDOCT) device from which LC microarchitecture was semi-automatically segmented. LC segmentations were used to quantify pore and beam structure through several global microarchitecture parameters. Repeatability of LC microarchitecture was assessed qualitatively and quantitatively by calculating parameter imprecision. For all but one parameters (pore volume) measurement imprecision was <4.7% of the mean value, indicating good measurement reproducibility. Imprecision ranged between 27.3% and 54.5% of the population standard deviation for each parameter, while there was not a significant effect on imprecision due to disease status, indicating utility in testing for LC structural trends. (C) 2014 Optical Society of America C1 [Nadler, Zach; Wang, Bo; Wollstein, Gadi; Nevins, Jessica E.; Ishikawa, Hiroshi; Bilonick, Richard; Kagemann, Larry; Sigal, Ian A.; Schuman, Joel S.] Univ Pittsburgh, Sch Med, Inst Eye & Ear, UPMC Eye Ctr,Ophthalmol & Visual Sci Res Ctr, Pittsburgh, PA 15260 USA. [Wang, Bo; Ishikawa, Hiroshi; Bilonick, Richard; Kagemann, Larry; Sigal, Ian A.; Schuman, Joel S.] Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA USA. [Ferguson, R. Daniel; Patel, Ankit] Phys Sci Inc, Andover, MA 01810 USA. [Hammer, Daniel X.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Nadler, Z (reprint author), Univ Pittsburgh, Sch Med, Inst Eye & Ear, UPMC Eye Ctr,Ophthalmol & Visual Sci Res Ctr, Pittsburgh, PA 15260 USA. EM wollsteing@upmc.edu OI Kagemann, Larry/0000-0001-8961-0187; Ishikawa, Hiroshi/0000-0001-6310-5748 FU NIH [R01-EY013178, R44-EY018986, P30-EY008098]; Eye and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness (New York, NY) FX The authors acknowledge this work would not have been possible without funding and support from: NIH R01-EY013178, R44-EY018986, P30-EY008098; Eye and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness (New York, NY). NR 39 TC 12 Z9 13 U1 0 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD APR 1 PY 2014 VL 5 IS 4 BP 1114 EP 1123 DI 10.1364/BOE.5.001114 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AE6DB UT WOS:000334078100011 PM 24761293 ER PT J AU Jackson, LS AF Jackson, Lauren S. TI Toxicology and Chemical Food Safety in the Journal of Food Science: 1936-the present SO JOURNAL OF FOOD SCIENCE LA English DT Editorial Material C1 US FDA, Inst Food Safety & Hlth, Rockville, MD 20857 USA. RP Jackson, LS (reprint author), US FDA, Inst Food Safety & Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 2 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1147 EI 1750-3841 J9 J FOOD SCI JI J. Food Sci. PD APR PY 2014 VL 79 IS 4 BP IV EP V DI 10.1111/1750-3841.12452 PG 2 WC Food Science & Technology SC Food Science & Technology GA AE3OO UT WOS:000333886000044 PM 24712494 ER PT J AU Mitkus, RJ King, DB Walderhaug, MO Forshee, RA AF Mitkus, Robert J. King, David B. Walderhaug, Mark O. Forshee, Richard A. TI A Comparative Pharmacokinetic Estimate of Mercury in U.S. Infants Following Yearly Exposures to Inactivated Influenza Vaccines Containing Thimerosal SO RISK ANALYSIS LA English DT Article DE safety; MeHg; pharmacokinetics; modeling; thimerosal ID NEUROPSYCHOLOGICAL OUTCOMES; QUALITATIVE EVALUATION; METHYL MERCURY; NEONATAL MICE; METHYLMERCURY; EXTRAPOLATION; METABOLISM; BRAIN; RISK; RAT AB The use of thimerosal preservative in childhood vaccines has been largely eliminated over the past decade in the United States because vaccines have been reformulated in single-dose vials that do not require preservative. An exception is the inactivated influenza vaccines, which are formulated in both multidose vials requiring preservative and preservative-free single-dose vials. As part of an ongoing evaluation by USFDA of the safety of biologics throughout their lifecycle, the infant body burden of mercury following scheduled exposures to thimerosal preservative in inactivated influenza vaccines in the United States was estimated and compared to the infant body burden of mercury following daily exposures to dietary methylmercury at the reference dose established by the USEPA. Body burdens were estimated using kinetic parameters derived from experiments conducted in infant monkeys that were exposed episodically to thimerosal or MeHg at identical doses. We found that the body burden of mercury (AUC) in infants (including low birth weight) over the first 4.5 years of life following yearly exposures to thimerosal was two orders of magnitude lower than that estimated for exposures to the lowest regulatory threshold for MeHg over the same time period. In addition, peak body burdens of mercury following episodic exposures to thimerosal in this worst-case analysis did not exceed the corresponding safe body burden of mercury from methylmercury at any time, even for low-birth-weight infants. Our pharmacokinetic analysis supports the acknowledged safety of thimerosal when used as a preservative at current levels in certain multidose infant vaccines in the United States. C1 [Mitkus, Robert J.; King, David B.; Walderhaug, Mark O.; Forshee, Richard A.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mitkus, RJ (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 210, Rockville, MD 20852 USA. EM robert.mitkus@fda.hhs.gov NR 51 TC 2 Z9 3 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 EI 1539-6924 J9 RISK ANAL JI Risk Anal. PD APR PY 2014 VL 34 IS 4 BP 735 EP 750 DI 10.1111/risa.12124 PG 16 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA AE4JN UT WOS:000333948800011 PM 24117921 ER PT J AU Alayash, AI AF Alayash, Abdu I. TI Blood substitutes: why haven't we been more successful? SO TRENDS IN BIOTECHNOLOGY LA English DT Review DE Blood substitutes; Hemoglobin; Heme; Oxidative toxicity ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; OXYGEN CARRIERS; POLYETHYLENE-GLYCOL; NITRIC-OXIDE; EXTRACELLULAR HEMOGLOBIN; EXCHANGE-TRANSFUSION; CLINICAL DEVELOPMENT; HEMORRHAGIC-SHOCK; OXIDATIVE STRESS AB Persistent safety concerns have stalled the development of viable hemoglobin (Hb)-based oxygen carriers (HBOCs). HBOCs have several advantages over human blood, including availability, long-term storage, and lack of infectious risk. The basis of HBOC toxicity is poorly understood, however, several mechanisms have been suggested, including Hb extravasation across the blood vessel wall, scavenging of endothelial nitric oxide (NO), oversupply of oxygen, and heme-mediated oxidative side reactions. Although there are some in vitro and limited animal studies supporting these mechanisms, heme-mediated reactivity appears to provide an alternative path that can explain some of the observed pathophysiological changes. Moreover, recent mechanistic and animal studies support a role for globin and heme scavengers in controlling oxidative toxicity associated with Hb infusion. C1 US FDA, Lab Biochem & Vasc Biol, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov FU National Institutes of Health (NIH) [HL110900]; U.S. Food and Drug Administration (MODSCI) FX The author wishes to acknowledge the contribution of past and present members of the Laboratory of Biochemistry and Vascular Biology (LBVB) to this work. This work was supported by National Institutes of Health (NIH) grant HL110900, and the U.S. Food and Drug Administration (MODSCI) NR 52 TC 31 Z9 31 U1 6 U2 44 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD APR PY 2014 VL 32 IS 4 BP 177 EP 185 DI 10.1016/j.tibtech.2014.02.006 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AE6UD UT WOS:000334132500004 PM 24630491 ER PT J AU Fix, BV O'Connor, RJ Vogl, L Smith, D Bansal-Travers, M Conway, KP Ambrose, B Yang, L Hyland, A AF Fix, Brian V. O'Connor, Richard J. Vogl, Lisa Smith, Danielle Bansal-Travers, Maansi Conway, Kevin P. Ambrose, Bridget Yang, Ling Hyland, Andrew TI Patterns and correlates of polytobacco use in the United States over a decade: NSDUH 2002-2011 SO ADDICTIVE BEHAVIORS LA English DT Article DE Polytobacco use; Tobacco; Cigarettes; Smokeless tobacco; Cigars; Tobacco use trends ID SMOKELESS TOBACCO; CIGARETTE-SMOKING; MALE-ADOLESCENTS; YOUNG-ADULTS; PRODUCTS; SMOKERS; SNUS; POPULATION; PREVALENCE; ALCOHOL AB Background: Few studies have examined the patterns and correlates of polytobacco use among a large, nationally representative population over an extended period of time. Methods: This study examined 10 years of data from the National Survey on Drug Use and Health (NSDUH) to establish time trends and correlates for exclusive and mixed use of cigarettes, smokeless tobacco (SLT), cigars, and pipes. Results: Results show that rates of polytobacco use were essentially unchanged from 2002 to 2011 (8.7% to 7.4%), though some product combinations, including cigarettes and SLT, cigars and SLT, and use of more than two products have increased. In tobacco users under age 26, the proportion of polytobacco use increased, even as overall tobacco use declined. The factors associated with polytobacco use among tobacco users included sex, income, education, risk taking/seeking behaviors, and outward indicators of 'risk-liability'. Conclusions: Findings provide a snapshot of trends of single and polytobacco product use as well as trends in combinations of product use. Longitudinal studies are needed to examine the sequence of individual patterns of tobacco product use and to identify whether polytobacco use results in greater nicotine dependence, increased exposure to harmful and potentially harmful constituents and/or greater risk of tobacco related disease. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Fix, Brian V.; O'Connor, Richard J.; Vogl, Lisa; Smith, Danielle; Bansal-Travers, Maansi; Hyland, Andrew] Roswell Pk Canc Inst, Dept Hlth Behav, Buffalo, NY 14263 USA. [Conway, Kevin P.] NIDA, NIH, Bethesda, MD 20892 USA. [Ambrose, Bridget; Yang, Ling] US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. RP Fix, BV (reprint author), Roswell Pk Canc Inst, Dept Hlth Behav, Elm & Carlton St, Buffalo, NY 14263 USA. EM brian.fix@roswellpark.org RI O'Connor, Richard/A-6961-2009; OI Conway, Kevin/0000-0002-7638-339X FU National Institute on Drug Abuse; National Institutes of Health; Food and Drug Administration; Department of Health and Human Services [HHSN271201100027C] FX This project has been funded in whole or in part with Federal funds from the National Institute on Drug Abuse, the National Institutes of Health, and the Food and Drug Administration, the Department of Health and Human Services, under Contract No. HHSN271201100027C. Funders had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 30 TC 21 Z9 21 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD APR PY 2014 VL 39 IS 4 BP 768 EP 781 DI 10.1016/j.addbeh.2013.12.015 PG 14 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AD8JF UT WOS:000333511600004 PM 24457900 ER PT J AU Jones, HE Deppen, K Hudak, ML Leffert, L McClelland, C Sahin, L Starer, J Terplan, M Thorp, JM Walsh, J Creanga, AA AF Jones, Hendree E. Deppen, Krisanna Hudak, Mark L. Leffert, Lisa McClelland, Carol Sahin, Leyla Starer, Jacquelyn Terplan, Mishka Thorp, John M., Jr. Walsh, James Creanga, Andreea A. TI Clinical care for opioid-using pregnant and postpartum women: the role of obstetric providers SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE opioid-agonist; opioid use; substance use ID NEONATAL ABSTINENCE SYNDROME; OPIATE WITHDRAWAL; ALCOHOL-USE; METHADONE; BUPRENORPHINE; OUTCOMES; EMPATHY; ISSUES AB We review clinical care issues that are related to illicit and therapeutic opioid use among pregnant women and women in the postpartum period and outline the major responsibilities of obstetrics providers who care for these patients during the antepartum, intrapartum, and postpartum periods. Selected patient treatment issues are highlighted, and case examples are provided. Securing a strong rapport and trust with these patients is crucial for success in delivering high-quality obstetric care and in coordinating services with other specialists as needed. Obstetrics providers have an ethical obligation to screen, assess, and provide brief interventions and referral to specialized treatment for patients with drug use disorders. Opioid-dependent pregnant women often can be treated effectively with methadone or buprenorphine. These medications are classified as pregnancy category C medications by the Food and Drug Administration, and their use in the treatment of opioid-dependent pregnant patients should not be considered "off-label." Except in rare special circumstances, medication-assisted withdrawal during pregnancy should be discouraged because of a high relapse rate. Acute pain management in this population deserves special consideration because patients who use opioids can be hypersensitive to pain and because the use of mixed opioid-agonist/antagonists can precipitate opioid withdrawal. In the absence of other indications, pregnant women who use opioids do not require more intense medical care than other pregnant patients to ensure adequate treatment and the best possible outcomes. Together with specialists in pain and addiction medicine, obstetricians can coordinate comprehensive care for pregnant women who use opioids and women who use opioids in the postpartum period. C1 [Jones, Hendree E.; McClelland, Carol; Thorp, John M., Jr.] Univ North Carolina Chapel Hill, UNC Sch Med, Dept Obstet & Gynecol, UNC Horizons Program, Carrboro, NC USA. [Deppen, Krisanna] Grant Med Ctr, Dept Family Med, Columbus, OH USA. [Hudak, Mark L.] Univ Florida, Coll Med Jacksonville, Dept Pediat, Gainesville, FL 32611 USA. [Leffert, Lisa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Sahin, Leyla] US FDA, Maternal Hlth Team, Off New Drugs, Silver Spring, MD USA. [Starer, Jacquelyn] Brigham & Womens Faulkner Hosp, Addict Recovery Program, Boston, MA USA. [Terplan, Mishka] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Dept Obstet Gynecol & Reprod Sci, Baltimore, MD 21201 USA. [Walsh, James] Swedish Med Ctr, Addict Recovery Serv, Seattle, WA USA. [Creanga, Andreea A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. RP Jones, HE (reprint author), UNC Horizons, 400 Roberson St, Carrboro, NC 27510 USA. EM hendree_jones@med.unc.edu NR 46 TC 17 Z9 17 U1 0 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2014 VL 210 IS 4 BP 302 EP 310 DI 10.1016/j.ajog.2013.10.010 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AD6WM UT WOS:000333401900003 PM 24120973 ER PT J AU Balter, S Miller, DL AF Balter, Stephen Miller, Donald L. TI Patient Skin Reactions From Interventional Fluoroscopy Procedures SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE fluoroscopy; interventional radiology; radiation effects; skin injury ID RADIATION SAFETY PROGRAM; RADIOLOGY PROCEDURES; GUIDED PROCEDURES; INJURIES; MANAGEMENT; GUIDELINES AB OBJECTIVE. This article presents relevant physics, technology, and radiobiology along with a summary of operational guidelines for radiation management in interventional fluoroscopy procedures. CONCLUSION. Fluoroscopically guided interventional procedures offer patients clinical and economic benefits as compared with the alternatives. Radiation- induced skin injuries are uncommon but continue to occur. C1 [Balter, Stephen] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Balter, S (reprint author), Columbia Univ, Med Ctr, 173 Ft Washington Ave,HC 2-605, New York, NY 10032 USA. EM sb2455@columbia.edu NR 30 TC 14 Z9 15 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2014 VL 202 IS 4 BP W335 EP W342 DI 10.2214/AJR.13.12029 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD7OU UT WOS:000333454300003 PM 24660731 ER PT J AU Wang, F Yang, QR Qu, YZ Meng, JH Ge, BL AF Wang, Fei Yang, Qianru Qu, Yinzhi Meng, Jianghong Ge, Beilei TI Evaluation of a Loop-Mediated Isothermal Amplification Suite for the Rapid, Reliable, and Robust Detection of Shiga Toxin-Producing Escherichia coli in Produce SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID IN-GROUND BEEF; ACTIVE SURVEILLANCE NETWORK; 10 US SITES; LISTERIA-MONOCYTOGENES; UNITED-STATES; PCR DETECTION; O157 STRAINS; FOOD; TIME; ASSAYS AB Shiga toxin-producing Escherichia coli (STEC) strains are a leading cause of produce-associated outbreaks in the United States. Rapid, reliable, and robust detection methods are needed to better ensure produce safety. We recently developed a loop-mediated isothermal amplification (LAMP) suite for STEC detection. In this study, the STEC LAMP suite was comprehensively evaluated against real-time quantitative PCR (qPCR) using a large panel of bacterial strains (n = 156) and various produce items (several varieties of lettuce, spinach, and sprouts). To simulate real-world contamination events, produce samples were surface inoculated with a low level (1.2 to 1.8 CFU/25 g) of individual STEC strains belonging to seven serogroups (O26, O45, O103, O111, O121, O145, and O157) and held at 4 C for 48 h before testing. Six DNA extraction methods were also compared using produce enrichment broths. All STEC targets and their subtypes were accurately detected by the LAMP suite. The detection limits were 1 to 20 cells per reaction in pure culture and 10(5) to 10(6) CFU per 25 g (i.e., 10(3) to 10(4) CFU per g) in produce, except for strains harboring the stx(2c), eae-beta, and eae-theta subtypes. After 6 to 8 h of enrichment, the LAMP suite achieved accurate detection of low levels of STEC strains of various stx(2) and eae subtypes in lettuce and spinach varieties but not in sprouts. A similar trend of detection was observed for qPCR. The PrepMan Ultra sample preparation reagent yielded the best results among the six DNA extraction methods. This research provided a rapid, reliable, and robust method for detecting STEC in produce during routine sampling and testing. The challenge with sprouts detection by both LAMP and qPCR calls for special attention to further analysis. C1 [Wang, Fei; Yang, Qianru; Ge, Beilei] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. [Wang, Fei; Qu, Yinzhi; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Yang, Qianru] Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA. RP Ge, BL (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. EM beilei.ge@fda.hhs.gov RI Wang, Fei/J-4353-2014 FU Center for Produce Safety at the University of California, Davis [SCB11064] FX This work was supported in part by a research grant (SCB11064) from the Center for Produce Safety at the University of California, Davis. NR 52 TC 6 Z9 8 U1 0 U2 29 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 2014 VL 80 IS 8 BP 2516 EP 2525 DI 10.1128/AEM.04203-13 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA AD8QV UT WOS:000333531600021 PM 24509927 ER PT J AU Feinen, B Petrovsky, N Verma, A Merkel, TJ AF Feinen, Brandon Petrovsky, Nikolai Verma, Anita Merkel, Tod J. TI Advax-Adjuvanted Recombinant Protective Antigen Provides Protection against Inhalational Anthrax That Is Further Enhanced by Addition of Murabutide Adjuvant SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID SYNTHETIC IMMUNOMODULATOR MURABUTIDE; AEROSOL CHALLENGE MODEL; BACILLUS-ANTHRACIS; DENDRITIC CELLS; DELTA INULIN; POLYSACCHARIDE ADJUVANT; NEUTRALIZING ANTIBODY; MURINE MACROPHAGES; NASAL IMMUNIZATION; INFLUENZA VACCINE AB Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by similar to 4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy. C1 [Feinen, Brandon; Verma, Anita; Merkel, Tod J.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Petrovsky, Nikolai] Flinders Med Ctr, Bedford Pk, SA, Australia. [Petrovsky, Nikolai] Vaxine Pty Ltd, Bedford Pk, SA, Australia. RP Merkel, TJ (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM tod.merkel@fda.hhs.gov OI Petrovsky, Nikolai/0000-0002-1580-5245 FU internal FDA funds; National Institutes of Health (NIH) [U01AI061142, HHSN272200800039C] FX This work was supported by internal FDA funds provided to support the research program of T.J.M. The funding agency had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. The development of Advax adjuvant was supported by contracts U01AI061142 and HHSN272200800039C from the National Institutes of Health (NIH). NR 60 TC 18 Z9 18 U1 3 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD APR PY 2014 VL 21 IS 4 BP 580 EP 586 DI 10.1128/CVI.00019-14 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AE0TG UT WOS:000333678500016 PM 24554695 ER PT J AU Lindblad, AS Manukyan, Z Purohit-Sheth, T Gensler, G Okwesili, P Meeker-O'Connell, A Ball, L Marler, JR AF Lindblad, Anne S. Manukyan, Zorayr Purohit-Sheth, Tejashri Gensler, Gary Okwesili, Paul Meeker-O'Connell, Ann Ball, Leslie Marler, John R. TI Central site monitoring: Results from a test of accuracy in identifying trials and sites failing Food and Drug Administration inspection SO CLINICAL TRIALS LA English DT Article ID CLINICAL-TRIALS; FRAUD; COSTS AB Background Site monitoring and source document verification account for 15%-30% of clinical trial costs. An alternative is to streamline site monitoring to focus on correcting trial-specific risks identified by central data monitoring. This risk-based approach could preserve or even improve the quality of clinical trial data and human subject protection compared to site monitoring focused primarily on source document verification. Purpose To determine whether a central review by statisticians using data submitted to the Food and Drug Administration (FDA) by clinical trial sponsors can identify problem sites and trials that failed FDA site inspections. Methods An independent Analysis Center (AC) analyzed data from four anonymous new drug applications (NDAs) where FDA had performed site inspections overseen by FDA's Office of Scientific Investigations (OSI). FDA team members in the OSI chose the four NDAs from among all NDAs with data in Study Data Tabulation Model (SDTM) format. Two of the NDAs had data that OSI had deemed unreliable in support of the application after FDA site inspections identified serious data integrity problems. The other two NDAs had clinical data that OSI deemed reliable after site inspections. At the outset, the AC knew only that the experimental design specified two NDAs with significant problems. FDA gave the AC no information about which NDAs had problems, how many sites were inspected, or how many were found to have problems until after the AC analysis was complete. The AC evaluated randomization balance, enrollment patterns, study visit scheduling, variability of reported data, and last digit reference. The AC classified sites as 'High Concern', 'Moderate Concern', 'Mild Concern', or 'No Concern'. Results The AC correctly identified the two NDAs with data deemed unreliable by OSI. In addition, central data analysis correctly identified 5 of 6 (83%) sites for which FDA recommended rejection of data and 13 of 15 sites (87%) for which any regulatory deviations were identified during inspection. Of the six sites for which OSI reviewed inspections and found no deviations, the central process flagged four at the lowest level of concern, one at a moderate level, and one was not flagged. Limitations Central data monitoring during the conduct of a trial while data checking was in progress was not evaluated. Conclusion Systematic central monitoring of clinical trial data can identify problems at the same trials and sites identified during FDA site inspections. Central data monitoring in conjunction with an overall monitoring process that adapts to identify risks as a trial progresses has the potential to reduce the frequency of site visits while increasing data integrity and decreasing trial costs compared to processes that are dependent primarily on source documentation. C1 [Lindblad, Anne S.; Manukyan, Zorayr; Gensler, Gary] EMMES Corp, Rockville, MD USA. [Purohit-Sheth, Tejashri; Okwesili, Paul; Meeker-O'Connell, Ann; Ball, Leslie; Marler, John R.] US FDA, Silver Spring, MD 20993 USA. RP Marler, JR (reprint author), US FDA, Div Neurol Prod, 10903 New Hampshire Ave,Bldg 22 Room 4340, Silver Spring, MD 20993 USA. EM john.marler@fda.hhs.gov FU FDA Center for Drug Evaluation and Research (CDER) through its Regulatory Science and Review (RSR) Enhancement Committee FX This collaboration was supported in part by a grant from The FDA Center for Drug Evaluation and Research (CDER) through its Regulatory Science and Review (RSR) Enhancement Committee to John Marler in the CDER Office of New Drugs, Division of Neurological Products. NR 17 TC 11 Z9 11 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2014 VL 11 IS 2 BP 205 EP 217 DI 10.1177/1740774513508028 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AE0HT UT WOS:000333645300008 PM 24296321 ER PT J AU Zhang, J Carlin, BP Neaton, JD Soon, GG Nie, L Kane, R Virnig, BA Chu, HT AF Zhang, Jing Carlin, Bradley P. Neaton, James D. Soon, Guoxing G. Nie, Lei Kane, Robert Virnig, Beth A. Chu, Haitao TI Network meta-analysis of randomized clinical trials: Reporting the proper summaries SO CLINICAL TRIALS LA English DT Article ID MIXED TREATMENT COMPARISONS; ODDS RATIOS MISLEAD; ANTIHYPERTENSIVE THERAPIES; VARIANCE PARAMETERS; PRIOR DISTRIBUTIONS; MULTIPLE-TREATMENTS; RELATIVE RISK; MISSING DATA; OUTCOMES; MODELS AB Background In the absence of sufficient data directly comparing multiple treatments, indirect comparisons using network meta-analyses (NMAs) can provide useful information. Under current contrast-based (CB) methods for binary outcomes, the patient-centered measures including the treatment-specific event rates and risk differences (RDs) are not provided, which may create some unnecessary obstacles for patients to comprehensively trade-off efficacy and safety measures. Purpose We aim to develop NMA to accurately estimate the treatment-specific event rates. Methods A Bayesian hierarchical model is developed to illustrate how treatment-specific event rates, RDs, and risk ratios (RRs) can be estimated. We first compare our approach to alternative methods using two hypothetical NMAs assuming a fixed RR or RD, and then use two published NMAs to illustrate the improved reporting. Results In the hypothetical NMAs, our approach outperforms current CB NMA methods in terms of bias. In the two published NMAs, noticeable differences are observed in the magnitude of relative treatment effects and several pairwise statistical significance tests from previous report. Limitations First, to facilitate the estimation, each study is assumed to hypothetically compare all treatments, with unstudied arms being missing at random. It is plausible that investigators may have selected treatment arms on purpose based on the results of previous trials, which may lead to 'nonignorable missingness' and potentially bias our estimates. Second, we have not considered methods to identify and account for potential inconsistency between direct and indirect comparisons. Conclusions The proposed NMA method can accurately estimate treatment-specific event rates, RDs, and RRs and is recommended. C1 [Zhang, Jing; Carlin, Bradley P.; Neaton, James D.; Chu, Haitao] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Soon, Guoxing G.; Nie, Lei] Off Biometr OTS CDER FDA, Div Biometr 4, Silver Spring, MD USA. [Kane, Robert; Virnig, Beth A.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN 55455 USA. RP Chu, HT (reprint author), Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. EM chux0051@umn.edu OI Chu, Haitao/0000-0003-0932-598X FU US NCI [1P01CA142538, 1R01-CA157458-01A1]; NIAID [AI103012]; US FDA FX H.C. is supported in part by the US NCI 1P01CA142538, NIAID AI103012, and a subcontract from the US FDA. B. P. C. is supported in part by the US NCI 1R01-CA157458-01A1 and NIAID AI103012. NR 62 TC 13 Z9 13 U1 2 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2014 VL 11 IS 2 BP 246 EP 262 DI 10.1177/1740774513498322 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AE0HT UT WOS:000333645300012 PM 24096635 ER PT J AU Haendiges, J Rock, M Myers, RA Brown, EW Evans, P Gonzalez-Escalona, N AF Haendiges, Julie Rock, Marvin Myers, Robert A. Brown, Eric W. Evans, Peter Gonzalez-Escalona, Narjol TI Pandemic Vibrio parahaemolyticus, Maryland, USA, 2012 SO EMERGING INFECTIOUS DISEASES LA English DT Letter ID GENOME SEQUENCE DATA C1 [Haendiges, Julie; Rock, Marvin; Myers, Robert A.] Dept Hlth & Mental Hyg, Baltimore, MD USA. [Brown, Eric W.; Evans, Peter; Gonzalez-Escalona, Narjol] US FDA, College Pk, MD 20740 USA. RP Gonzalez-Escalona, N (reprint author), US FDA, Ctr Food & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM narjol.gonzalez-escalona@fda.hhs.gov OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 NR 10 TC 12 Z9 14 U1 0 U2 6 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD APR PY 2014 VL 20 IS 4 BP 718 EP 720 DI 10.3201/eid2004.130818 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AD8GO UT WOS:000333504700034 PM 24655659 ER PT J AU Folster, JP Tolar, B Pecic, G Sheehan, D Rickert, R Hise, K Zhao, SH Fedorka-Cray, PJ McDermott, P Whichard, JM AF Folster, Jason P. Tolar, Beth Pecic, Gary Sheehan, Deborah Rickert, Regan Hise, Kelley Zhao, Shaohua Fedorka-Cray, Paula J. McDermott, Patrick Whichard, Jean M. TI Characterization of bla(CMY) Plasmids and Their Possible Role in Source Attribution of Salmonella enterica Serotype Typhimurium Infections SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID FIELD GEL-ELECTROPHORESIS; ESCHERICHIA-COLI; UNITED-STATES; BETA-LACTAMASES; INCI1 PLASMIDS; INCA/C PLASMID; FOOD ANIMALS; SUSCEPTIBILITY; RESISTANCE; PATHOGENS AB Salmonella is an important cause of foodborne illness; however, identifying the source of these infections can be difficult. This is especially true for Salmonella serotype Typhimurium, which is found in diverse agricultural niches. Extended-spectrum cephalosporins (ESC) are one of the primary treatment choices for complicated Salmonella infections. In Salmonella, ESC resistance in the United States is mainly mediated by bla(CMY) genes carried on various plasmids. In this study, we examined whether the characterization of bla(CMY) plasmids, along with additional information, can help us identify potential sources of infection by Salmonella, and used serotype Typhimurium as a model. In the United States, monitoring of retail meat, food animals, and ill persons for antimicrobial-resistant Salmonella is conducted by the National Antimicrobial Resistance Monitoring System. In 2008, 70 isolates (70/581; 12.0%) (34 isolates from retail meat, 23 food animal, and 13 human) were resistant to ceftriaxone and amoxicillin/clavulanic acid. All were polymerase chain reaction (PCR)-positive for bla(CMY) and 59/70 (84.3%) of these genes were plasmid encoded. PCR-based replicon typing identified 42/59 (71.2%) IncI1-bla(CMY) plasmids and 17/59 (28.8%) IncA/C-bla(CMY) plasmids. Isolates from chickens or chicken products with bla(CMY) plasmids primarily had IncI1-bla(CMY) plasmids (37/40; 92.5%), while all isolates from cattle had IncA/C-bla(CMY) plasmids. Isolates from humans had either IncA/C- bla(CMY) (n=8/12; [66.7%]) or IncI1- bla(CMY) (n=4/12 [33.3%]) plasmids. All of the IncI1-bla(CMY) plasmids were ST12 or were closely related to ST12. Antimicrobial susceptibility patterns (AST) and pulsed-field gel electrophoresis (PFGE) patterns of the isolates were also compared and differences were identified between isolate sources. When the source of a Typhimurium outbreak or sporadic illness is unknown, characterizing the outbreak isolate's bla(CMY) plasmids, AST, and PFGE patterns may help identify it. C1 [Folster, Jason P.; Tolar, Beth; Pecic, Gary; Sheehan, Deborah; Rickert, Regan; Hise, Kelley; Whichard, Jean M.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30329 USA. [Pecic, Gary] IHRC, Atlanta, GA USA. [Zhao, Shaohua; McDermott, Patrick] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. [Fedorka-Cray, Paula J.] ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, USDA, Athens, GA USA. RP Folster, JP (reprint author), Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, 1600 Clifton Rd NE,MS G29, Atlanta, GA 30329 USA. EM gux8@cdc.gov FU CDC; USDA; FDA Center for Veterinary Medicine FX We thank the NARMS participating public health laboratories for submitting the isolates, Anne Whitney for DNA sequencing, and Alessandra Carattoli for the plasmid incompatibility typing control strains. This work was partially supported by an interagency agreement between CDC, USDA, and the FDA Center for Veterinary Medicine. NR 28 TC 5 Z9 5 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 EI 1556-7125 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD APR 1 PY 2014 VL 11 IS 4 BP 301 EP 306 DI 10.1089/fpd.2013.1670 PG 6 WC Food Science & Technology SC Food Science & Technology GA AD9RR UT WOS:000333602700007 PM 24484290 ER PT J AU Mollan, TL Jia, YP Banerjee, S Wu, G Kreulen, RT Tsai, AL Olson, JS Crumbliss, AL Alayash, AI AF Mollan, Todd L. Jia, Yiping Banerjee, Sambuddha Wu, Gang Kreulen, R. Timothy Tsai, Ah-Lim Olson, John S. Crumbliss, Alvin L. Alayash, Abdu I. TI Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE EPR; Ferryl; Haptoglobin; Heme loss; Hemoglobin A; Iron(IV) oxo; Protein-based radical; Redox potential; Spectroelectrochemistry; Sulfhemoglobin; Free radicals ID OXIDATION-REDUCTION POTENTIALS; HEME-PROTEINS; HYDROGEN-PEROXIDE; BINDING; CHAINS; DISSOCIATION; MECHANISM; AUTOXIDATION; HAEMOGLOBIN; AFFINITY AB Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity and facilitates their rapid clearance from circulation after hemolysis. Humans possess three main phenotypes of Hp, designated Hp 1-1, Hp 2-1, and Hp 2-2. These variants exhibit diverse structural configurations and have been reported to be functionally nonequivalent. We have investigated the functional and redox properties of Hb-Hp complexes prepared using commercially fractionated Hp and found that all forms exhibit similar behavior. The rate of Hb dimer binding to Hp occurs with bimolecular rate constants of similar to 0.9 mu M-1 s(-1), irrespective of the type of Hp assayed. Although Hp binding does accelerate the observed rate of HbO(2) autoxidation by dissociating Hb tetramers into dimers, the rate observed for these bound dimers is three- to fourfold slower than that of Hb dimers free in solution. Co-incubation of ferric Hb with any form of Hp inhibits heme loss to below detectable levels. Intrinsic redox potentials (E-1/2) of the ferric/ferrous pair of each Hb-Hp complex are similar, varying from +54 to +59 mV (vs NHE), and are essentially the same as reported by us previously for Hb-Hp complexes prepared from unfractionated Hp. All Hb-Hp complexes generate similar high amounts of ferryl Hb after exposure to hydrogen peroxide. Electron paramagnetic resonance data indicate that the yields of protein-based radicals during this process are approximately 4 to 5% and are unaffected by the variant of Hp assayed. These data indicate that the Hp fractions examined are equivalent to one another with respect to Hb binding and associated stability and redox properties and that this result should be taken into account in the design of phenotype-specific Hp therapeutics aimed at countering Hb-mediated vascular disease. C1 [Mollan, Todd L.; Jia, Yiping; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. [Banerjee, Sambuddha; Kreulen, R. Timothy; Crumbliss, Alvin L.] Duke Univ, Dept Chem, Durham, NC 27708 USA. [Wu, Gang; Tsai, Ah-Lim] Univ Texas Houston, Sch Med, Dept Internal Med, Div Hematol, Houston, TX 77030 USA. [Olson, John S.] Rice Univ, Biochem & Cell Biol Dept, Houston, TX USA. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. EM abdu.alayash@fda.hhs.gov OI Olson, John/0000-0002-0760-5403 FU National Science Foundation [CHE 0809466]; Duke University; Welch Foundation Grant [C-0612]; U.S. Food and Drug Administration [MOD-SCI 2012]; National Institutes of Health [HL110900] FX The authors thank Eileen Singleton for her efforts in producing recombinant myoglobin, Francine Wood for assisting with Hb purification and catalase removal, Tigist Kassa for assistance at the bench, and Richard Chester from BPL for his assistance in Hp purification. The authors also thank Dr. Dimitri A. Svistunenko of Essex University for helpful discussions related to the EPR measurements of the protein radical. This work was supported by the National Institutes of Health under Grants HL110900 (A.I.A., J.S.O.) and HL095820 (A.-LT.), National Science Foundation Grant CHE 0809466 (A.L.C.), Duke University (A.L.C.), Welch Foundation Grant C-0612 (J.S.O.), and the U.S. Food and Drug Administration (MOD-SCI 2012, to A.I.A.). NR 73 TC 13 Z9 13 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR PY 2014 VL 69 BP 265 EP 277 DI 10.1016/j.freeradbiomed.2014.01.030 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AD8BC UT WOS:000333490500028 PM 24486321 ER PT J AU Bidzhieva, B Zagorodnyaya, T Karagiannis, K Simonyan, V Laassri, M Chumakov, K AF Bidzhieva, Bella Zagorodnyaya, Tatiana Karagiannis, Konstantinos Simonyan, Vahan Laassri, Majid Chumakov, Konstantin TI Deep sequencing approach for genetic stability evaluation of influenza A viruses SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Sequence heterogeneity; Profiles of mutations; Sequencing libraries preparation; Pyrosequencing; Illumina Solexa sequencing ID DEFECTIVE INTERFERING VIRUS; FULL-LENGTH AMPLIFICATION; VIRAL-RNA; VACCINE; LIVE; PROTECTION; GENOME; CELLS; MICE; DNA AB Assessment of genetic stability of viruses could be used to monitor manufacturing process of both live and inactivated viral vaccines. Until recently such studies were limited by the difficulty of detecting and quantifying mutations in heterogeneous viral populations. High-throughput sequencing technologies (deep sequencing) can generate massive amounts of genetic information and could be used to reveal and quantify mutations. Comparison of different approaches for deep sequencing of the complete influenza A genome was performed to determine the best way to detect and quantify mutants in attenuated influenza reassortant strain A/Brisbane/59/2007 (H1N1) and-its passages in different cell substrates. Full-length amplicons of influenza A virus segments as well as multiple overlapping amplicons covering the entire viral genome were subjected to several ways of DNA library preparation followed by deep sequencing using Solexa (Illumina) and pyroseguencing (454 Life Science) technologies. Sequencing coverage (the number of times each nucleotide was determined) of mutational profiles generated after 454-pyrosequencing of individually synthesized overlapping amplicons were relatively low and insufficiently uniform. Amplification of the entire genome of influenza virus followed by its enzymatic fragmentation, library construction, and Illumina sequencing resulted in high and uniform sequencing coverage enabling sensitive quantitation of mutations. A new bioinformatic procedure was developed to improve the post-alignment quality control for deep-sequencing data analysis. Published by Elsevier B.V. C1 [Bidzhieva, Bella; Zagorodnyaya, Tatiana; Karagiannis, Konstantinos; Simonyan, Vahan; Laassri, Majid; Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Laassri, M (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. EM majid.laassri@fda.hhs.gov NR 35 TC 3 Z9 4 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 EI 1879-0984 J9 J VIROL METHODS JI J. Virol. Methods PD APR PY 2014 VL 199 BP 68 EP 75 DI 10.1016/j.jviromet.2013.12.018 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA AE3CC UT WOS:000333853500011 PM 24406624 ER PT J AU Tsai, DH Cho, TJ DelRio, FW Gorham, JM Zheng, JW Tan, JJ Zachariah, MR Hackley, VA AF Tsai, De-Hao Cho, Tae Joon DelRio, Frank W. Gorham, Justin M. Zheng, Jiwen Tan, Jiaojie Zachariah, Michael R. Hackley, Vincent A. TI Controlled Formation and Characterization of Dithiothreitol-Conjugated Gold Nanoparticle Clusters SO LANGMUIR LA English DT Article ID THERMAL-DESORPTION SPECTROSCOPY; SELF-ASSEMBLED MONOLAYERS; MASS-SPECTROMETRY; DIMERS; NANOCLUSTERS; AU(111); FRACTIONATION; AGGREGATION; ADSORPTION; LIGANDS AB We report a systematic study of the controlled formation of discrete-sized gold nanoparticle clusters (GNCs) by interaction with the reducing agent dithiothreitol (DTT). Asymmetric-flow field flow fractionation and electrospray differential mobility analysis were employed complementarily to determine the particle size distributions of DTT-conjugated GNCs (DTT GNCs). Transmission electron microscopy was used to provide visualization of DTT GNCs at different states of aggregation. Surface packing density of DTT and the corresponding molecular conformation on the Au surface were characterized by inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy. Results show that DTT increases the aggregation rate of gold nanoparticles (AuNPs) up to approximate to 100 times. A mixed conformation (i.e., combining vertically aligned, horizontally aligned, and cross-linking modes) exists for DTT on the Au surface for all conditions examined. The primary size of AuNPs, concentration of DTT, and the starting concentration of AuNPs influence the degree of aggregation for DTT GNCs, indicating that the collision frequency, energy barrier, and surface density of DTT are the key factors that control the aggregation rate. DTT GNCs exhibit improved structural stability compared to the citrate-stabilized GNCs (i.e., unconjugated) following reaction with thiolated polyethylene glycol (SH-PEG), indicating that cross-linking and surface protection by DTT suppresses disaggregation normally induced by the steric repulsion of SH-PEG. This work describes a prototype methodology to form ligand-conjugated GNCs with high-quality and well-controlled material properties. C1 [Tsai, De-Hao; Cho, Tae Joon; DelRio, Frank W.; Gorham, Justin M.; Tan, Jiaojie; Hackley, Vincent A.] Natl Inst Stand & Technol, Mat Measurement Sci Div, Gaithersburg, MD 20899 USA. [Zachariah, Michael R.] Natl Inst Stand & Technol, Div Chem Sci, Gaithersburg, MD 20899 USA. [Zheng, Jiwen] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Tan, Jiaojie; Zachariah, Michael R.] Univ Maryland, Dept Chem Engn, College Pk, MD 20740 USA. [Tan, Jiaojie; Zachariah, Michael R.] Univ Maryland, Dept Chem, College Pk, MD 20740 USA. RP Hackley, VA (reprint author), Natl Inst Stand & Technol, Mat Measurement Sci Div, Gaithersburg, MD 20899 USA. EM vince.hackley@nist.gov OI Gorham, Justin/0000-0002-0569-297X NR 46 TC 12 Z9 12 U1 12 U2 94 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD APR 1 PY 2014 VL 30 IS 12 BP 3397 EP 3405 DI 10.1021/la500044y PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA AE2AT UT WOS:000333776400014 PM 24592809 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Evaluating patient, procedure, and provider characteristics as risk factors for postoperative complications SO SPINE JOURNAL LA English DT Letter ID OUTCOMES C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD APR PY 2014 VL 14 IS 4 BP 725 EP 726 DI 10.1016/j.spinee.2013.05.043 PG 3 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AD6YB UT WOS:000333406300027 PM 24655560 ER PT J AU Kim, B Hing, ZA Wu, A Schiller, T Struble, EB Liuwantara, D Kempert, PH Broxham, EJ Edwards, NC Marder, VJ Simhadri, VL Sauna, ZE Howard, TE Kimchi-Sarfaty, C AF Kim, Benjamin Hing, Zachary A. Wu, Andrew Schiller, Tal Struble, Evi B. Liuwantara, David Kempert, Pamela H. Broxham, Eric J. Edwards, Nathan C. Marder, Victor J. Simhadri, Vijaya L. Sauna, Zuben E. Howard, Tom E. Kimchi-Sarfaty, Chava TI Single-nucleotide variations defining previously unreported ADAMTS13 haplotypes are associated with differential expression and activity of the VWF-cleaving protease in a Salvadoran congenital thrombotic thrombocytopenic purpura family SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE haplotypes; congenital thrombotic thrombocytopenic purpura; phenotypes; quantitative trait nucleotides; ADAMTS13 ID MUTATIONS; DISEASE C1 [Kim, Benjamin] Univ Calif San Francisco, Sch Med, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA. [Hing, Zachary A.; Wu, Andrew; Schiller, Tal; Edwards, Nathan C.; Simhadri, Vijaya L.; Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, CBER, Bethesda, MD 20014 USA. [Struble, Evi B.] US FDA, Lab Plasma Derivat, Div Hematol, CBER, Bethesda, MD 20014 USA. [Liuwantara, David; Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Kempert, Pamela H.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Pediat, Los Angeles, CA 90095 USA. [Broxham, Eric J.; Howard, Tom E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. [Marder, Victor J.; Howard, Tom E.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Med, Los Angeles, CA 90095 USA. RP Kim, B (reprint author), Univ Calif San Francisco, Sch Med, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA. EM tom.howard@va.gov; chava.kimchi-sarfaty@fda.hhs.gov FU NHLBI NIH HHS [HL-72533, 1RC2-HL101851, HL-71130] NR 10 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2014 VL 165 IS 1 BP 154 EP 158 DI 10.1111/bjh.12713 PG 5 WC Hematology SC Hematology GA AC8BH UT WOS:000332757500020 PM 24433405 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Dosing in Children: A Critical Review of the Pharmacokinetic Allometric Scaling and Modelling Approaches in Paediatric Drug Development and Clinical Settings SO CLINICAL PHARMACOKINETICS LA English DT Review ID SYSTEMIC CLEARANCE PATHWAYS; MORPHINE MATURATION MODEL; BODY-SURFACE AREA; POPULATION PHARMACOKINETICS; ENERGY-METABOLISM; OBESE CHILDREN; PROPOFOL CLEARANCE; PREDICT CLEARANCE; DOSE SELECTION; MASS EXPONENT AB It should be recognized that children are not small adults, hence dosing in children should not be a 'small adult dose'. A mean population dose in all age groups is just an average dose and not necessarily the best or the correct dose for a given patient. The dose of a drug varies from patient to patient and individual adjustment of the dose is always ideal but is not always practical. Theoretically, dose selection in paediatric drug development or clinical settings can be done by using either body weight or the clearance of a drug. Over the years, a lot of approaches have been suggested for the prediction of drug clearance or dose in paediatrics. Although some proposed methods are useful for the prediction of clearance or dose in children, there remains a high degree of uncertainty in the prediction of drug clearance or dose in children. In particular, the prediction of clearance or dose in an individual patient remains highly erratic. This review takes a critical look at these approaches and highlights the application and limitations of these proposed methods. C1 US FDA, Div Hematol, OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Hematol, OBRR, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM iftekhar.mahmood@fda.hhs.gov NR 130 TC 20 Z9 20 U1 3 U2 15 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 EI 1179-1926 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD APR PY 2014 VL 53 IS 4 BP 327 EP 346 DI 10.1007/s40262-014-0134-5 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD4EY UT WOS:000333201600003 PM 24515100 ER PT J AU Melillo, AA Foreman, O Bosio, CM Elkins, KL AF Melillo, Amanda A. Foreman, Oded Bosio, Catharine M. Elkins, Karen L. TI T-bet Regulates Immunity to Francisella tularensis Live Vaccine Strain Infection, Particularly in Lungs SO INFECTION AND IMMUNITY LA English DT Article ID IFN-GAMMA PRODUCTION; INTRACELLULAR GROWTH; TRANSCRIPTION FACTOR; PULMONARY INFECTION; LINEAGE COMMITMENT; DISTINCT ROLES; CELL FUNCTION; CUTTING EDGE; MICE; LVS AB Upregulation of the transcription factor T-bet is correlated with the strength of protection against secondary challenge with the live vaccine strain (LVS) of Francisella tularensis. Thus, to determine if this mediator had direct consequences in immunity to LVS, we examined its role in infection. Despite substantial in vivo gamma interferon (IFN-gamma) levels, T-bet-knockout (KO) mice infected intradermally (i.d.) or intranasally (i.n.) with LVS succumbed to infection with doses 2 log units less than those required for their wild-type (WT) counterparts, and exhibited significantly increased bacterial burdens in the lung and spleen. Lungs of LVS-infected T-bet-KO mice contained fewer lymphocytes and more neutrophils and interleukin-17 than WT mice. LVS-vaccinated T-bet-KO mice survived lethal LVS intraperitoneal secondary challenge but not high doses of LVS i.n. challenge, independently of the route of vaccination. Immune T lymphocytes from the spleens of i.d. LVS-vaccinated WT or KO mice controlled intracellular bacterial replication in an in vitro coculture system, but cultures with T-bet-KO splenocyte supernatants contained less IFN-gamma and increased amounts of tumor necrosis factor alpha. In contrast, immune T-bet-KO lung lymphocytes were greatly impaired in controlling intramacrophage growth of LVS; this functional defect is the likely mechanism underpinning the lack of respiratory protection. Taken together, T-bet is important in host resistance to primary LVS infection and i.n. secondary challenge. Thus, T-bet represents a true, useful correlate for immunity to LVS. C1 [Melillo, Amanda A.; Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Foreman, Oded] Genentech Inc, San Francisco, CA 94080 USA. [Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT USA. RP Elkins, KL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM karen.elkins@fda.hhs.gov RI Bosio, Catharine/D-7456-2015 FU National Institute of Allergy and Infectious Diseases [Y1-AI-6153-01/224-06-1322]; Research Participation Program; Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration FX This work was supported in part by an interagency agreement with the National Institute of Allergy and Infectious Diseases (Y1-AI-6153-01/224-06-1322). This project was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 41 TC 6 Z9 6 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2014 VL 82 IS 4 BP 1477 EP 1490 DI 10.1128/IAI.01545-13 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AD4BX UT WOS:000333192300015 PM 24421047 ER PT J AU Abbey, CK Gallas, BD Boone, JM Niklason, LT Hadjiiski, LM Sahiner, B Samuelson, FW AF Abbey, Craig K. Gallas, Brandon D. Boone, John M. Niklason, Loren T. Hadjiiski, Lubomir M. Sahiner, Berkman Samuelson, Frank W. TI Comparative Statistical Properties of Expected Utility and Area Under the ROC Curve for Laboratory Studies of Observer Performance in Screening Mammography SO ACADEMIC RADIOLOGY LA English DT Article DE Expected utility; area under the ROC curve; observer performance studies ID CONTAMINATED BINORMAL MODEL; OPERATING CHARACTERISTIC CURVES; DORFMAN-BERBAUM-METZ; DIGITAL MAMMOGRAPHY; FILM MAMMOGRAPHY; MULTIREADER ROC; SOFT-COPY; ACCURACY; RADIOLOGISTS; METHODOLOGY AB Rationale and Objectives: Our objective is to determine whether expected utility (EU) and the area under the receiver operator characteristic (AUC) are consistent with one another as endpoints of observer performance-studies in mammography. These two measures characterize receiver operator characteristic performance somewhat differently. We compare these two study endpoints at the level of individual reader effects, statistical inference, and components of variance across readers and cases. Materials and Methods: We reanalyze three previously published laboratory observer performance studies that investigate various x-ray breast imaging modalities using EU and AUC. The EU measure is based on recent estimates of relative utility for screening mammography. Results: The AUC and EU measures are correlated across readers for individual modalities (r = 0.93) and differences in modalities (r = 0.94 to 0.98). Statistical inference for modality effects based on multi-reader multi-case analysis is very similar, with significant results (P < .05) in exactly the same conditions. Power analyses show mixed results across studies, with a small increase in power on average for EU that corresponds to approximately a 7% reduction in the number of readers. Despite a large number of crossing receiver operator characteristic curves (59% of readers), modality effects only rarely have opposite signs for EU and AUC (6%). Conclusions: We do not find any evidence of systematic differences between EU and AUC in screening mammography observer studies. Thus, when utility approaches are viable (i.e., an appropriate value of relative utility exists), practical effects such as statistical efficiency may be used to choose study endpoints. C1 [Abbey, Craig K.] Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA. [Gallas, Brandon D.; Sahiner, Berkman; Samuelson, Frank W.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD USA. [Boone, John M.] UC Davis Med Ctr, Dept Radiol, Sacramento, CA USA. [Niklason, Loren T.] Hologic Inc, Bedford, MA USA. [Hadjiiski, Lubomir M.] Univ Michigan, Ctr Comprehens Canc, Dept Radiol, Ann Arbor, MI 48109 USA. RP Abbey, CK (reprint author), Univ Calif Santa Barbara, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 USA. EM abbey@psych.ucsb.edu FU National Science Foundation (National Science Foundation-US Food and Drug Administration Scholar in Residence) [CBET-1238502]; National Institutes of Health [R01-EB002138] FX C.K.A. was supported by the National Science Foundation (National Science Foundation-US Food and Drug Administration Scholar in Residence: CBET-1238502). J.M.B. was supported by the National Institutes of Health grant number R01-EB002138. NR 39 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 2014 VL 21 IS 4 BP 481 EP 490 DI 10.1016/j.acra.2013.12.011 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD0JK UT WOS:000332920100009 PM 24594418 ER PT J AU Gonzalez-Escalona, N Timme, R Raphael, BH Zink, D Sharma, SK AF Gonzalez-Escalona, Narjol Timme, Ruth Raphael, Brian H. Zink, Donald Sharma, Shashi K. TI Whole-Genome Single-Nucleotide-Polymorphism Analysis for Discrimination of Clostridium botulinum Group I Strains SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SEROTYPE-A SUBTYPES; TOXIN; CLUSTERS; GENES; NEUROTOXINS; DIVERSITY; PLASMIDS; OUTBREAK; SEQUENCE; ORGANISM AB Clostridium botulinum is a genetically diverse Gram-positive bacterium producing extremely potent neurotoxins (botulinum neurotoxins A through G [BoNT/A-G]). The complete genome sequences of three strains harboring only the BoNT/A1 nucleotide sequence are publicly available. Although these strains contain a toxin cluster (HA(+) OrfX(-)) associated with hemagglutinin genes, little is known about the genomes of subtype A1 strains (termed HA(-) OrfX(+)) that lack hemagglutinin genes in the toxin gene cluster. We sequenced the genomes of three BoNT/A1-producing C. botulinum strains: two strains with the HA(+) OrfX(-) cluster (69A and 32A) and one strain with the HA(-) OrfX(+) cluster (CDC297). Whole-genome phylogenic single-nucleotide-polymorphism (SNP) analysis of these strains along with other publicly available C. botulinum group I strains revealed five distinct lineages. Strains 69A and 32A clustered with the C. botulinum type A1 Hall group, and strain CDC297 clustered with the C. botulinum type Ba4 strain 657. This study reports the use of whole-genome SNP sequence analysis for discrimination of C. botulinum group I strains and demonstrates the utility of this analysis in quickly differentiating C. botulinum strains harboring identical toxin gene subtypes. This analysis further supports previous work showing that strains CDC297 and 657 likely evolved from a common ancestor and independently acquired separate BoNT/A1 toxin gene clusters at distinct genomic locations. C1 [Gonzalez-Escalona, Narjol; Timme, Ruth; Sharma, Shashi K.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Zink, Donald] US FDA, Off Ctr Director, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Raphael, Brian H.] Ctr Dis Control & Prevent, Enter Dis Lab Branch, Atlanta, GA USA. RP Gonzalez-Escalona, N (reprint author), US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM narjol.gonzalez-escalona@fda.hhs.gov OI Raphael, Brian/0000-0003-2778-2623; Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU FDA Foods Program intramural funds FX This project was supported by FDA Foods Program intramural funds. NR 37 TC 12 Z9 12 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 2014 VL 80 IS 7 BP 2125 EP 2132 DI 10.1128/AEM.03934-13 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA AC9FV UT WOS:000332840700010 PM 24463972 ER PT J AU Bartal, G Vano, E Paulo, G Miller, DL AF Bartal, Gabriel Vano, Eliseo Paulo, Graciano Miller, Donald L. TI Management of Patient and Staff Radiation Dose in Interventional Radiology: Current Concepts SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review DE Dosimetry; Radiation protection; Radiation ID BRAIN-TUMORS; CARDIAC-CATHETERIZATION; OCCUPATIONAL-EXPOSURE; IONIZING-RADIATION; LENS OPACITIES; CATARACT RISK; IMAGE QUALITY; FOLLOW-UP; CARDIOLOGY; PERSONNEL AB The increasing complexity and numbers of interventional fluoroscopy procedures have led to increasing patient doses of radiation and to increasing concern over staff doses. Hybrid rooms incorporate multiple imaging modalities and are used by multidisciplinary teams in interventional fluoroscopy suites and operating theaters. These rooms present additional radiation protection challenges. The new low annual exposure limit for the lens of the eye also requires specific measures to prevent cataracts in operators. The traditional attitude of radiation protection must be changed to one of proactive management of radiation dose and image quality. Incorporation of a comprehensive dose management program into the departmental quality assurance program is now essential. Physicians, radiographers, and medical physicists play an essential role in the safe use of fluoroscopy in medical practice. Efficient use of all imaging modalities (e.g., fluoroscopy, digital subtraction angiography, cone-beam CT) requires knowledge of the effects of different equipment settings on patient and staff doses as well as the skill and competence to optimize these settings for each procedure and patient. Updates and recommendations on radiation protection and dose management programs, including aspects of education and training, are presented. C1 [Bartal, Gabriel] Meir MC, Dept Radiol, IL-44281 Kefar Sava, Israel. [Vano, Eliseo] Univ Complutense Madrid, Dept Radiol, Sch Med, Madrid 28040, Spain. [Paulo, Graciano] Coll Hlth Technol Coimbra, Coimbra, Portugal. [Miller, Donald L.] US FDA, Off In Vitro Diagnost & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Bartal, G (reprint author), Meir MC, Dept Radiol, 59 Tshernihovsky St, IL-44281 Kefar Sava, Israel. EM gbartal@gmail.com; eliseov@med.ucm.es; graciano@estescoimbra.pt; donald.miller@fda.hhs.gov OI Paulo, Graciano/0000-0001-6297-778X NR 80 TC 21 Z9 23 U1 2 U2 27 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 EI 1432-086X J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD APR PY 2014 VL 37 IS 2 BP 289 EP 298 DI 10.1007/s00270-013-0685-0 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AD2FI UT WOS:000333048800002 PM 23860936 ER PT J AU Yu, K Geng, XC Chen, MJ Zhang, J Wang, BS Ilic, K Tong, WD AF Yu, Ke Geng, Xingchao Chen, Minjun Zhang, Jie Wang, Bingshun Ilic, Katarina Tong, Weida TI High Daily Dose and Being a Substrate of Cytochrome P450 Enzymes Are Two Important Predictors of Drug-Induced Liver Injury SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID DICLOFENAC-ASSOCIATED HEPATOTOXICITY; IDIOSYNCRATIC HEPATOTOXICITY; COMMON PROPERTIES; PHARMACOKINETICS; FAILURE; GENDER; TRANSPLANTATION; DETERMINANT; METABOLISM; INDUCTION AB Drug-induced liver injury (DILI) is complicated and difficult to predict. It has been observed that drugs with extensive hepatic metabolism have a higher likelihood of causing DILI. Cytochrome P450 (P450) enzymes are primarily involved in hepatic metabolism. Identifying the associations of DILI with drugs that are P450 substrates, inhibitors, or inducers will be extremely helpful to clinicians during the decision-making process of caring for a patient suspected of having DILI. We collected metabolism data on P450 enzymes for 254 orally administered drugs in the Liver Toxicity Knowledge Base Benchmark Dataset with a known daily dose, and applied logistic regression to identify these associations. We revealed that drugs that are substrates of P450 enzymes have a higher likelihood of causing DILI [odds ratio (OR), 3.99; 95% confidence interval (95% CI), 2.07-7.67; P < 0.0001], which is dose-independent, and drugs that are P450 inhibitors have a higher likelihood of generating DILI only when they are administered at high daily doses (OR, 6.03; 95% CI, 1.32-27.5; P = 0.0098). However, drugs that are P450 inducers are not observed to be associated with DILI (OR, 1.55; 95% CI, 0.65-3.68; P = 0.3246). Our findings will be useful in identifying the suspected medication as a cause of liver injury in clinical settings. C1 [Yu, Ke; Chen, Minjun; Zhang, Jie; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Geng, Xingchao] Chinas State Food & Drug Adm, Natl Ctr Safety Evaluat Drugs, Natl Inst Food & Drug Control, Beijing, Peoples R China. [Wang, Bingshun] Shanghai Jiao Tong Univ, Sch Med, Dept Biostat, Shanghai 200030, Peoples R China. [Ilic, Katarina] Univ Belgrade, Dept Pharmacol, Fac Pharm, Belgrade, Serbia. RP Ilic, K (reprint author), Univ Belgrade, Dept Pharmacol, Fac Pharm, 450 Vojvode Stepe, Belgrade 11221, Serbia. EM katarina.v.ilic@gmail.com; weida.tong@fda.hhs.gov FU National Center for Toxicological Research (NCTR); Oak Ridge Institute for Science and Education (ORISE) through U.S. Department of Energy; U.S. Food and Drug Administration (FDA); FDA/NCTR Division of Bioinformatics and Biostatistics; ORISE; Chinese Ministry of Science and Technology [2012ZX09301001-006(003)]; Shanghai Jiao Tong University; Republic of Serbia Ministry of Education and Science [175064] FX K.Y. is supported by the Research Participation Program at the National Center for Toxicological Research (NCTR) administrated by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration (FDA). B.W. is supported by the FDA/NCTR Division of Bioinformatics and Biostatistics, ORISE, Chinese Ministry of Science and Technology [National Science and Technology Mega Project Grant 2012ZX09301001-006(003)], and Shanghai Jiao Tong University [K.C. Wong Medical Fellowship Fund]. K.I. worked at NCTR during her summer sabbatical and was supported by ORISE and the Republic of Serbia Ministry of Education and Science (Project 175064, 2011-2014). The views presented in this article do not reflect those of the FDA. Any mention of commercial products is for clarification and is not intended to constitute endorsement or recommendation for use. NR 33 TC 14 Z9 16 U1 1 U2 14 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 2014 VL 42 IS 4 BP 744 EP 750 DI 10.1124/dmd.113.056267 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AC9GN UT WOS:000332842500029 PM 24464804 ER PT J AU Epstein, SL Garcia, M AF Epstein, Suzanne L. Garcia, Mayra TI Survey of Human Antibody Responses to Influenza Virus Matrix Protein 2 by Use of a Sensitive Flow Cytometric Method SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material DE influenza; matrix 2; human antibodies; pandemic; seasonal; flow cytometry ID M2 PROTEIN; EXTRACELLULAR DOMAIN; MONOCLONAL-ANTIBODY; PROTECTIVE IMMUNITY; A VIRUSES; MICE; RESISTANCE; VACCINE; M2-PROTEIN; ECTODOMAIN C1 [Epstein, Suzanne L.; Garcia, Mayra] US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Epstein, SL (reprint author), US FDA, OCTGT, CBER, 1401 Rockville Pk,HFM 730, Rockville, MD 20852 USA. EM suzanne.epstein@fda.hhs.gov NR 16 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2014 VL 209 IS 7 BP 975 EP 977 DI 10.1093/infdis/jit813 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AD2TI UT WOS:000333087900001 PM 24325964 ER PT J AU Hewlett, EL Burns, DL Cotter, PA Harvill, ET Merkel, TJ Quinn, CP Stibitz, ES AF Hewlett, Erik L. Burns, Drusilla L. Cotter, Peggy A. Harvill, Eric T. Merkel, Tod J. Quinn, Conrad P. Stibitz, E. Scott TI Pertussis Pathogenesis-What We Know and What We Don't Know SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material DE Bordetella pertussis; pertussis; pathogenesis; virulence factors; whooping cough ID BORDETELLA-PERTUSSIS; INFECTION; TOXIN AB Pertussis is a worldwide public health threat. Bordetella pertussis produces multiple virulence factors that have been studied individually, and many have recently been found to have additional biological activities. Nevertheless, how they interact to cause the disease pertussis remains unknown. New animal models, particularly the infection of infant baboons with B. pertussis, are enabling longstanding questions about pertussis pathogenesis to be answered and new ones to be asked. Enhancing our understanding of pathogenesis will enable new approaches to the prevention and control of pertussis. C1 [Hewlett, Erik L.] Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA. [Hewlett, Erik L.] Univ Virginia, Sch Med, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA. [Burns, Drusilla L.; Merkel, Tod J.; Stibitz, E. Scott] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Cotter, Peggy A.] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Harvill, Eric T.] Penn State Univ, University Pk, PA 16802 USA. [Quinn, Conrad P.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. RP Hewlett, EL (reprint author), Univ Virginia, Sch Med, Box 800419, Charlottesville, VA 22908 USA. EM eh2v@virginia.edu FU NIAID NIH HHS [R01 AI094991, R01 AI018000, R01 AI18000]; NIGMS NIH HHS [R01 GM083113, R01 GM113681]; NIH HHS [P40 OD010988] NR 15 TC 21 Z9 23 U1 1 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2014 VL 209 IS 7 BP 982 EP 985 DI 10.1093/infdis/jit639 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AD2TI UT WOS:000333087900003 PM 24626533 ER PT J AU Burns, DL Meade, BD Messionnier, NE AF Burns, Drusilla L. Meade, Bruce D. Messionnier, Nancy E. TI Pertussis Resurgence: Perspectives From the Working Group Meeting on Pertussis on the Causes, Possible Paths Forward, and Gaps in Our Knowledge SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE pertussis; pertussis vaccines; vaccine effectiveness ID BORDETELLA-PERTUSSIS; WHOLE-CELL; UNITED-STATES; VACCINE; CHILDREN; APPEARANCE; PERTACTIN; RESPONSES; IMMUNITY; STRAINS C1 [Burns, Drusilla L.] US FDA, CBER, Bethesda, MD 20892 USA. [Meade, Bruce D.] Meade Biol, Hillsborough, NC USA. [Messionnier, Nancy E.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Burns, DL (reprint author), US FDA, CBER, HFM-434,8800 Rockville Pike, Bethesda, MD 20892 USA. EM drusilla.burns@fda.hhs.gov FU Food and Drug and Administration; Centers for Disease Control and Prevention FX This work was supported by the Food and Drug and Administration and Centers for Disease Control and Prevention. NR 25 TC 30 Z9 30 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2014 VL 209 SU 1 BP S32 EP S35 DI 10.1093/infdis/jit491 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AD2TN UT WOS:000333088400008 PM 24626870 ER PT J AU Farizo, KM Burns, DL Finn, TM Gruber, MF Pratt, RD AF Farizo, Karen M. Burns, Drusilla L. Finn, Theresa M. Gruber, Marion F. Pratt, R. Douglas TI Clinical Evaluation of Pertussis Vaccines: US Food and Drug Administration Regulatory Considerations SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE pertussis vaccines; regulatory pathways; vaccine effectiveness AB The resurgence of pertussis in the United States has stimulated considerable public health interest in developing new vaccination strategies to improve control of pertussis. The purpose of this article is to review the US Food and Drug Administration's regulatory framework for the prelicensure clinical evaluation of preventive vaccines and the clinical approaches that have been used to demonstrate effectiveness of US-licensed vaccines containing an acellular pertussis component. C1 [Farizo, Karen M.; Burns, Drusilla L.; Finn, Theresa M.; Gruber, Marion F.; Pratt, R. Douglas] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Farizo, KM (reprint author), US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM karen.farizo@fda.hhs.gov FU FDA FX The writing of this manuscript was supported by regular operational funds of the FDA. NR 10 TC 6 Z9 6 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2014 VL 209 SU 1 BP S28 EP S31 DI 10.1093/infdis/jit532 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AD2TN UT WOS:000333088400007 PM 24626869 ER PT J AU Merkel, TJ Halperin, SA AF Merkel, Tod J. Halperin, Scott A. TI Nonhuman Primate and Human Challenge Models of Pertussis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Animal models; Bacterial vaccines; Pertussis; Pulmonary infections ID EXPERIMENTAL WHOOPING-COUGH; BORDETELLA-PERTUSSIS AB Despite pertussis vaccination rates in excess of 95%, pertussis rates in the United States have been rising over the last 30 years, with increasingly larger outbreaks in 2004, 2010, and 2012. The reasons for this resurgence of pertussis are not clearly understood. The recent development of a baboon model of pertussis, along with the future development of a human challenge model of pertussis, has the potential to provide a path forward for answering critical questions about pertussis pathogenesis and host responses and will likely aid in the development of next-generation pertussis vaccines. C1 [Merkel, Tod J.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Halperin, Scott A.] Dalhousie Univ, Canadian Ctr Vaccinol, Halifax, NS, Canada. [Halperin, Scott A.] Dalhousie Univ, Dept Pediat, Halifax, NS, Canada. [Halperin, Scott A.] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS, Canada. RP Merkel, TJ (reprint author), US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bldg 29,Rm 419,29 Lincoln Dr, Bethesda, MD 20892 USA. EM tod.merkel@fda.hhs.gov FU NCRR NIH HHS [P40 RR012317]; NIH HHS [P40 OD010988] NR 20 TC 11 Z9 11 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2014 VL 209 SU 1 BP S20 EP S23 DI 10.1093/infdis/jit493 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AD2TN UT WOS:000333088400005 PM 24626867 ER PT J AU Yacobi, A Shah, VP Bashaw, ED Benfeldt, E Davit, B Ganes, D Ghosh, T Kanfer, I Kasting, GB Katz, L Lionberger, R Lu, GW Maibach, HI Pershing, LK Rackley, RJ Raw, A Shukla, CG Thakker, K Wagner, N Zovko, E Lane, ME AF Yacobi, Avraham Shah, Vinod P. Bashaw, Edward D. Benfeldt, Eva Davit, Barbara Ganes, Derek Ghosh, Tapash Kanfer, Isadore Kasting, Gerald B. Katz, Lindsey Lionberger, Robert Lu, Guang Wei Maibach, Howard I. Pershing, Lynn K. Rackley, Russell J. Raw, Andre Shukla, Chinmay G. Thakker, Kailas Wagner, Nathalie Zovko, Elizabeta Lane, Majella E. TI Current Challenges in Bioequivalence, Quality, and Novel Assessment Technologies for Topical Products SO PHARMACEUTICAL RESEARCH LA English DT Review DE bioequivalence; dermatologic topical product; generic; in vitro; in vivo; quality-by-design ID HUMAN SKIN; IN-VIVO; DERMATOPHARMACOKINETIC METHOD; CONCENTRATION PROFILES; STRATUM-CORNEUM; MICRODIALYSIS; FORMULATIONS; BIOAVAILABILITY; PENETRATION; ABSORPTION AB This paper summarises the proceedings of a recent workshop which brought together pharmaceutical scientists and dermatologists from academia, industry and regulatory agencies to discuss current regulatory issues and industry practices for establishing therapeutic bioequivalence (BE) of dermatologic topical products. The methods currently available for assessment of BE were reviewed as well as alternatives and the advantages and disadvantages of each method were considered. Guidance on quality and performance of topical products was reviewed and a framework to categorise existing and alternative methods for evaluation of BE was discussed. The outcome of the workshop emphasized both a need for greater attention to quality, possibly, via a Quality-By-Design (QBD) approach and a need to develop a "whole toolkit" approach towards the problem of determination of rate and extent in the assessment of topical bioavailability. The discussion on the BE and clinical equivalence of topical products revealed considerable concerns about the variability present in the current methodologies utilized by the industry and regulatory agencies. It was proposed that academicians, researchers, the pharmaceutical industry and regulators work together to evaluate and validate alternative methods that are based on both the underlying science and are adapted to the drug product itself instead of single "universal" method. C1 [Yacobi, Avraham] DOLE Pharma LLC, New York, NY USA. [Bashaw, Edward D.; Davit, Barbara; Ghosh, Tapash; Lionberger, Robert; Raw, Andre; Shukla, Chinmay G.] US FDA, Silver Spring, MD USA. [Benfeldt, Eva] Univ Copenhagen, Dept Dermatol, Roskilde Hosp, Copenhagen, Denmark. [Ganes, Derek] Ganes Pharma Inc, Toronto, ON, Canada. [Kanfer, Isadore] Rhodes Univ, ZA-6140 Grahamstown, South Africa. [Kasting, Gerald B.] Univ Cincinnati, Cincinnati, OH USA. [Katz, Lindsey] Biostudy Solut LLC, Wilmington, NC 28405 USA. [Lu, Guang Wei] Allergan, Irvine, CA USA. [Maibach, Howard I.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Pershing, Lynn K.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. [Rackley, Russell J.] Mylan Pharmaceut Inc, Morgantown, WV USA. [Thakker, Kailas] Tergus Pharma LLC, Durham, NC USA. [Wagner, Nathalie] Galderma R&D, Sophia Antipolis, France. [Zovko, Elizabeta] Forest Res Inst, New York, NY USA. [Lane, Majella E.] UCL, Sch Pharm, London, England. RP Lane, ME (reprint author), UCL, Sch Pharm, London, England. EM majella.lane@btinternet.com NR 37 TC 10 Z9 12 U1 3 U2 38 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 EI 1573-904X J9 PHARM RES-DORDR JI Pharm. Res. PD APR PY 2014 VL 31 IS 4 BP 837 EP 846 DI 10.1007/s11095-013-1259-1 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA AD2QL UT WOS:000333080100001 PM 24395404 ER PT J AU Ali, R Guo, XQ Lin, HX Khan, QM Ismail, M Waheed, U Ali, T Bhalli, JA AF Ali, Rahat Guo, Xiaoqing Lin, Haixia Khan, Qaiser M. Ismail, Muhammad Waheed, Usman Ali, Tayyaba Bhalli, Javed A. TI Mutant frequency in comparison to oxidative DNA damage induced by ochratoxin A in L5178Y tk(+/-) (3.7.2C) mouse lymphoma cells SO DRUG AND CHEMICAL TOXICOLOGY LA English DT Article DE Comet assay; mouse lymphoma assay; mutant frequency; ochratoxin A; oxidative DNA damage ID GENE MUTATION ASSAY; KIDNEY-CELLS; INTERNATIONAL WORKSHOP; MYCOTOXIN OCHRATOXIN; MUTAGENICITY TEST; A METABOLITES; RAT-KIDNEY; GENOTOXICITY; MICRONUCLEI; INDUCTION AB Ochratoxin A (OTA) is a naturally occurring mycotoxin that contaminates animal feed and human food. OTA is nephrotoxic, hepatotoxic, immunosuppressive and a potent renal carcinogen in rodents. In the present study, we evaluated the genotoxicity of OTA in L5178Y tk(+/-) (3.7.2C) mouse lymphoma cells using the microwell version of the mouse lymphoma gene mutation assay (MLA) and the comet assay modified to detect oxidative DNA damage. Cells were treated for 4 hours with 0, 5, 10, 25, 50 or 100 mu M of OTA in the presence and absence of exogenous metabolic activation (S9). Benzo[a]pyrene (1 mu g/mL) and 4-nitroquinoline-1-oxide (0.1 mu g/mL) were used as positive control with and without S9, respectively. OTA treatment produced dose-dependent increases in cytotoxicity and tk mutant frequency, with significant increases in mutant frequency detected at concentrations >= 25 mu M with and without S9. Similarly treated cells were used for the comet assay conducted with and without formamidopyrimidine-DNA glycosylase for the determination of oxidative DNA damage. OTA exposure resulted in a significant increase in both direct and oxidative DNA damage, with induction of oxidative damage being greater. The results indicate that OTA is mutagenic in mouse lymphoma assay; and that OTA-generated oxidative DNA damage is, at least partially, responsible for its mutagenicity in the assay. C1 [Ali, Rahat; Guo, Xiaoqing; Lin, Haixia; Bhalli, Javed A.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ali, Rahat; Khan, Qaiser M.; Ismail, Muhammad; Waheed, Usman; Ali, Tayyaba] Natl Inst Biotechnol & Genet Engn, Faisalabad, Pakistan. [Waheed, Usman] Univ Vet & Anim Sci, Dept Pathobiol, Lahore, Pakistan. [Ali, Tayyaba] GC Univ, Dept Zool & Fisheries, Faisalabad, Pakistan. RP Bhalli, JA (reprint author), Covance Labs Inc, 671 South Meridian Rd, Greenfield, IN 46140 USA. EM Javed.Bhalli@Covance.com RI Khan, Qaiser Mahmood/I-6401-2015; Lin, Haixia /J-4772-2015 FU Higher Education Commission (HEC), Pakistan FX The authors are thankful to Dr. Robert H. Heflich for supporting Rahat Ali at NCTR to conduct a part of his Ph.D. research work, which resulted in this manuscript. The authors are also thankful to the Higher Education Commission (HEC), Pakistan, for providing the financial support under the project "International Research Support Initiative Program (IRSIP)" and to the Oak Ridge Institute for Scientific Education (ORISE), for hosting the scientific interaction that resulted in this study. The views presented in this article do not necessarily reflect those of the U. S. Food and Drug Administration. NR 42 TC 3 Z9 3 U1 2 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0148-0545 EI 1525-6014 J9 DRUG CHEM TOXICOL JI Drug Chem. Toxicol. PD APR PY 2014 VL 37 IS 2 BP 227 EP 232 DI 10.3109/01480545.2013.838775 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology SC Chemistry; Pharmacology & Pharmacy; Toxicology GA AB8IZ UT WOS:000332034900015 PM 24164384 ER PT J AU Santillo, MF Liu, YT Ferguson, M Vohra, SN Wiesenfeld, PL AF Santillo, Michael F. Liu, Yitong Ferguson, Martine Vohra, Sanah N. Wiesenfeld, Paddy L. TI Inhibition of monoamine oxidase (MAO) by beta-carbolines and their interactions in live neuronal (PC12) and liver (HuH-7 and MH1C1) cells SO TOXICOLOGY IN VITRO LA English DT Article DE Combination index; Botanical; Harmine; Harmaline; Methylene blue; Cell assay ID HARMALA ALKALOIDS; METHYLENE-BLUE; IN-VITRO; FLUOROMETRIC-DETERMINATION; SEROTONIN TOXICITY; AMINE OXIDASE; PHARMACOKINETICS; METABOLISM; AYAHUASCA; HARMINE AB Interactions among monoamine oxidase (MAO) inhibitors in drugs, botanicals, and dietary supplements may lead to unpredictable neurochemical dysfunction due to excessive inhibition or therapeutic invalidation. Often recombinant MAO or brain tissue homogenates have been used to evaluate MAO inhibitors such as the beta-carboline alkaloids (harmane, harmine, harmaline, and harmalol). However, there is a lack of cellular systems for evaluation of MAO activity, which represents a more advanced in vitro model compared to recombinant enzymes or tissue lysates. Using kynuramine assays, intracellular MAO inhibition by beta-carbolines was measured in PC12 (rat pheochromocytoma), MH1C1 (rat liver), and HuH-7 (human liver) cell lines, which were compared with human recombinant MAO and cell lysates. beta-Carbolines (1 mu M, 90 min incubations) inhibited MAO by 40-99% in live PC12 cells where MAO A was the active isoform, and <12% in HuH-7 and MH1C1 cells where MAO B was primarily active. The combination index (CI), which serves as a quantitative indicator of pharmacological interactions, was determined for harmaline/harmine (CI, 1.01-1.25) and methylene blue/harmine (CI, 0.74-1.07) in PC12 cells. Overall, this study illustrates applications of cell-based in vitro assay platforms to gain a comprehensive understanding of intracellular MAO inhibitors and their interactions. Published by Elsevier Ltd. C1 [Santillo, Michael F.; Liu, Yitong; Vohra, Sanah N.; Wiesenfeld, Paddy L.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Ferguson, Martine] US FDA, Div Publ Hlth & Biostat, Off Analyt & Outreach, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Santillo, MF (reprint author), US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM michael.santillo@fda.hhs.gov RI Santillo, Michael/B-5081-2009; Liu, Yitong/H-2213-2011 OI Santillo, Michael/0000-0001-8087-5859; Liu, Yitong/0000-0002-4300-4349 FU appointment to the Research Participation Program at the U.S. Food and Drug Administration; U.S. Food and Drug Administration FX This work was supported in part by an appointment to the Research Participation Program at the U.S. Food and Drug Administration administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. Funding for this work was provided by the U.S. Food and Drug Administration. NR 54 TC 8 Z9 8 U1 1 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD APR PY 2014 VL 28 IS 3 BP 403 EP 410 DI 10.1016/j.tiv.2013.12.006 PG 8 WC Toxicology SC Toxicology GA AB8PZ UT WOS:000332053800009 PM 24373881 ER PT J AU Butler, J Fonarow, GC Zile, MR Lam, CS Roessig, L Schelbert, EB Shah, SJ Ahmed, A Bonow, RO Cleland, JGF Cody, RJ Chioncel, O Collins, SP Dunnmon, P Filippatos, G Lefkowitz, MP Marti, CN McMurray, JJ Misselwitz, F Nodari, S O'Connor, C Pfeffer, MA Pieske, B Pitt, B Rosano, G Sabbah, HN Senni, M Solomon, SD Stockbridge, N Teerlink, JR Georgiopoulou, VV Gheorghiade, M AF Butler, Javed Fonarow, Gregg C. Zile, Michael R. Lam, Carolyn S. Roessig, Lothar Schelbert, Erik B. Shah, Sanjiv J. Ahmed, Ali Bonow, Robert O. Cleland, John G. F. Cody, Robert J. Chioncel, Ovidiu Collins, Sean P. Dunnmon, Preston Filippatos, Gerasimos Lefkowitz, Martin P. Marti, Catherine N. McMurray, John J. Misselwitz, Frank Nodari, Savina O'Connor, Christopher Pfeffer, Marc A. Pieske, Burkert Pitt, Bertram Rosano, Giuseppe Sabbah, Hani N. Senni, Michele Solomon, Scott D. Stockbridge, Norman Teerlink, John R. Georgiopoulou, Vasiliki V. Gheorghiade, Mihai TI Developing Therapies for Heart Failure With Preserved Ejection Fraction Current State and Future Directions SO JACC-HEART FAILURE LA English DT Article DE epidemiology; heart failure; preserved ejection fraction; prognosis; treatment ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; VENTRICULAR DIASTOLIC DYSFUNCTION; CONVERTING ENZYME-INHIBITORS; PRIOR MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE LEVELS; SINGLE-BLIND TRIAL; EXERCISE CAPACITY; SYSTOLIC FUNCTION; ELDERLY-PATIENTS AB The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting. (C) 2014 by the American College of Cardiology Foundation C1 [Butler, Javed; Marti, Catherine N.; Georgiopoulou, Vasiliki V.] Emory Univ, Dept Med, Emory Cardiovasc Clin Res Inst, Atlanta, GA 30322 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Zile, Michael R.] Med Univ S Carolina, Div Cardiol, Charleston, SC 29425 USA. [Zile, Michael R.] RHJ Dept Vet Affairs Med Ctr, Charleston, SC USA. [Lam, Carolyn S.] Natl Univ Hlth Syst, Cardiovasc Res Inst, Singapore, Singapore. [Roessig, Lothar; Misselwitz, Frank] Bayer HealthCare, Global Clin Dev, Wuppertal, Germany. [Schelbert, Erik B.] Univ Pittsburgh, Dept Med, Med Ctr, Inst Heart & Vasc, Pittsburgh, PA USA. [Shah, Sanjiv J.; Bonow, Robert O.; Gheorghiade, Mihai] Northwestern Univ, Dept Med, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA. [Ahmed, Ali] Univ Alabama Birmingham, Div Gerontol, Birmingham, AL USA. [Cleland, John G. F.] Castle Hill Hosp, Hull York Med Sch, Dept Cardiol, Kingston Upon Hull, Yorks, England. [Cody, Robert J.] Janssen Pharmaceut, Cardiovasc & Metab Div, Raritan, NJ USA. [Chioncel, Ovidiu] Inst Emergency Cardiovasc Dis, Cardiol, Bucharest, Romania. [Collins, Sean P.] Vanderbilt Univ, Dept Emergency Med, Nashville, TN 37235 USA. [Dunnmon, Preston; Stockbridge, Norman] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Filippatos, Gerasimos] Athens Univ Hosp, Dept Cardiol, Athens, Greece. [Lefkowitz, Martin P.] Novartis Pharmaceut Inc, E Hanover, NJ USA. [McMurray, John J.] Univ Glasgow, Glasgow Cardiovasc Res Ctr, British Heart Fdn, Glasgow, Lanark, Scotland. [Nodari, Savina] Univ Brescia, Div Cardiol, Brescia, Italy. [O'Connor, Christopher] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Pfeffer, Marc A.; Solomon, Scott D.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Pieske, Burkert] Med Univ Graz, Dept Cardiol, Graz, Austria. [Pitt, Bertram] Univ Michigan, Sch Med, Dept Med, Div Cardiol, Ann Arbor, MI 48104 USA. [Rosano, Giuseppe] Ctr Clin & Basic Sci, Rome, Italy. [Sabbah, Hani N.] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. [Senni, Michele] Osped Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Butler, J (reprint author), Emory Clin, Cardiovasc Res Inst, 1462 Clifton Rd Northeast,Suite AT 504, Atlanta, GA 30322 USA. EM javed.butler@emory.edu OI chioncel, ovidiu/0000-0002-3197-3628; Cleland, John/0000-0002-1471-7016; mcmurray, john/0000-0002-6317-3975 FU NHLBI NIH HHS [U10 HL110302] NR 93 TC 66 Z9 67 U1 3 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD APR PY 2014 VL 2 IS 2 BP 97 EP 112 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4CX UT WOS:000365647100002 PM 24720916 ER PT J AU Johannesen, L Garnett, CE Targum, S Lee, JY Soerensen, JS Mehrotra, N AF Johannesen, Lars Garnett, Christine E. Targum, Shari Lee, Joo-Yeon Soerensen, Jens Stampe Mehrotra, Nitin TI IMPROVING OUR UNDERSTANDING OF THE RELATIONSHIP BETWEEN QT PROLONGATION AND RISK OF TORSADE DE POINTES USING A QUANTITATIVE MODELING APPROACH SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 [Johannesen, Lars; Garnett, Christine E.; Targum, Shari; Lee, Joo-Yeon; Soerensen, Jens Stampe; Mehrotra, Nitin] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 1 PY 2014 VL 63 IS 12 SU S MA 1107-95 BP A305 EP A305 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP0QC UT WOS:000359579100306 ER PT J AU Zusterzeel, R Curtis, J Canos, D Sanders, WE Selzman, KA Pina, I Spatz, E Bao, H Ponirakis, A Varosy, P Masoudi, F Strauss, D AF Zusterzeel, Robbert Curtis, Jeptha Canos, Daniel Sanders, William E. Selzman, Kimberly A. Pina, Ileana Spatz, Erica Bao, Haikun Ponirakis, Angelo Varosy, Paul Masoudi, Frederick Strauss, David TI SEX-SPECIFIC MORTALITY RISK BY QRS MORPHOLOGY AND DURATION IN PATIENTS RECEIVING CARDIAC RESYNCHRONIZATION THERAPY: RESULTS FROM THE NCDR (R) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 [Zusterzeel, Robbert; Curtis, Jeptha; Canos, Daniel; Sanders, William E.; Selzman, Kimberly A.; Pina, Ileana; Spatz, Erica; Bao, Haikun; Ponirakis, Angelo; Varosy, Paul; Masoudi, Frederick; Strauss, David] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 1 PY 2014 VL 63 IS 12 SU S MA 1128M-362A BP A719 EP A719 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP0QC UT WOS:000359579101377 ER PT J AU Mohamed, T Zhao, SH White, DG Parveen, S AF Mohamed, Tagelsir Zhao, Shaohua White, David G. Parveen, Salina TI Molecular characterization of antibiotic resistant Salmonella Typhimurium and Salmonella Kentucky isolated from pre- and post-chill whole broilers carcasses SO FOOD MICROBIOLOGY LA English DT Article DE Salmonella Typhimurium; Salmonella Kentucky; Pre- and post-chill; Pulsed-field gel electrophoresis; Virulence factors ID ESCHERICHIA-COLI; UNITED-STATES; ANTIMICROBIAL RESISTANCE; AEROBACTIN PRODUCTION; VIRULENCE PLASMID; PROCESSED POULTRY; FOOD ANIMALS; CHICKEN MEAT; GENES; CELLS AB There is conflicting data regarding whether commercial chilling has any effect on persistence of Salmonella serovars, including antibiotic resistant variants, on chicken carcasses. A total of 309 Salmonella Typhimurium and Salmonella Kentucky isolates recovered from pre- and post-chill whole broiler carcasses were characterized for genetic relatedness using Pulsed Field Gel Electrophoresis (PFGE) and for the presence of virulence factors (invA, pagC, spvC) by PCR and for aerobactin and colicin production by bioassays. A subset of these isolates (n = 218) displaying resistance to either sulfisoxazole and/or ceftiofur [S. Typhimurium (n = 66) and S. Kentucky (n = 152)] were further tested for the presence of associated antibiotic resistance elements (class-I integrons and bla(CMY) genes) by PCR. All 145 ceftiofur resistant S. Kentucky and S. Typhimurium isolates possessed bla(CMY) genes. Class-I integrons were only detected in 6.1% (n = 4/66) of sulfisoxazole resistant S. Typhimurium isolates. The PFGE analysis revealed the presence of genetically diverse populations within the recovered isolates but clusters were generally concordant with serotypes and antimicrobial resistance profiles. At a 100% pattern similarity index, thirty-six percent of the undistinguishable S. Typhimurium and 22% of the undistinguishable S. Kentucky isolates were recovered from the same chilling step. All isolates possessed the invA and pagC genes, but only 1.4%possessed spvC. Irrespective of the chilling step, there was a significant difference (P < 0.05) in the production of aerobactin and colicin between S. Typhimurium and S. Kentucky isolates. Taken together, these results indicate that chilling impacted the recovery of particular Salmonella clonal groups but had no effect on the presence of class-I integrons, bla(CMY) genes, and tested virulence factors. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Mohamed, Tagelsir; Parveen, Salina] Univ Maryland Eastern Shore, Ctr Food Sci & Technol 2116, Dept Agr Food & Resource Sci, Food Sci & Technol PhD Program, Princess Anne, MD 21863 USA. [Zhao, Shaohua; White, David G.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Veterinaiy Med, Laurel, MD 20708 USA. RP Parveen, S (reprint author), Univ Maryland Eastern Shore, Ctr Food Sci & Technol 2116, Dept Agr Food & Resource Sci, Food Sci & Technol PhD Program, Princess Anne, MD 21863 USA. EM sparveen@umes.edu FU USDA Evans-Allen FX The research was supported by the USDA Evans-Allen. We are grateful to Ms. Sharon Friedman Microbiologist, CVM, FDA, Laurel, Maryland, Dr. M. Santin and Ms. C. Lam, EMFSL Beltsville, Maryland for technical assistance. We are also indebted to Dr. Anthony Nyame and his students Ms. Nelum Dorabawila and Ms. Msano Mandalasi, Department of Natural Sciences, University of Maryland Eastern Shore to allowing us to use their Camera, Dr. Catherine Logue and Ms. Julie Sherwood, North Dakota State University for providing us positive and negative control strains used in the bioassays. We are grateful to Drs. Thomas Oscar and Jeff Karns, USDA, ARS, and Ms. Chanelle White, Ms. Rizwana Tasmin, Drs. Jurgen Schwarz and Fawzy Hashem, Food Science and Technology Ph.D. Program, University of Maryland Eastern Shore for their helpful suggestions. NR 51 TC 10 Z9 10 U1 3 U2 99 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD APR PY 2014 VL 38 BP 6 EP 15 DI 10.1016/j.fm.2013.08.002 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 275EZ UT WOS:000328660400002 PM 24290620 ER PT J AU Mezal, EH Sabol, A Khan, MA Ali, N Stefanova, R Khan, AA AF Mezal, Ezat H. Sabol, Ashley Khan, Mariam A. Ali, Nawab Stefanova, Rossina Khan, Ashraf A. TI Isolation and molecular characterization of Salmonella enterica serovar Enteritidis from poultry house and clinical samples during 2010 SO FOOD MICROBIOLOGY LA English DT Article DE Salmonella Enteritidis; MLVA; Pulsed-field gel electrophoresis; Plasmid ID FIELD GEL-ELECTROPHORESIS; UNITED-STATES; IMPORTED SEAFOOD; SEROTYPE ENTERITIDIS; ESCHERICHIA-COLI; VARIABLE-NUMBER; RESISTANCE; FOOD; PCR; IDENTIFICATION AB A total of 60 Salmonella enterica serovar (ser.) Enteritidis isolates, 28 from poultry houses and 32 from clinical samples, were isolated during 2010. These isolates were subjected to testing and analyzed for antibiotic resistance, virulence genes, plasmids and plasmid replicon types. To assess genetic diversity, pulsed-field gel electrophoresis (PFGE) fingerprinting, using the Xbal restriction enzyme, Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA) and plasmid profiles were performed. All isolates from poultry, and 10 out of 32 clinical isolates were sensitive to ampicillin, chloramphenicol, gentamicin, kanamycin, nalidixic acid, sulfisoxazole, streptomycin, and tetracycline. Twenty-one of thirty-two clinical isolates were resistant to ampicillin and tetracycline, and one isolate was resistant to nalidixic acid. PFGE typing of sixty ser. Enteritidis isolates by Xbal resulted in 10-12 bands and grouped into six clusters each with similarity from 95% to 81%. The MLVA analysis of sixty isolates gave 18 allele profiles with the majority of isolates displayed in three groups, and two clinical isolates found to be new in the PulseNet national MLVA database. All isolates were positive for 12 or more of the 17 virulence genes mostly found in S. enterica (spvB, spiA, pagC, msgA, invA, sipB, prgH, spaN, orgA, tolC, iroN, sitC, lpfC, sifA, sopB, and pefA) and negative for one gene (cdtB). All isolates carried a typical 58 kb plasmid, type Inc/FIIA. Three poultry isolates and one clinical isolate carried small plasmids with 3.8, 6, 7.6 and 11.5 kb. Ten of the clinical isolates carried plasmids, with sizes 36 and 38 kb, types IncL/M and IncN, and one isolate carried an 81 kb plasmid, type Incl. Southern hybridization of a plasmid with an Inc/FIIA gene probe hybridized one large 58 kb plasmid in all isolates. Several large and small plasmids from poultry isolates were not typed by our PCR-based method. These results confirmed that PFGE fingerprinting has limited discriminatory power for ser. Enteritidis in both poultry and clinical sources. However, the plasmid and MLVA allele profiles were a useful and important epidemiology tool to discriminate outbreak strains of set. Enteritidis from poultry and clinical samples. Published by Elsevier Ltd. C1 [Mezal, Ezat H.; Khan, Ashraf A.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Mezal, Ezat H.; Ali, Nawab] Univ Arkansas, Little Rock, AR 72205 USA. [Sabol, Ashley] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Khan, Mariam A.] Univ Cent Arkansas, Conway, AR USA. [Stefanova, Rossina] Arkansas Dept Hlth, Little Rock, AR 72205 USA. [Mezal, Ezat H.] Univ Thi Qar, Coll Sci, Dept Biol, Thi Qar, Iraq. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM ashraf.khan@hotmail.com NR 39 TC 12 Z9 14 U1 1 U2 89 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD APR PY 2014 VL 38 BP 67 EP 74 DI 10.1016/j.fm.2013.08.003 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 275EZ UT WOS:000328660400010 PM 24290628 ER PT J AU Park, SH Aydin, M Khatiwara, A Dolan, MC Gilmore, DF Bouldin, JL Ahn, S Ricke, SC AF Park, Si Hong Aydin, Muhsin Khatiwara, Anita Dolan, Maureen C. Gilmore, David F. Bouldin, Jennifer L. Ahn, Soohyoun Ricke, Steven C. z TI Current and emerging technologies for rapid detection and characterization of Salmonella in poultry and poultry products SO FOOD MICROBIOLOGY LA English DT Review DE Salmonella; Rapid detection; Characterization; Poultry ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; ENTERICA SEROVAR TYPHIMURIUM; ANTIMICROBIAL RESISTANCE GENES; ESCHERICHIA-COLI O157-H7; MULTIPLEX DNA AMPLIFICATION; LINKED-IMMUNOSORBENT-ASSAY; UNITED-STATES; OLIGONUCLEOTIDE MICROARRAY; IMMUNOMAGNETIC SEPARATION AB Salmonella is the leading cause of foodborne illnesses in the United States, and one of the main contributors to salmonellosis is the consumption of contaminated poultry and poultry products. Since deleterious effects of Salmonella on public health and the economy continue to occur, there is an ongoing need to develop more advanced detection methods that can identify Salmonella accurately and rapidly in foods before they reach consumers. Rapid detection and identification methods for Salmonella are considered to be an important component of strategies designed to prevent poultry and poultry product-associated illnesses. In the past three decades, there have been increasing efforts towards developing and improving rapid pathogen detection and characterization methodologies for application to poultry and poultry products. In this review, we discuss molecular methods for detection, identification and genetic characterization of Salmonella associated with poultry and poultry products. In addition, the advantages and disadvantages of the established and emerging rapid detection and characterization methods are addressed for Salmonella in poultry and poultry products. The methods with potential application to the industry are highlighted in this review. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Park, Si Hong; Ricke, Steven C. z] Univ Arkansas, Dept Food Sci, Cell & Mol Biol Program, Fayetteville, AR 72704 USA. [Park, Si Hong; Ricke, Steven C. z] Univ Arkansas, Dept Food Sci, Ctr Food Safety, Fayetteville, AR 72704 USA. [Aydin, Muhsin] Arkansas State Univ, Mol Biosci Program, Jonesboro, AR USA. [Khatiwara, Anita] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Dolan, Maureen C.] Arkansas State Univ, Arkansas Biosci Inst, Jonesboro, AR USA. [Gilmore, David F.] Arkansas State Univ, Dept Biol Sci, Jonesboro, AR USA. [Bouldin, Jennifer L.] Arkansas State Univ, Ecotoxicol Res Facil, Jonesboro, AR USA. [Ahn, Soohyoun] Univ Florida, Food Sci & Human Nutr Dept, Gainesville, FL USA. RP Ricke, SC (reprint author), Univ Arkansas, Dept Food Sci, Ctr Food Safety, Fayetteville, AR 72704 USA. EM sricke@uark.edu RI Aydin, Muhsin/L-3791-2013 FU Vivione Biosciences, Pine Bluff, AR FX We thank the University of Arkansas, Fayetteville, Cell and Molecular Biology (CEMB) program for supporting a graduate student assistantship to SHP. We would also like to acknowledge partial support of SHP by Vivione Biosciences, Pine Bluff, AR. NR 205 TC 23 Z9 25 U1 5 U2 120 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD APR PY 2014 VL 38 BP 250 EP 262 DI 10.1016/j.fm.2013.10.002 PG 13 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 275EZ UT WOS:000328660400031 PM 24290649 ER PT J AU George, NI Chang, CW AF George, Nysia I. Chang, Ching-Wei TI DAFS: a data-adaptive flag method for RNA-sequencing data to differentiate genes with low and high expression SO BMC BIOINFORMATICS LA English DT Article DE RNA-sequencing; Low expression; Data-adaptive; Flag; Mixture distribution ID MESSENGER-RNA; SEQ DATA; ABUNDANCE; MODEL; PROTEINS; CELLS AB Background: Next-generation sequencing (NGS) has advanced the application of high-throughput sequencing technologies in genetic and genomic variation analysis. Due to the large dynamic range of expression levels, RNA-seq is more prone to detect transcripts with low expression. It is clear that genes with no mapped reads are not expressed; however, there is ongoing debate about the level of abundance that constitutes biologically meaningful expression. To date, there is no consensus on the definition of low expression. Since random variation is high in regions with low expression and distributions of transcript expression are affected by numerous experimental factors, methods to differentiate low and high expressed data in a sample are critical to interpreting classes of abundance levels in RNA-seq data. Results: A data-adaptive approach was developed to estimate the lower bound of high expression for RNA-seq data. The Kolmgorov-Smirnov statistic and multivariate adaptive regression splines were used to determine the optimal cutoff value for separating transcripts with high and low expression. Results from the proposed method were compared to results obtained by estimating the theoretical cutoff of a fitted two-component mixture distribution. The robustness of the proposed method was demonstrated by analyzing different RNA-seq datasets that varied by sequencing depth, species, scale of measurement, and empirical density shape. Conclusions: The analysis of real and simulated data presented here illustrates the need to employ data-adaptive methodology in lieu of arbitrary cutoffs to distinguish low expressed RNA-seq data from high expression. Our results also present the drawbacks of characterizing the data by a two-component mixture distribution when classes of gene expression are not well separated. The ability to ascertain stably expressed RNA-seq data is essential in the filtering process of data analysis, and methodologies that consider the underlying data structure demonstrate superior performance in preserving most of the interpretable and meaningful data. The proposed algorithm for classifying low and high regions of transcript abundance promises wide-range application in the continuing development of RNA-seq analysis. C1 [George, Nysia I.; Chang, Ching-Wei] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. RP Chang, CW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. EM Ching-Wei.Chang@fda.hhs.gov NR 39 TC 3 Z9 3 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAR 31 PY 2014 VL 15 AR 92 DI 10.1186/1471-2105-15-92 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA AF2OI UT WOS:000334551000001 PM 24685233 ER PT J AU Alam, MS Kuo, JL Ernst, PB Derr-Castillo, V Pereira, M Gaines, D Costales, M Bigley, E Williams, K AF Alam, M. Samiul Kuo, Jennifer L. Ernst, Peter B. Derr-Castillo, Victoria Pereira, Marion Gaines, Dennis Costales, Matthew Bigley, Elmer Williams, Kristina TI Ecto-5 '-Nucleotidase (CD73) Regulates Host Inflammatory Responses and Exacerbates Murine Salmonellosis SO SCIENTIFIC REPORTS LA English DT Article ID CD4 T-CELLS; NITRIC-OXIDE SYNTHASE; ADENOSINE GENERATION; CYTOKINE PRODUCTION; IMMUNE SUPPRESSION; PHAGOCYTE OXIDASE; INDUCED GASTRITIS; TYPHOID-FEVER; HELPER-CELLS; IFN-GAMMA AB Food-borne Salmonella spp., are a major cause of hospitalization and death. Adenosine, an important immune regulator of inflammation, limits tissue damage during infection. CD39 (nucleoside triphosphate dephosphorylase) combined with ecto-5'-nucleotidase (CD73) metabolizes ATP to adenosine. We studied the expressions of CD39 and CD73 in tissues, and T helper cells in mice after Salmonella infection and evaluated the role of CD73 in regulating immune responses and bacterial clearance in wild-type and CD73-deficient (CD73(-/-)) mice. Both CD39 and CD73 transcript levels declined in the infected wild-type mice. Compared to wild-type mice, tissues from infected CD73(-/-) mice had significantly higher expression of pro-inflammatory cytokines and reduced anti-inflammatory responses. CD73(-/-) mice were more resistant to infection and had a greater inflammatory responses and a significantly lower bacterial load in the liver compared to wild-type mice. Thus, CD73 expression attenuates inflammation during murine Salmonellosis and impairs immunity, leading to increased bacterial colonization and prolonged infection. C1 [Alam, M. Samiul; Kuo, Jennifer L.; Pereira, Marion; Gaines, Dennis; Costales, Matthew; Bigley, Elmer; Williams, Kristina] US FDA, Immunobiol Branch, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Ernst, Peter B.; Derr-Castillo, Victoria] Univ Calif San Diego, Div Comparat Pathol & Med, San Diego, CA 92093 USA. RP Alam, MS (reprint author), US FDA, Immunobiol Branch, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM Mohammad.alam@fda.hhs.gov FU Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration FX This research was supported by the intramural research program for the Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration. The authors are grateful to Dr. Linda Thompson for providing us with the CD73-deficient mouse breeding pairs. NR 49 TC 6 Z9 7 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD MAR 27 PY 2014 VL 4 AR 4486 DI 10.1038/srep04486 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AD7QU UT WOS:000333460500007 PM 24670982 ER PT J AU Wu, TJ Shamsaddini, A Pan, Y Smith, K Crichton, DJ Simonyan, V Mazumder, R AF Wu, Tsung-Jung Shamsaddini, Amirhossein Pan, Yang Smith, Krista Crichton, Daniel J. Simonyan, Vahan Mazumder, Raja TI A framework for organizing cancer-related variations from existing databases, publications and NGS data using a High-performance Integrated Virtual Environment (HIVE) SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID PROTEIN INFORMATION RESOURCE; HUMAN GENOME; BIOTECHNOLOGY INFORMATION; CLASSIFICATION-SYSTEM; REFERENCE SEQUENCES; SOMATIC MUTATIONS; NATIONAL CENTER; READ ALIGNMENT; BIG DATA; ANNOTATION AB Years of sequence feature curation by UniProtKB/Swiss-Prot, PIR-PSD, NCBI-CDD, RefSeq and other database biocurators has led to a rich repository of information on functional sites of genes and proteins. This information along with variation-related annotation can be used to scan human short sequence reads from next-generation sequencing (NGS) pipelines for presence of non-synonymous single-nucleotide variations (nsSNVs) that affect functional sites. This and similar workflows are becoming more important because thousands of NGS data sets are being made available through projects such as The Cancer Genome Atlas (TCGA), and researchers want to evaluate their biomarkers in genomic data. BioMuta, an integrated sequence feature database, provides a framework for automated and manual curation and integration of cancer-related sequence features so that they can be used in NGS analysis pipelines. Sequence feature information in BioMuta is collected from the Catalogue of Somatic Mutations in Cancer (COSMIC), ClinVar, UniProtKB and through biocuration of information available from publications. Additionally, nsSNVs identified through automated analysis of NGS data from TCGA are also included in the database. Because of the petabytes of data and information present in NGS primary repositories, a platform HIVE (High-performance Integrated Virtual Environment) for storing, analyzing, computing and curating NGS data and associated metadata has been developed. Using HIVE, 31 979 nsSNVs were identified in TCGA-derived NGS data from breast cancer patients. All variations identified through this process are stored in a Curated Short Read archive, and the nsSNVs from the tumor samples are included in BioMuta. Currently, BioMuta has 26 cancer types with 13 896 small-scale and 308 986 large-scale study-derived variations. Integration of variation data allows identifications of novel or common nsSNVs that can be prioritized in validation studies. C1 [Wu, Tsung-Jung; Shamsaddini, Amirhossein; Pan, Yang; Smith, Krista; Mazumder, Raja] George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA. [Crichton, Daniel J.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA. [Simonyan, Vahan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Mazumder, Raja] George Washington Univ, McCormick Genom & Prote Ctr, Washington, DC 20037 USA. RP Mazumder, R (reprint author), George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA. EM mazumder@gwu.edu OI Pan, Yang/0000-0003-3487-7233 FU National Institutes of Health [U01 CA168926]; George Washington University FX U01 CA168926 (in part) National Institutes of Health and George Washington University funds. Funding for open access charge: George Washington University. NR 55 TC 15 Z9 16 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD MAR 25 PY 2014 AR bau022 DI 10.1093/database/bau022 PG 11 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA AD8OV UT WOS:000333526400001 ER PT J AU Yang, X Weng, ZQ Mendrick, DL Shi, Q AF Yang, Xi Weng, Zuquan Mendrick, Donna L. Shi, Qiang TI Circulating extracellular vesicles as a potential source of new biomarkers of drug-induced liver injury SO TOXICOLOGY LETTERS LA English DT Review DE Drug-induced liver injury; Biomarkers; Extracellular vesicles; Exosomes ID MESSENGER-RNAS; MECHANISTIC BIOMARKERS; MICRORNA PROFILES; EXOSOME ISOLATION; HUMAN PLASMA; HEPATOTOXICITY; IDENTIFICATION; HEPATOCYTES; BLOOD; CELLS AB Like most cell types, hepatocytes constantly produce extracellular vesicles (EVs) such as exosomes and microvesicles that are released into the circulation to transport signaling molecules and cellular waste. Circulating EVs are being vigorously explored as biomarkers of diseases and toxicities, including drug-induced liver injury (DILI). Emerging data suggest that (a) blood-borne EVs contain liver-specific mRNAs and microRNAs (miRNAs), (b) the levels can be remarkably elevated in response to DILI, and (c) the increases correlate well with classical measures of liver damage. The expression profile of mRNAs in EVs and the compartmentalization of miRNAs within EVs or other blood fractions were found to be indicative of the offending drug involved in DILI, thus providing more informative assessment of liver injury than using alanine aminotransferase alone. EVs in the urine and cell culture medium were also found to contain proteins or mRNAs that were indicative of DILI. However, major improvements in EV isolation methods are needed for the discovery, evaluation, and quantification of possible DILI biomarkers in circulating EVs. Published by Elsevier Ireland Ltd. C1 [Yang, Xi; Weng, Zuquan; Mendrick, Donna L.; Shi, Qiang] Food & Drug Adm, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Shi, Q (reprint author), Food & Drug Adm, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Qiang.Shi@fda.hhs.gov FU US FDA's Chief Scientist's Challenge Grants program; Research Participation Program at the National Center for Toxicological Research FX This study is supported by the US FDA's Chief Scientist's Challenge Grants program. Dr. Zuquan Weng is supported by the Research Participation Program at the National Center for Toxicological Research administrated by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. NR 56 TC 14 Z9 16 U1 0 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR 21 PY 2014 VL 225 IS 3 BP 401 EP 406 DI 10.1016/j.toxlet.2014.01.013 PG 6 WC Toxicology SC Toxicology GA AB3YF UT WOS:000331725400009 PM 24462978 ER PT J AU Jerse, AE Bash, MC Russell, MW AF Jerse, Ann E. Bash, Margaret C. Russell, Michael W. TI Vaccines against gonorrhea: Current status and future challenges SO VACCINE LA English DT Article DE Immunity; T cells; Antibodies; Immune regulation; Innate defenses; Gonococcal antigens ID OUTER-MEMBRANE PROTEIN; FEMALE GENITAL-TRACT; TOXIN-B-SUBUNIT; EXPERIMENTAL GONOCOCCAL-INFECTION; SEXUALLY-TRANSMITTED-DISEASES; SYSTEMIC ANTIBODY-RESPONSES; SEROVAR-SPECIFIC IMMUNITY; NEISSERIA-GONORRHOEAE; PATHOGENIC NEISSERIA; INTRANASAL IMMUNIZATION AB Gonorrhea occurs at high incidence throughout the world and significantly impacts reproductive health and the spread of human immunodeficiency virus. Current control measures are inadequate and seriously threatened by the rapid emergence of antibiotic resistance. Progress on gonorrhea vaccines has been slow; however, recent advances justify significant effort in this area. Conserved vaccine antigens have been identified that elicit bactericidal antibodies and, or play key roles in pathogenesis that could be targeted by a vaccine-induced response. A murine genital tract infection model is available for systematic testing of antigens, immunization routes and adjuvants, and transgenic mice exist to relieve some host restrictions. Furthermore, mechanisms by which Neisseria gonorrhoeae avoids inducing a protective adaptive response are being elucidated using human cells and the mouse model. Induction of a Th1 response in mice clears infection and induces a memory response, which suggests Th1-inducing adjuvants may be key in vaccine-induced protection. Continued research in this area should include human testing and clinical studies to confirm or negate findings from experimental systems and to define protective host factors. (C) 2013 Published by Elsevier Ltd. C1 [Jerse, Ann E.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Bash, Margaret C.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20814 USA. [Russell, Michael W.] SUNY Buffalo, Witebsky Ctr Microbial Pathogenesis & Immunol, Dept Microbiol & Immunol, Buffalo, NY 14214 USA. RP Jerse, AE (reprint author), Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM annjerse@usuhs.edu; Margaret.Bash@fda.hhs.gov; russellm@buffalo.edu OI Russell, Michael/0000-0002-1303-4061 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [RO1-AI 42053, U19 AI31496, R21 AI074791]; John R. Oishei Foundation, Buffalo, New York FX Funding for this work was provided to A.E.J. by grants RO1-AI 42053 and U19 AI31496 and to M.W.R. by grant R21 AI074791 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. M.W.R. was also supported by the John R. Oishei Foundation, Buffalo, New York. We thank Marcia Hobbs and John Nyquist, M.S., C.M.I, F.A.M.I., for preparation of the figures and Freyja Lynn and Amanda DeRocco for helpful reading of the manuscript. NR 107 TC 21 Z9 23 U1 4 U2 28 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAR 20 PY 2014 VL 32 IS 14 SI SI BP 1579 EP 1587 DI 10.1016/j.vaccine.2013.08.067 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AE2HM UT WOS:000333793900010 PM 24016806 ER PT J AU Slaughter, SR Hearns-Stokes, R van der Vlugt, T Joffe, HV AF Slaughter, Shelley R. Hearns-Stokes, Rhonda van der Vlugt, Theresa Joffe, Hylton V. TI FDA Approval of Doxylamine-Pyridoxine Therapy for Use in Pregnancy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BIRTH-DEFECTS; BENDECTIN C1 [Slaughter, Shelley R.; Hearns-Stokes, Rhonda; van der Vlugt, Theresa; Joffe, Hylton V.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Slaughter, SR (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 5 TC 13 Z9 13 U1 1 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 20 PY 2014 VL 370 IS 12 BP 1081 EP 1083 DI 10.1056/NEJMp1316042 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AD2HA UT WOS:000333054000002 PM 24645939 ER PT J AU Chalbot, MCG Brown, J Chitranshi, P da Costa, GG Kavouras, IG AF Chalbot, Marie-Cecile G. Brown, Joeline Chitranshi, Priyanka da Costa, Goncalo Gamboa Kavouras, Ilias G. TI H-1-NMR characterization of water soluble compounds in size-segregated aerosols in an urban area SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 247th National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 16-20, 2014 CL Dallas, TX SP Amer Chem Soc C1 [Chalbot, Marie-Cecile G.; Brown, Joeline; Kavouras, Ilias G.] Univ Arkansas Med Sci, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA. [Chitranshi, Priyanka; da Costa, Goncalo Gamboa] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM mchalbot@uams.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 16 PY 2014 VL 247 MA 101-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8HZ UT WOS:000348457600320 ER PT J AU Forrey, C AF Forrey, Christopher TI Prediction and validation of diffusion coefficients in a model drug delivery system SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 247th National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 16-20, 2014 CL Dallas, TX SP Amer Chem Soc C1 [Forrey, Christopher] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20933 USA. EM eernst@comcast.net NR 0 TC 0 Z9 0 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 16 PY 2014 VL 247 MA 59-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8HZ UT WOS:000348457604044 ER PT J AU Zhang, HY Subburaj, K Johnson, DF Connell, B Skanchy, D AF Zhang, Huyi Subburaj, Kandasamy Johnson, Deborah F. Connell, Brian Skanchy, David TI Challenges in characterization of generic polymer drug substances SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 247th National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 16-20, 2014 CL Dallas, TX SP Amer Chem Soc C1 [Zhang, Huyi; Subburaj, Kandasamy; Johnson, Deborah F.; Connell, Brian; Skanchy, David] US FDA, Off Gener Drugs, Rockville, MD 20850 USA. EM huyi.zhang@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 16 PY 2014 VL 247 MA 292-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8HZ UT WOS:000348457604688 ER PT J AU Alusta, P Buzatu, D Tarasenko, O Wilkes, J AF Alusta, Pierre Buzatu, Dan Tarasenko, Olga Wilkes, Jon TI Distinction of Salmonella enterica subsp enterica serovar typhimurium strains through pattern recognition of weighted mass spectra SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 247th National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 16-20, 2014 CL Dallas, TX SP Amer Chem Soc C1 [Alusta, Pierre; Buzatu, Dan; Wilkes, Jon] Natl Ctr Toxicol Res, Syst Biol Div, Jefferson, AR 72079 USA. [Tarasenko, Olga] Univ Arkansas, Dept Biol, Little Rock, AR 72204 USA. EM pierre.alusta@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 16 PY 2014 VL 247 MA 34-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8HD UT WOS:000348455200035 ER PT J AU Baker, J AF Baker, Jeffrey TI Biosimilar pharmaceutical products in the United States: Foundations and frameworks SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 247th National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 16-20, 2014 CL Dallas, TX SP Amer Chem Soc C1 [Baker, Jeffrey] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Jeffrey.Baker@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 16 PY 2014 VL 247 MA BIOT-340 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8HD UT WOS:000348455201017 ER PT J AU Borodina, Y Callahan, L Switzer, F Hess, B Levin, R AF Borodina, Yulia Callahan, Larry Switzer, Frank Hess, Bill Levin, Randy TI FDA terminology for substances SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 247th National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 16-20, 2014 CL Dallas, TX SP Amer Chem Soc C1 [Borodina, Yulia; Callahan, Larry; Switzer, Frank; Hess, Bill; Levin, Randy] US FDA, Off Commissioner, Silver Spring, MD 20993 USA. EM yulia.borodina@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 16 PY 2014 VL 247 MA 4-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8HD UT WOS:000348455203598 ER PT J AU Gordonov, T Kim, E Zhou, YT Cheng, Y Ben-Yohav, H Ghodssi, R Rubloff, G Yin, JJ Payne, G Bentley, W AF Gordonov, Tanya Kim, Eunkyoung Zhou, Yuting Cheng, Yi Ben-Yohav, Hadar Ghodssi, Reza Rubloff, Gary Yin, Jun-Jie Payne, Gregory Bentley, William TI Electronic attenuation of biochemical signal generation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 247th National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 16-20, 2014 CL Dallas, TX SP Amer Chem Soc C1 [Gordonov, Tanya; Kim, Eunkyoung; Payne, Gregory; Bentley, William] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20740 USA. [Cheng, Yi; Ben-Yohav, Hadar; Ghodssi, Reza; Rubloff, Gary] Univ Maryland, Syst Res Inst, College Pk, MD 20740 USA. [Cheng, Yi; Rubloff, Gary] Univ Maryland, Dept Mat Sci & Engn, College Pk, MD 20740 USA. [Gordonov, Tanya; Kim, Eunkyoung; Payne, Gregory; Bentley, William] Univ Maryland, Inst Biosci & Biotechnol Res, College Pk, MD 20740 USA. [Ben-Yohav, Hadar; Ghodssi, Reza] Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20740 USA. [Zhou, Yuting; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhou, Yuting] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20740 USA. EM tanyag@umd.edu RI Rubloff, Gary/D-4142-2009 OI Rubloff, Gary/0000-0002-1901-3982 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 16 PY 2014 VL 247 MA BIOT-330 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8HD UT WOS:000348455201007 ER PT J AU Jenkins, SV Chen, JY Zhang, YB AF Jenkins, Samir V. Chen, Jingyi Zhang, Yongbin TI Detection of nanoparticle aggregation in complex, biological environments SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 247th National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 16-20, 2014 CL Dallas, TX SP Amer Chem Soc C1 [Jenkins, Samir V.; Chen, Jingyi] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. [Zhang, Yongbin] Natl Ctr Toxicol Res, NCTR ORA Nanotechnol Core Facil, Jefferson, AR 72079 USA. EM svjenkin@email.uark.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 16 PY 2014 VL 247 MA 316-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8HD UT WOS:000348455204067 ER PT J AU Willis, K Hart, M AF Willis, Kelsey Hart, Mark TI Determination of toxic shock syndrome toxin-1 and alpha toxin production in menstrual toxic shock syndrome (mTSS) clinical isolates of Staphylococcus aureus SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 247th National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 16-20, 2014 CL Dallas, TX SP Amer Chem Soc C1 [Willis, Kelsey] Ouachita Baptisit Univ, Dept Chem, Arkadelphia, AR 71998 USA. [Willis, Kelsey] Ouachita Baptisit Univ, Dept Biol, Arkadelphia, AR 71998 USA. [Hart, Mark] Natl Ctr Toxicol Res, Dept Microbiol, Jefferson, AR 72132 USA. [Hart, Mark] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. EM wil49661@obu.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 16 PY 2014 VL 247 MA 484-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA AZ8HD UT WOS:000348455202393 ER PT J AU Mansfield, EA AF Mansfield, Elizabeth A. TI FDA Perspective on Companion Diagnostics: An Evolving Paradigm SO CLINICAL CANCER RESEARCH LA English DT Article AB Therapeutic products are now being developed that target particular molecular lesions found in various types of cancers. The ability to correctly identify patients whose cancers have targetable lesions generally depends on a well-validated diagnostic test. Development and use of diagnostic tests together with therapies in clinical trials yields the information necessary to make a regulatory determination that both products are safe and effective, likely have clinical utility when used together, and reach the market for patient benefit. This model, called co-development, has been developed relatively recently, and is being put to use in numerous cancer therapeutic development programs. The U. S. Food and Drug Administration (FDA) has articulated a policy that requires the coapproval of a diagnostic with a therapeutic product when the diagnostic is essential to the safe and effective use of the therapeutic product. At the same time, FDA has implemented a number of processes to manage the model without slowing the approval of the co-developed products. New diagnostic technologies, together with a rapid uptick in interest in targeted drugs, will challenge the still-evolving regulatory paradigm, but will likely result in some simplified approaches presenting new challenges in determining safety and effectiveness, but all with the promise of greater benefit to patients with cancer. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." (C)2014 AACR. C1 US FDA, Silver Spring, MD 20993 USA. RP Mansfield, EA (reprint author), US FDA, 10903 New Hampshire Ave,WO 66-5676, Silver Spring, MD 20993 USA. EM Elizabeth.mansfield@fda.hhs.gov NR 6 TC 24 Z9 24 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2014 VL 20 IS 6 BP 1453 EP 1457 DI 10.1158/1078-0432.CCR-13-1954 PG 5 WC Oncology SC Oncology GA AE2ON UT WOS:000333812700008 PM 24634468 ER PT J AU Juraschek, SP McAdams-Demarco, M Miller, ER Gelber, AC Maynard, JW Pankow, JS Young, H Coresh, J Selvin, E AF Juraschek, Stephen P. McAdams-Demarco, Mara Miller, Edgar R. Gelber, Allan C. Maynard, Janet W. Pankow, James S. Young, Hunter Coresh, Josef Selvin, Elizabeth TI Temporal Relationship Between Uric Acid Concentration and Risk of Diabetes in a Community-based Study Population SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; diabetes mellitus; uric acid ID NUTRITION EXAMINATION SURVEY; CORONARY-HEART-DISEASE; 3RD NATIONAL-HEALTH; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; INSULIN-RESISTANCE; FASTING GLUCOSE; SERUM GLUCOSE; HYPERURICEMIA; PLASMA AB Some observational studies have identified elevated uric acid concentration as a risk factor for diabetes, while others have found an inverse relationship. We examined both the association of uric acid level with incident diabetes and the change in uric acid concentration after a diabetes diagnosis. We analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study and quantified the independent association between uric acid level and incident diabetes via Cox proportional hazards models. The association between duration of diabetes and change in uric acid level was examined via linear regression. Among 11,134 participants without diagnosed diabetes at baseline (1987-1989), there were 1,294 incident cases of diabetes during a median of 9 years of follow-up (1987-1998). Uric acid level was associated with diabetes even after adjustment for risk factors (per 1 mg/dL, hazard ratio = 1.18, 95% confidence interval: 1.13, 1.23), and the association remained significant after adjustment for fasting glucose and insulin levels. Among participants with diabetes (n = 1,510), every additional 5 years' duration of diabetes was associated with a 0.10-mg/dL (95% confidence interval: 0.04, 0.15) lower uric acid level after adjustment. We conclude that uric acid concentration rises prior to diagnosis of diabetes and then declines with diabetes duration. Future studies investigating uric acid as a risk factor for cardiovascular disease should adequately account for the impact and timing of diabetes development. C1 [Juraschek, Stephen P.; McAdams-Demarco, Mara; Miller, Edgar R.; Gelber, Allan C.; Young, Hunter; Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Juraschek, Stephen P.; McAdams-Demarco, Mara; Miller, Edgar R.; Gelber, Allan C.; Young, Hunter; Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. [Juraschek, Stephen P.; McAdams-Demarco, Mara; Miller, Edgar R.; Gelber, Allan C.; Young, Hunter; Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Juraschek, Stephen P.; McAdams-Demarco, Mara; Miller, Edgar R.; Gelber, Allan C.; Young, Hunter; Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21205 USA. [Maynard, Janet W.] US FDA, Silver Spring, MD USA. [Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Selvin, E (reprint author), Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, 2024 East Monument St,Suite 2-600, Baltimore, MD 21205 USA. EM lselvin@jhsph.edu OI McAdams-DeMarco, Mara/0000-0003-3013-925X; Pankow, James/0000-0001-7076-483X FU National Heart, Lung, and Blood Institute [HHSN268201 100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN 268201100010C, HHSN268201100011C, HHSN 268201100012C, T32HL007024] FX The Atherosclerosis Risk in Communities (ARIC) Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201 100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN 268201100010C, HHSN268201100011C, and HHSN 268201100012C). S.P.J. was supported by Cardiovascular Epidemiology Training Grant T32HL007024 from the National Heart, Lung, and Blood Institute. NR 38 TC 9 Z9 13 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2014 VL 179 IS 6 BP 684 EP 691 DI 10.1093/aje/kwt320 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AD4UP UT WOS:000333246800005 PM 24418684 ER PT J AU Sachdeva, A Singh, AK Sharma, SK AF Sachdeva, Amita Singh, Ajay K. Sharma, Shashi K. TI An electrochemiluminescence assay for the detection of bio threat agents in selected food matrices and in the screening of Clostridium botulinum outbreak strains associated with type A botulism SO JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE LA English DT Article DE bio threat agents; electrochemiluminescene; Bacillus anthracis; spores; staphylococcal enterotoxin B; Clostridium botulinum; botulinum neurotoxins; botulism ID STAPHYLOCOCCAL-ENTEROTOXIN-B; BACILLUS-ANTHRACIS SPORES; CHEMILUMINESCENCE ENZYME-IMMUNOASSAY; MONOCLONAL-ANTIBODIES; TOXIN-F; NEUROTOXIN; IDENTIFICATION; ELISA; GERMINATION; PRODUCTS AB BACKGROUNDSpecific screening methods for complex food matrices are needed that enable unambiguous and sensitive detection of bio threat agents (BTAs) such as Bacillus anthracis spores and microbial toxins (e.g. staphylococcal enterotoxin B (SEB) and clostridial botulinum neurotoxins (BoNTs)). The present study describes an image-based 96-well Meso Scale Discovery (MSD) electrochemiluminescence (ECL) assay for simultaneous detection of BTAs in dairy milk products. RESULTSThe limit of detection of this ECL assay is 40 pg mL(-1) for BoNT/A complex, 10 pg mL(-1) for SEB and 40000 CFU mL(-1) for Bacillus anthracis spores in dairy milk products. The ECL assay was successfully applied to screen type A Clostridium botulinum outbreak strains. CONCLUSIONThe results of the study indicate that this ECL assay is very sensitive, rapid (<6 h) and multiplex in nature. The ECL assay has potential for use as an in vitro screening method for BTAs over other comparable immunoassays. (c) 2013 Society of Chemical Industry C1 [Sachdeva, Amita; Singh, Ajay K.; Sharma, Shashi K.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Sharma, SK (reprint author), US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM shashi.sharma@fda.hhs.gov FU Department of Homeland Security through an Inter Agency Grant FX The authors thank Dr Eric W Brown for valuable discussions and advice. This work was supported by the Department of Homeland Security through an Inter Agency Grant. The views or opinions presented in this article are those of the authors and should not be construed as an official view of the US Food and Drug Administration. The authors declare that there are no conflicts of interest. The experiments comply with the current laws of the United States of America for ethical standards. NR 33 TC 3 Z9 3 U1 1 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-5142 EI 1097-0010 J9 J SCI FOOD AGR JI J. Sci. Food Agric. PD MAR 15 PY 2014 VL 94 IS 4 BP 707 EP 712 DI 10.1002/jsfa.6310 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA AA6ZX UT WOS:000331247900012 PM 23873138 ER PT J AU Connor, EM Smoyer, WE Davis, JM Zajicek, A Ulrich, L Purucker, M Hirschfeld, S AF Connor, Edward M. Smoyer, William E. Davis, Jonathan M. Zajicek, Anne Ulrich, Linda Purucker, Mary Hirschfeld, Steven TI Meeting the Demand for Pediatric Clinical Trials SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material AB High-quality, cost-ef ective pediatric clinical trials require a robust research and regulatory infrastructure and a properly trained workforce. C1 [Connor, Edward M.] George Washington Univ, Dept Pediat, Washington, DC 20010 USA. [Connor, Edward M.] George Washington Univ, Clin & Translat Sci Inst, Washington, DC 20010 USA. [Connor, Edward M.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20010 USA. [Smoyer, William E.] Ohio State Univ, Nationwide Childrens Hosp, Res Inst, Ctr Clin & Translat Res, Columbus, OH 43205 USA. [Smoyer, William E.] Ohio State Univ, Dept Pediat, Columbus, OH 43205 USA. [Davis, Jonathan M.] Tufts Med Ctr, Floating Hosp Children, Dept Pediat, Boston, MA 02111 USA. [Davis, Jonathan M.] Tufts Med Ctr, Floating Hosp Children, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Zajicek, Anne; Hirschfeld, Steven] Eunice Kennedy Shriver NICHD, Bethesda, MD 20892 USA. [Ulrich, Linda] US FDA, Off Orphan Prod Dev, Silver Spring, MD 20993 USA. [Purucker, Mary] NCATS, CTSA, Bethesda, MD 20892 USA. RP Connor, EM (reprint author), George Washington Univ, Dept Pediat, Washington, DC 20010 USA. EM econnor@childrensnational.org RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 FU NCATS NIH HHS [UL1 TR000073, UL1 TR000075, UL1 TR001070, UL1TR000073, UL1TR000075, UL1TR001070] NR 7 TC 6 Z9 6 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAR 12 PY 2014 VL 6 IS 227 AR 227fs11 DI 10.1126/scitranslmed.3008043 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AC6KD UT WOS:000332630500001 PM 24622511 ER PT J AU Han, J Fujisawa, T Husain, SR Puri, RK AF Han, Jing Fujisawa, Toshio Husain, Syed R. Puri, Raj K. TI Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma SO BMC CANCER LA English DT Article DE HNSCC (head & neck squamous cell carcinoma); Stem-like cells; CD24; CD44; Salivary gland malignant neoplasms ID CD24 EXPRESSION; ALDEHYDE DEHYDROGENASE; MARKER; RESISTANCE; LINES; IMMUNOPHENOTYPES; GEMCITABINE; METASTASIS AB Background: Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC). However, CD44 is widely expressed in most cells in HNSCC tumor samples and several cell lines tested. We previously identified a small population of CD24+/CD44+ cells in HNSCC. In this study, we examined whether this population of cells may represent CSC in HNSCC. Methods: CD24+/CD44+ cells from HNSCC cell lines were sorted by flow cytometry, and their phenotype was confirmed by qRT-PCR. Their self-renewal and differentiation properties, clonogenicity in collagen gels, and response to anticancer drugs were tested in vitro. The tumorigenicity potential of CD24+/CD44+ cells was tested in athymic nude mice in vivo. Results: Our results show that CD24+/CD44+ cells possessed stemness characteristics of self-renewal and differentiation. CD24+/CD44+ cells showed higher cell invasion in vitro and made higher number of colonies in collagen gels compared to CD24-/CD44+ HNSCC cells. In addition, the CD24+/CD44+ cells were more chemo-resistant to gemcitabine and cisplatin compared to CD24-/CD44+ cells. In vivo, CD24+/CD44+ cells showed a tendency to generate larger tumors in nude mice compared to CD24-/CD44+ cell population. Conclusion: Our study clearly demonstrates that a distinct small population of CD24+/CD44+ cells is present in HNSCC that shows stem cell-like properties. This distinct small population of cells should be further characterized and may provide an opportunity to target HNSCC CSC for therapy. C1 [Han, Jing; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Rm 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov NR 39 TC 22 Z9 22 U1 0 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 11 PY 2014 VL 14 AR 173 DI 10.1186/1471-2407-14-173 PG 11 WC Oncology SC Oncology GA AD7DF UT WOS:000333421100001 PM 24612587 ER PT J AU Parker, CH Morgan, CR Rand, KD Engen, JR Jorgenson, JW Stafford, DW AF Parker, Christine H. Morgan, Christopher R. Rand, Kasper D. Engen, John R. Jorgenson, James W. Stafford, Darrel W. TI A Conformational Investigation of Propeptide Binding to the Integral Membrane Protein gamma-Glutamyl Carboxylase Using Nanodisc Hydrogen Exchange Mass Spectrometry SO BIOCHEMISTRY LA English DT Article ID K-DEPENDENT CARBOXYLASE; PHOSPHOLIPID-BILAYER NANODISCS; COAGULATION-FACTOR DEFICIENCY; VITAMIN-K; HYDROGEN/DEUTERIUM EXCHANGE; CARBOXYGLUTAMIC ACID; ACTIVE-SITE; FACTOR-IX; DEUTERIUM EXCHANGE; TRANSITION-STATES AB Gamma (gamma)-glutamyl carboxylase (GGCX) is an integral membrane protein responsible for the post-translational catalytic conversion of select glutamic acid (Glu) residues to gamma-carboxy glutamic acid (Gla) in vitamin K-dependent (VKD.) proteins. Understanding the mechanism of carboxylation and the role of GGCX in the vitamin K cycle is of biological interest in the development of therapeutics for blood coagulation disorders. Historically, biophysical investigations and structural characterizations of GGCX have been limited due to complexities involving the availability of an appropriate model membrane system. In previous work, a hydrogen exchange mass spectrometry (HX MS) platform was developed to study the structural configuration of GGCX in a near-native nanodisc phospholipid environment. Here we have applied the nanodisc-HX MS approach to characterize specific domains of GGCX that exhibit structural rearrangements upon binding the high-affinity consensus propeptide (pCon; AVFLSREQANQVLQRRRR). pCon binding was shown to be specific for monomeric GGCX-nanodiscs and promoted enhanced structural stability to the nanodisc-integrated complex while maintaining catalytic activity in the presence of carboxylation co-substrates. Noteworthy modifications in HX of GGCX were prominently observed in GGCX peptides 491-507 and 395-401 upon pCon association, consistent with regions previously identified as sites for propeptide and glutamate binding. Several additional protein regions exhibited minor gains in solvent protection upon propeptide incorporation, providing evidence for a structural reorientation of the GGCX complex in association with VKD carboxylation. The results herein demonstrate that nanodisc-HX MS can be utilized to study molecular interactions of membrane-bound enzymes in the absence of a complete three-dimensional structure and to map dynamic rearrangements induced upon ligand binding. C1 [Parker, Christine H.; Jorgenson, James W.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Stafford, Darrel W.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Morgan, Christopher R.; Rand, Kasper D.; Engen, John R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. RP Parker, CH (reprint author), US FDA, CFSAN HFS 707,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Christine.Parker@fda.hhs.gov FU National Institutes of Health [GM101135, HL48318, HL06350]; Danish Council for Independent Research Natural Sciences [09-063876, 11-104058]; Waters Corporation FX These studies were supported by the National Institutes of Health (Grant GM101135 to J.R.E. and Grants HL48318 and HL06350 to D.W.S.), the Danish Council for Independent Research Natural Sciences (Grants 09-063876 and 11-104058 to K.D.R.), and Waters Corporation (J.W.J and J.R.E.). NR 65 TC 21 Z9 21 U1 1 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 11 PY 2014 VL 53 IS 9 BP 1511 EP 1520 DI 10.1021/bi401536m PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AD0GX UT WOS:000332913600013 PM 24512177 ER PT J AU Paseiro-Cerrato, R Noonan, GO Begley, TH AF Paseiro-Cerrato, R. Noonan, G. O. Begley, T. H. TI Development of a rapid screening method to determine primary aromatic amines in kitchen utensils using direct analysis in real time mass spectrometry (DART-MS) SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article; Proceedings Paper CT 5th ILSI International Symposium on Food Packaging CY NOV 14-16, 2012 CL Berlin, GERMANY DE primary aromatic amines; direct analysis in real time (DART); screening method; UPLC-MS; MS; kitchen utensils ID FOOD-CONTACT MATERIALS; GAS-CHROMATOGRAPHY; AMBIENT CONDITIONS; COOKING UTENSILS; FINGER-PAINTS; ION-SOURCE; IONIZATION; IDENTIFICATION; PRODUCTS; MIGRATION AB Primary aromatic amines (PAAs) are a group of substances with undesirable health effects, that are used in a variety of commercial products. Several recent studies, using a number of screening and confirmatory methods, have reported the migration of PAAs from some kitchen utensils into acetic acid 3% (w/v). Many of these methods require significant sample preparation, therefore the aim of this work was to determine if direct analysis in real time mass spectrometry (DART-MS) could be utilised as a rapid screening tool for the determination of PAAs in kitchen utensils. DART-MS results from direct analysis of the utensil have been compared with results of PAA migration by ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The UPLC-MS/MS method had excellent linearity, appropriate sensitivity (LOD1.5 mu gL(-1); LOQ4.5 mu gL(-1)), repeatability from 2.4 to 13.2% and acceptable recoveries. DART-MS results were in good agreement with UPLC-MS/MS data, with 100% of non-compliant (PAA positive) samples successfully identified by DART-MS. C1 [Paseiro-Cerrato, R.] Univ Santiago de Compostela, Fac Pharm, Dept Analyt Chem Nutr & Food Sci, E-15782 Santiago De Compostela, Spain. [Noonan, G. O.; Begley, T. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Noonan, GO (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Gregory.Noonan@fda.hhs.gov RI Paseiro Losada, Perfecto/B-6882-2009 FU Ministerio de Ciencia e Innovacion [BES-2009-023016] FX This work was supported by the "Ministerio de Ciencia e Innovacion" through the Predoctoral fellowship FPI (ref. BES-2009-023016) awarded to R. Paseiro-Cerrato. NR 32 TC 5 Z9 5 U1 1 U2 22 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1944-0049 EI 1944-0057 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PD MAR 4 PY 2014 VL 31 IS 3 SI SI BP 537 EP 545 DI 10.1080/19440049.2013.867366 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA AE3LR UT WOS:000333878500015 PM 24256323 ER PT J AU Wang, X Tan, JY Zoueva, O Zhao, JQ Ye, ZP Hewlett, I AF Wang, Xue Tan, Jiying Zoueva, Olga Zhao, Jiangqin Ye, Zhiping Hewlett, Indira TI Novel pandemic influenza A (H1N1) virus infection modulates apoptotic pathways that impact its replication in A549 cells SO MICROBES AND INFECTION LA English DT Article DE Pandemic influenza A (H1N1) virus; Apoptosis; Bax; Fas; MAPK; Viral replication ID AIRWAY EPITHELIAL-CELLS; VIRAL-REPLICATION; IMMUNE-RESPONSES; UP-REGULATION; P53; ACTIVATION; INDUCTION; DEATH; PROPAGATION; EXPRESSION AB It is not well-known whether apoptosis signaling affects influenza virus infection and reproduction in human lung epithelial cells. Using A549 cell line, we studied the relationship of some apoptosis-associated molecules with novel pandemic influenza A (H1N1) virus, A/California/04/2009. Infected cells displayed upregulated Fas ligand, activated FADD and caspase-8, and downregulated FLIP in the extrinsic apoptotic pathway. p53 expression increased and Bcl-X-L, expression decreased in the intrinsic pathway. Expression of pre-apoptotic molecules (FasL, FADD, and p53) increased virus replication, while inhibition of activity of FADD, caspase-8 and caspase-3, and expression of anti-apoptotic proteins (FLIP and Bcl-X-L) decreased virus replication. p38, ERK and INK from MAPK pathways were activated in infected cells, and inhibition with their inhibitors diminished virus replication. In the p38 superfamily, p38 alpha expression increased viral RNA production, while expression of p38 beta and p38 gamma decreased. These data indicated that influenza virus induces apoptotic signaling pathways, which benefit virus replication. Published by Elsevier Masson SAS on behalf of Institut Pasteur. C1 [Wang, Xue; Tan, Jiying; Zhao, Jiangqin; Hewlett, Indira] Div Emerging & Transfus Transmitted Dis, Mol Virol Lab, Bethesda, MD 20892 USA. [Zoueva, Olga; Ye, Zhiping] Ctr Biol Evaluat & Res Food & Drug Adm, Div Viral Prod, Bethesda, MD 20892 USA. RP Wang, X (reprint author), CBER FDA, Mol Virol Lab, Bldg 29B,Rm 4NN22,8800 Rockville Pike, Bethesda, MD 20892 USA. EM xue.wang@fda.hhs.gov NR 42 TC 8 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 EI 1769-714X J9 MICROBES INFECT JI Microbes Infect. PD MAR PY 2014 VL 16 IS 3 BP 178 EP 186 DI 10.1016/j.micinf.2013.11.003 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AY9IU UT WOS:000347864600002 PM 24262752 ER PT J AU Yamazaki, A Marini-Bettolo, C Kodera, Y Badano, A AF Yamazaki, Asumi Marini-Bettolo, Cecilia Kodera, Yoshie Badano, Aldo TI Sharpness and noise characteristics of a half-mirror stereoscopic display SO JOURNAL OF THE SOCIETY FOR INFORMATION DISPLAY LA English DT Article DE stereoscopic display; sharpness; noise; crosstalk ID BREAST-CANCER; MAMMOGRAPHY; PERFORMANCE AB Stereoscopic displays are becoming popular in entertainment and industrial applications. We characterize the spatial resolution and noise properties of a stereoscopic display with a half-mirror and passive polarizing glasses. The upper display images reflected off the mirror have slightly degraded sharpness and reduced high spatial-frequency noise resulting in modulation transfer functions (MTFs) of 0.59 and 0.50 at the Nyquist frequency with corresponding noise power spectra (NPS) values of 4.79x10(-6) and 5.17x10(-6)mm(2) at 10mm(-1) in the horizontal and vertical directions. These results are compared to the characteristics of the individual displays with MTF values of 0.64 and 0.53 and NPS values of 6.24x10(-6) and 5.87x10(-6)mm(2). The polarizing glasses cause minimal reduction in sharpness and high-frequency noise. The MTFs in the upper images observed with glasses are decreased to 0.54 and 0.47, while the NPS are decreased to 2.86x10(-6) and 2.01x10(-6)mm(2). When both displays are turned on and using the mirror and glasses, the observed luminance for each eye is increased from the luminance of the individual displays owing to crosstalk. We find that sharpness and noise are not affected by the interaction between the displays at the particular geometry tested in this study. C1 [Yamazaki, Asumi; Marini-Bettolo, Cecilia; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Kodera, Yoshie] Nagoya Univ, Grad Sch Med, Nagoya, Aichi 4618673, Japan. RP Yamazaki, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU US DOE; US FDA FX A. Y. and C. M.-B. acknowledge funding by appointments to the Research Participation Program at the CDRH administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US DOE and the US FDA. The mention of commercial products herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. This is a contribution of the FDA and is not subject to copyright. NR 17 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1071-0922 EI 1938-3657 J9 J SOC INF DISPLAY JI J. Soc. Inf. Disp. PD MAR PY 2014 VL 22 IS 3 BP 170 EP 176 DI 10.1002/jsid.232 PG 7 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Optics; Physics, Applied SC Engineering; Materials Science; Optics; Physics GA AU4QI UT WOS:000345596400006 ER PT J AU Simonetti, A Forshee, RA Anderson, SA Walderhaug, M AF Simonetti, Arianna Forshee, Richard A. Anderson, Steven A. Walderhaug, Mark TI A stock-and-flow simulation model of the US blood supply SO TRANSFUSION LA English DT Article ID MANAGEMENT; AVAILABILITY; ALLOCATION; INFLUENZA AB BACKGROUND: Lack of reporting requirements for the amount of blood stored in blood banks and hospitals poses challenges to effectively monitor the US blood supply. Effective strategies to minimize collection and donation disruptions in the supply require an understanding of the daily amount of blood available in the system. STUDY DESIGN AND METHODS: A stock-and-flow simulation model of the US blood supply was developed to obtain estimates of the daily on-hand availability of blood, with uncertainty and by ABO/Rh type. The model simulated potential impact on supply of using different blood management practices for transfusion: first in-first out (FIFO), using the oldest stored red blood cell units first; non-FIFO likely oldest, preferentially selecting older blood; and non-FIFO likely newest, preferentially selecting younger blood. RESULTS: Simulation results showed higher estimates of the steady-state of the blood supply level for FIFO (1,630,000 units, 95% prediction interval [PI] 1,610,000-1,650,000) than non-FIFO scenarios (likely oldest, 1,530,000 units, 95% PI 1,500,000-1,550,000; and likely newest, 1,190,000 units, 95% PI 1,160,000-1,220,000), either for overall blood or by blood types. CONCLUSION: To our knowledge, this model represents a first attempt to evaluate the impact of different blood management practices on daily availability and distribution of blood in the US blood supply. The average storage time before blood is being issued was influenced by blood management practices, for preferences of blood that is younger and also that use specific blood types. The model also suggests which practice could best approximate the current blood management system and may serve as useful tool for blood management. C1 [Simonetti, Arianna; Forshee, Richard A.; Anderson, Steven A.; Walderhaug, Mark] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Simonetti, A (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM-210 WOC 1,Suite 316N, Rockville, MD 20852 USA. EM Arianna.Simonetti@fda.hhs.gov FU HHS/BARDA [224-08-1088]; Research Participation Program at the Center for Biologics Evaluation and Research FX This research was supported in the form of Grant 224-08-1088 from HHS/BARDA. This project was supported in part by the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. NR 25 TC 1 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAR PY 2014 VL 54 IS 3 SI SI BP 828 EP 838 DI 10.1111/trf.12392 PN 2 PG 11 WC Hematology SC Hematology GA AM9GI UT WOS:000340188500014 PM 23992403 ER PT J AU Ness, GL Sheehan, AH Snyder, ME AF Ness, Genevieve Lynn Sheehan, Amy Heck Snyder, Margie E. TI Graduating student pharmacists' perspectives on e-professionalism and social media: Qualitative findings SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE Social media; student pharmacists; e-professionalism; social networking; qualitative analysis ID FACEBOOK; EDUCATION AB Objective: To characterize students' views and opinions of professionalism on popular social media sites and compare responses about social media behavior among students in different groups. Design: Cross-sectional survey. Setting: Four colleges of pharmacy in midwestern United States. Participants: 516 graduating student pharmacists. Interventions: Online survey with open-ended questions. Main outcome measures: Qualitative analysis of responses and themes. Results: A total of 212 student pharmacists completed surveys (41% response rate). Mean (+/- SD) age was 25.2 +/- 4.6 years, and 72% of respondents were women. Major overarching themes identified in the qualitative analysis were separation of personal and professional lives, how accountability for actions should vary by severity, and the extent of representation of the students' character on social media. Conclusion: Identified themes provided important insights into the ways in which student pharmacists view social media and use this widely accessible means of personal communication. C1 [Ness, Genevieve Lynn] Christy Houston Fdn Drug Informat Ctr, Nashville, TN USA. [Ness, Genevieve Lynn] Belmont Univ, Coll Pharm, Nashville, TN 37212 USA. [Ness, Genevieve Lynn] Purdue Univ, W Lafayette, IN 47907 USA. [Ness, Genevieve Lynn] Eli Lilly & Co, Indianapolis, IN USA. [Ness, Genevieve Lynn] US FDA, Rockville, MD 20857 USA. [Snyder, Margie E.] Purdue Univ, Coll Pharm, Indianapolis, IN USA. RP Ness, GL (reprint author), Belmont Univ, Coll Pharm, Nashville, TN 37212 USA. EM gness2011@gmail.com FU National Institutes of Health [KL2RR025760]; Agency for Healthcare Research and Quality [K08HS022119]; Gloria Niemeyer Francke Grant Program from the Department of Pharmacy Practice, Purdue University College of Pharmacy FX Funding: Dr. Snyder's effort was supported in part by KL2RR025760 (A. Shekhar, principal investigator), National Institutes of Health, and a portion of Dr. Snyder's effort was supported by grant number K08HS022119 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. Dr. Ness and Dr. Sheehan's efforts were supported in part by the Gloria Niemeyer Francke Grant Program from the Department of Pharmacy Practice, Purdue University College of Pharmacy. NR 15 TC 0 Z9 0 U1 1 U2 6 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 EI 1544-3450 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD MAR-APR PY 2014 VL 54 IS 2 BP 138 EP U323 DI 10.1331/JAPhA.2014.13188 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK4YH UT WOS:000338430000005 PM 24632929 ER PT J AU Gonzalez, Y Aryal, B Chehab, L Rao, VA AF Gonzalez, Yanira Aryal, Baikuntha Chehab, Leena Rao, V. Ashutosh TI Atg7-and Keap1-dependent autophagy protects breast cancer cell lines against mitoquinone-induced oxidative stress SO ONCOTARGET LA English DT Article DE autophagy; reactive oxygen species; mitoquinone; breast cancer ID TRANSCRIPTION FACTOR NRF2; BECLIN 1-INDEPENDENT AUTOPHAGY; REACTIVE OXYGEN; SELECTIVE AUTOPHAGY; KEAP1-NRF2 PATHWAY; CARCINOMA CELLS; P62; DEGRADATION; MITOCHONDRIA; ANTIOXIDANT AB The interplay between oxidative stress and autophagy is critical for determining the fate of cancer cells exposed to redox-active and cytotoxic chemotherapeutic agents. Mitoquinone (MitoQ), a mitochondrially-targeted redox-active ubiquinone conjugate, selectively kills breast cancer cells over healthy mammary epithelial cells. We reported previously that MitoQ, although a derivative of the antioxidant ubiquinone, can generate excess ROS and trigger the Keap1-Nrf2 antioxidant response in the MDA-MB-231 cell line. Following MitoQ treatment, a greater number of cells underwent autophagy than apoptosis. However, the relationship between MitoQ-induced oxidative stress and autophagy as a primary cellular response was unclear. In this report, we demonstrate that MitoQ induces autophagy related gene 7 (Atg7)-dependent, yet Beclin-1-independent, autophagy marked by an increase in LC3-II. Both the ATG7-deficient human MDA-MB-231 cells and Atg7-knockout mouse embryonic fibroblasts exhibited lower levels of autophagy following MitoQ treatment than their respective wild-type counterparts. Increased apoptosis was confirmed in these autophagy-deficient isogenic cell line pairs, indicating that autophagy was attempted for survival in wild type cell lines. Furthermore, we observed higher levels of ROS in Atg7-deficient cells, as measured by hydroethidine oxidation. In Atg7-deficient cells, redox-sensitive Keap1 degradation was decreased, suggesting autophagy- and Atg7-dependent degradation of Keap1. Conversely, downregulation of Keap1 decreased autophagy levels, increased Nrf2 activation, upregulated cytoprotective antioxidant gene expression, and caused accumulation of p62, suggesting a feedback loop between ROS-regulated Keap1-Nrf2 and Atg7-regulated autophagy. Our data indicate that excessive ROS causes the upregulation of autophagy, and autophagy acts as an antioxidant feedback response triggered by cytotoxic levels of MitoQ. C1 [Gonzalez, Yanira; Aryal, Baikuntha; Chehab, Leena; Rao, V. Ashutosh] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Rao, VA (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM ashutosh.rao@fda.hhs.gov FU FDA Critical Path Initiative; Center for Drug Evaluation and Research FX Atg7+/+ and Atg7-/- MEF cells were generously provided by Dr. Masaaki Komatsu (Tokyo Metropolitan Institute). The authors acknowledge research support from the FDA Critical Path Initiative. This project was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. We thank Drs. Jacek Zielonka, Joy Joseph, Balaraman Kalyanaraman, and the Free Radical Research Center (Medical College of Wisconsin) for assistance with HPLC studies. We also thank Dr. Melanie Simpson (NCI) and Mr. Elliot Rosen (FDA) for critical reading of the manuscript. NR 43 TC 12 Z9 14 U1 0 U2 12 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAR PY 2014 VL 5 IS 6 BP 1526 EP 1537 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6EO UT WOS:000336964000011 PM 24681637 ER PT J AU Crawford, K Mazzola, E Khachik, F AF Crawford, Kristine Mazzola, Eugene Khachik, Frederick TI Total Synthesis of 1,2,5,6-Tetrahydro-2,6-cyclo-gamma-carotene-1,5-diol, an Oxidation Product of gamma-Carotene SO SYNTHESIS-STUTTGART LA English DT Article DE hydroxycarotenoids; Wittig reaction; gamma-carotene oxidation; carotenoid precursors; epoxide cyclization ID TECHNICAL PROCEDURES; DIETARY CAROTENOIDS; TOMATO JUICE; HUMAN SERUM; LYCOPENE; METABOLITES; IDENTIFICATION; (3R,3'R,6'R)-LUTEIN; (3R,3'R)-ZEAXANTHIN; 6-OXO-ISOPHORONE AB 1,2,5,6-Tetrahydro-2,6-cyclo-gamma-carotene-1,5-diol, an oxidation product of the pro-vitamin A food carotenoid.-carotene, was synthesized by a C-15 + C-10 + C-15 double Wittig coupling strategy. The total synthesis involved a key C15-dihydroxyaldehyde synthon derived from (E/Z)-citral, a protected C-10-Wittig salt, and (beta-ionylideneethyl) triphenylphosphonium chloride (C-15-Wittig salt). This synthetic route provides novel access to an oxidation product of gamma-carotene that could be potentially formed in humans or biological systems as a consequence of metabolic oxidation. C1 [Crawford, Kristine; Mazzola, Eugene; Khachik, Frederick] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Crawford, Kristine] DSM Nutr Prod, Columbia, MD 21045 USA. [Mazzola, Eugene] US FDA, JIFSAN, College Pk, MD 20742 USA. RP Khachik, F (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM khachik@umd.edu FU DSM Nutritional Products (Columbia, Maryland, USA) FX The authors would like to thank DSM Nutritional Products (Columbia, Maryland, USA) for funding support. NR 34 TC 3 Z9 3 U1 0 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0039-7881 EI 1437-210X J9 SYNTHESIS-STUTTGART JI Synthesis PD MAR PY 2014 VL 46 IS 5 BP 635 EP 645 DI 10.1055/s-0033-1340555 PG 11 WC Chemistry, Organic SC Chemistry GA AI4MB UT WOS:000336838400009 ER PT J AU Madhavarao, CN Agarabi, CD Wong, L Muller-Loennies, S Braulke, T Khan, M Anderson, H Johnson, GR AF Madhavarao, Chikkathur N. Agarabi, Cyrus D. Wong, Lily Mueller-Loennies, Sven Braulke, Thomas Khan, Mansoor Anderson, Howard Johnson, Gibbes R. TI Evaluation of butyrate-induced production of a mannose-6-phosphorylated therapeutic enzyme using parallel bioreactors SO BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY LA English DT Article DE lysosomal storage diseases; enzyme replacement therapies; mannose-6-phosphate; enzymes; bioreactors; capillary electrophoresis ID BETA-GLUCURONIDASE DEFICIENCY; LYSOSOMAL STORAGE DISEASES; HAMSTER OVARY CELLS; CHO-CELLS; MAMMALIAN-CELLS; HYPOTHERMIC GROWTH; CULTURE-CONDITIONS; PROTEIN-PRODUCTION; SODIUM-BUTYRATE; MUCOPOLYSACCHARIDOSIS AB Bioreactor process changes can have a profound effect on the yield and quality of biotechnology products. Mannose-6-phosphate (M6P) glycan content and the enzymatic catalytic kinetic parameters are critical quality attributes (CQAs) of many therapeutic enzymes used to treat lysosomal storage diseases (LSDs). Here, we have evaluated the effect of adding butyrate to bioreactor production cultures of human recombinant -glucuronidase produced from CHO-K1 cells, with an emphasis on CQAs. The -glucuronidase produced in parallel bioreactors was quantified by capillary electrophoresis, the catalytic kinetic parameters were measured using steady-state analysis, and mannose-6-phosphorylation status was assessed using an M6P-specific single-chain antibody fragment. Using this approach, we found that butyrate treatment increased -glucuronidase production up to approximately threefold without significantly affecting the catalytic properties of the enzyme. However, M6P content in -glucuronidase was inversely correlated with the increased enzyme production induced by butyrate treatment. This assessment demonstrated that although butyrate dramatically increased -glucuronidase production in bioreactors, it adversely impacted the mannose-6-phosphorylation of this LSD therapeutic enzyme. This strategy may have utility in evaluating manufacturing process changes to improve therapeutic enzyme yields and CQAs. C1 [Madhavarao, Chikkathur N.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Agarabi, Cyrus D.; Khan, Mansoor] US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Wong, Lily; Anderson, Howard; Johnson, Gibbes R.] US FDA, Div Therapeut Prot, CDER, Bethesda, MD 20892 USA. [Mueller-Loennies, Sven] Leibniz Ctr Med & Biosci, Div Med & Biochem Microbiol, Res Ctr Borstel, Borstel, Germany. [Braulke, Thomas] Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, Dept Biochem, Hamburg, Germany. RP Johnson, GR (reprint author), US FDA, Div Therapeut Prot, CDER, Bldg 29A,Room 3B-16,HFD 122,29 Lincoln Dr, Bethesda, MD 20892 USA. EM gibbes.johnson@fda.hhs.gov FU CDER/US FDA FX This work was supported in part by a Critical Path grant from CDER/US FDA to G. R. Johnson. The authors thank Claudia Chen for the adaptation of parent CHO-K1 cells to suspension growth and Kurt Brorson for critical reading and comments on the manuscript. T. Braulke and S. Muller-Loennies hold a patent on the single-chain antibody fragment for the detection of M6P-containing proteins (International Patent no. PTC/EP2009/060224 and U.S./PTC Application no. 13/057,844). NR 32 TC 1 Z9 1 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-4513 EI 1470-8744 J9 BIOTECHNOL APPL BIOC JI Biotechnol. Appl. Biochem. PD MAR PY 2014 VL 61 IS 2 BP 184 EP 192 DI 10.1002/bab.1151 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA AF3KG UT WOS:000334610400013 PM 24033810 ER PT J AU Samuels-Reid, JH Blake, ED AF Samuels-Reid, Joy H. Blake, Erica D. TI Pediatric medical devices: a look at significant US legislation to address unmet needs SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Article DE FDA; medical devices; pediatric; pediatric population; pediatric subpopulation; unmet needs; US legislation AB There are many barriers to the availability of medical devices intended for the pediatric population causing healthcare providers to use creative measures to address pediatric unmet device needs. The USA has taken significant legislative measures to spur medical device development and address the unmet needs in all pediatric subpopulations. For example, the Medical Device User Fee and Modernization Act of 2002 amended the Federal Food Drug and Cosmetic Act by adding new provisions intended to promote the development of safe and effective pediatric devices, and to protect the pediatric population during clinical trials. In 2004, the Medical Devices Technical Corrections Act was added to address potential difficulties in bringing pediatric devices to the market. Further, the Pediatric Medical Device Safety and Improvement Act of 2007 and the Food and Drug Administration Amendments Act of 2007 provided the FDA significant new responsibilities and authorities regarding pediatric use. C1 [Samuels-Reid, Joy H.; Blake, Erica D.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Samuels-Reid, JH (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave WO 66-2608, Silver Spring, MD 20993 USA. EM joy.samuels-reid@fda.hhs.gov NR 7 TC 0 Z9 0 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 EI 1745-2422 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD MAR PY 2014 VL 11 IS 2 BP 169 EP 174 DI 10.1586/17434440.2014.864234 PG 6 WC Engineering, Biomedical SC Engineering GA AG3MS UT WOS:000335324000008 PM 24387679 ER PT J AU Pinnow, E Herz, N Loyo-Berrios, N Tarver, M AF Pinnow, Ellen Herz, Naomi Loyo-Berrios, Nilsa Tarver, Michelle TI Enrollment and Monitoring of Women in Post-Approval Studies for Medical Devices Mandated by the Food and Drug Administration SO JOURNAL OF WOMENS HEALTH LA English DT Article ID CARDIAC RESYNCHRONIZATION THERAPY; TOTAL KNEE ARTHROPLASTY; GENDER-DIFFERENCES; FAILURE; RISK AB Background: Disease presentation, prevalence, and treatment effects vary by sex, thus it is important to ensure adequate participation of both sexes in medical device post-approval studies (PAS). Methods: The goals of this study were to determine the participation rate of women in PAS mandated by the Food and Drug Administration (FDA) and if participation varied by clinical area. The study also evaluated the frequency in which enrollment by sex is reported by applicant reports and FDA reviews, as well as the frequency in which final study reports analyze whether outcomes differ by sex. Results: Of 89 studies with enrollment completed, data on sex of participants were available in 93% of submitted reports, while data on enrollment by sex was evaluated and noted in 43% of FDA review memos. Study participation varied by clinical area, with female participation ranging from 32% in cardiovascular PAS to 90% in PAS for reconstructive devices. Of 53 completed studies, data on enrollment by sex was provided in 49 of the final reports. Of these 14% included a multivariate analysis that included sex as a covariate and 4% included a subgroup analysis for female participants. Conclusions: Data on sex was not routinely assessed in FDA reviews. Based on these findings, FDA implemented new procedures to ensure participation by sex is evaluated in PAS reviews. FDA will continue working with applicants to develop PAS that enroll and retain proportions of women consistent with the sex-specific prevalence for the disease or condition the device is used to treat. C1 [Pinnow, Ellen; Herz, Naomi; Loyo-Berrios, Nilsa; Tarver, Michelle] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Pinnow, E (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ellen.pinnow@fda.hhs.gov NR 22 TC 6 Z9 6 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD MAR 1 PY 2014 VL 23 IS 3 BP 218 EP 223 DI 10.1089/jwh.2013.4343 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AC4BQ UT WOS:000332466000006 PM 24405314 ER PT J AU Cooley, MB Quinones, B Oryang, D Mandrell, RE Gorski, L AF Cooley, Michael B. Quinones, Beatriz Oryang, David Mandrell, Robert E. Gorski, Lisa TI Prevalence of shiga toxin producing Escherichia coli Salmonella enterica, and Listeria monocytogenes at public access watershed sites in a California Central Coast agricultural region SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY LA English DT Article DE STEC O157:57; STEC non-O157; Salmonella; Listeria monocytogenes; watersheds; agriculture; leafy-vegetable production; prevalence ID UNITED-STATES; MOLECULAR CHARACTERIZATION; SURFACE WATERS; WILD BIRDS; FOOD; ENVIRONMENT; DIVERSITY; OUTBREAKS; O157-H7; VIRULENCE AB Produce contaminated with enteric pathogens is a major source of foodborne illness in the United States. Lakes, streams, rivers, and ponds were sampled with Moore swabs bi-monthly for over 2 years at 30 locations in the vicinity of a leafy green growing region on the Central California Coast and screened for Shiga toxin producing Escherichia coli (STEC), Salmonella enterica, and Listeria monocytogenes to evaluate the prevalence and persistence of pathogen subtypes. The prevalence of STEC from 1386 samples was 11%; 110 samples (8%) contained E. coli O157:H7 with the highest prevalence occurring close to cattle operations. Non-O157 STEC isolates represented major clinical O-types and 57% contained both shiga toxin types 1 and 2 and intimin. Multiple Locus Variable Number Tandem Repeat Analysis of STEC isolates indicated prevalent strains during the period of study. Notably, Salmonella was present at high levels throughout the sampling region with 65% prevalence in 1405 samples resulting in 996 isolates with slightly lower prevalence in late autumn. There were 2, 8, and 14 sites that were Salmonella-positive over 90, 80, and 70% of the time, respectively. The serotypes identified most often were 6,8:d:-, Typhimurium, and Give. Interestingly, analysis by Pulsed Field Gel Electrophoresis indicated persistence and transport of pulsotypes in the region over several years. In this original study of L. monocytogenes in the region prevalence was 43% of 1405 samples resulting in 635 individual isolates. Over 85% of the isolates belonged to serotype 4b with serotypes 1/2a, 1/2b, 3a, 4d with 4e representing the rest, and there were 12 and 2 sites that were positive over 50 and 80% of the time, respectively. Although surface water is not directly used for irrigation in this region, transport to the produce can occur by other means. This environmental survey assesses initial contamination levels toward an understanding of transport leading to produce recalls or outbreaks. C1 [Cooley, Michael B.; Quinones, Beatriz; Mandrell, Robert E.; Gorski, Lisa] Agr Res Serv, Produce Safety & Microbiol Res Unit, USDA, Albany, CA 94710 USA. [Oryang, David] US FDA, Div Risk Anal, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Gorski, L (reprint author), Agr Res Serv, Produce Safety & Microbiol Res Unit, USDA, 800 Buchanan St, Albany, CA 94710 USA. EM lisa.gorski@ars.usda.gov FU Agricultural Research Service CRIS project [5325-42000-046-00D]; Food and Drug Administration [224-11-2044] FX The authors would like to thank D. Carychao, A. Liang, K. Nguyen, S. Walker, and J. Govoni for technical assistance. This work was supported by funds from Agricultural Research Service CRIS project 5325-42000-046-00D and grant #224-11-2044 from the Food and Drug Administration. NR 64 TC 20 Z9 20 U1 2 U2 34 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 2235-2988 J9 FRONT CELL INFECT MI JI Front. Cell. Infect. Microbiol. PD MAR PY 2014 VL 4 AR 30 DI 10.3389/fcimb.2014.00030 PG 13 WC Immunology; Microbiology SC Immunology; Microbiology GA AH4TC UT WOS:000336120000007 PM 24624367 ER PT J AU Simhadri, VL Hamasaki-Katagiri, N Tseng, SC Bentley, AA Zichel, R Hershko, AY Komar, AA Kimchi-Sarfaty, C AF Simhadri, V. L. Hamasaki-Katagiri, N. Tseng, S. C. Bentley, A. A. Zichel, R. Hershko, A. Y. Komar, A. A. Kimchi-Sarfaty, C. TI Factor IX oligomerization underlies reduced activity upon disruption of physiological conditions SO HAEMOPHILIA LA English DT Article ID COAGULATION-FACTOR-XI; BLOOD-COAGULATION; SERUM-ALBUMIN; HEMOPHILIA-B; PROTEIN-S; DIMERIZATION; PROTHROMBIN; ACTIVATION; APPLE-4; DOMAIN C1 [Simhadri, V. L.; Hamasaki-Katagiri, N.; Tseng, S. C.; Zichel, R.; Kimchi-Sarfaty, C.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Bentley, A. A.; Komar, A. A.] Cleveland State Univ, Dept Biol Geol & Environm Sci, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA. [Hershko, A. Y.] Meir Med Ctr, Dept Med, Kefar Sava, Israel. RP Kimchi-Sarfaty, C (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM a.komar@csuohio.edu; chava.kimchi-sarfaty@fda.hhs.gov FU Laboratory of Hemostasis; Center for Biologics Evaluation and Research; American Heart Association [13GRNT17070025] FX This study was supported by funds from the Laboratory of Hemostasis, Center for Biologics Evaluation and Research (CK-S) and The American Heart Association (grant 13GRNT17070025 to A.A.K.). We thank Dr. Zuben Sauna for fruitful discussions. Our contributions are an informal communication and represent our own best judgement. These comments do not bind or obligate FDA. NR 26 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 EI 1365-2516 J9 HAEMOPHILIA JI Haemophilia PD MAR PY 2014 VL 20 IS 2 BP E157 EP E163 PG 7 WC Hematology SC Hematology GA AB0CO UT WOS:000331459600008 PM 24417758 ER PT J AU De Pascalis, R Chou, AY Ryden, P Kennett, NJ Sjostedt, A Elkins, KL AF De Pascalis, Roberto Chou, Alicia Y. Ryden, Patrik Kennett, Nikki J. Sjostedt, Anders Elkins, Karen L. TI Models Derived from In Vitro Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the Francisella tularensis Live Vaccine Strain (LVS) SO MBIO LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; PROTECTIVE IMMUNITY; BCG VACCINE; TULAREMIA; CELLS; INFECTION; CORRELATE; MICE; INTERFERON; PREVENTION AB Currently, there are no licensed vaccines and no correlates of protection against Francisella tularensis, which causes tularemia. We recently demonstrated that measuring in vitro control of intramacrophage bacterial growth by murine F. tularensis-immune splenocytes, as well as transcriptional analyses, discriminated Francisella vaccines of different efficacies. Further, we identified potential correlates of protection against systemic challenge. Here, we extended this approach by studying leukocytes derived from lungs and livers of mice immunized by parenteral and respiratory routes with F. tularensis vaccines. Liver and lung leukocytes derived from intradermally and intranasally vaccinated mice controlled in vitro Francisella Live Vaccine Strain (LVS) intramacrophage replication in patterns similar to those of splenocytes. Gene expression analyses of potential correlates also revealed similar patterns in liver cells and splenocytes. In some cases (e. g., tumor necrosis factor alpha [TNF-alpha], interleukin 22 [IL-22], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), liver cells exhibited even higher relative gene expression, whereas fewer genes exhibited differential expression in lung cells. In contrast with their strong ability to control LVS replication, splenocytes from intranasally vaccinated mice expressed few genes with a hierarchy of expression similar to that of splenocytes from intradermally vaccinated mice. Thus, the relative levels of gene expression vary between cell types from different organs and by vaccination route. Most importantly, because studies comparing cell sources and routes of vaccination supported the predictive validity of this coculture and gene quantification approach, we combined in vitro LVS replication with gene expression data to develop analytical models that discriminated between vaccine groups and successfully predicted the degree of vaccine efficacy. Thus, this strategy remains a promising means of identifying and quantifying correlative T cell responses. IMPORTANCE Identifying and quantifying correlates of protection is especially challenging for intracellular bacteria, including Francisella tularensis. F. tularensis is classified as a category A bioterrorism agent, and no vaccines have been licensed in the United States, but tularemia is a rare disease. Therefore, clinical trials to test promising vaccines are impractical. In this report, we further evaluated a novel approach to developing correlates by assessing T cell immune responses in lungs and livers of differentially vaccinated mice; these nonprofessional immune tissues are colonized by Francisella. The relative degree of vaccine efficacy against systemic challenge was reflected by the ability of immune T cells, particularly liver T cells, to control the intramacrophage replication of bacteria in vitro and by relative gene expression of several immunological mediators. We therefore developed analytical models that combined bacterial replication data and gene expression data. Several resulting models provided excellent discrimination between vaccines of different efficacies. C1 [De Pascalis, Roberto; Chou, Alicia Y.; Kennett, Nikki J.; Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Ryden, Patrik] Umea Univ, Dept Math & Math Stat, Umea, Sweden. [Sjostedt, Anders] Umea Univ, Dept Clin Microbiol, Umea, Sweden. [Sjostedt, Anders] Umea Univ, Lab Mol Infect Med Sweden MIMS, Umea, Sweden. RP De Pascalis, R (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM roberto.depascalis@fda.hhs.gov RI Ryden, Patrik/I-4201-2016; OI Ryden, Patrik/0000-0002-0577-123X; Sjostedt, Anders/0000-0002-0768-8405 FU National Institute of Allergy and Infectious Diseases [Y1-AI-6153-01/224-06-1322]; U.S. Department of Energy; U.S. Food and Drug Administration; Swedish Medical Research Council [K2013-56X-22356] FX This work was supported in part by an interagency agreement with the National Institute of Allergy and Infectious Diseases (Y1-AI-6153-01/224-06-1322) and by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. Grant support was also obtained from the Swedish Medical Research Council (K2013-56X-22356). NR 43 TC 6 Z9 6 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAR-APR PY 2014 VL 5 IS 2 AR e00936-13 DI 10.1128/mBio.00936-13 PG 12 WC Microbiology SC Microbiology GA AH1XR UT WOS:000335915600014 PM 24713322 ER PT J AU Behrens, AM Casey, BJ Sikorski, MJ Wu, KL Tutak, W Sandler, AD Kofinas, P AF Behrens, Adam M. Casey, Brendan J. Sikorski, Michael J. Wu, Kyle L. Tutak, Wojtek Sandler, Anthony D. Kofinas, Peter TI In Situ Deposition of PLGA Nanofibers via Solution Blow Spinning SO ACS MACRO LETTERS LA English DT Article ID CARBON-DIOXIDE; FIBRIN FIBER; AIR; ANASTOMOSIS; SCAFFOLDS; MEMBRANE; DELIVERY; LEAKS; TRIAL AB Nanofiber mats and scaffolds have been widely investigated for biomedical applications. Commonly fabricated using electrospinning, nanofibers are generated ex situ using an apparatus that requires high voltages and an electrically conductive target. We report the use of solution blow spinning to generate conformal nanofiber mats/meshes on any surface in situ, utilizing only a commercial airbrush and compressed CO2. Solution and deposition conditions of PLGA nanofibers were optimized and mechanical properties characterized with dynamic mechanical analysis. Nanofiber mat degradation was monitored for morphologic and molecular weight changes in vitro. Biocompatibility of the direct deposition of nanofibers onto two cell lines was demonstrated in vitro and interaction with blood was qualitatively assessed with scanning electron microscopy. A pilot animal study illustrated the wide potential of this technique across multiple surgical applications, including its use as a surgical sealant, hemostatic, and buttress for tissue repair. C1 [Behrens, Adam M.; Sikorski, Michael J.; Kofinas, Peter] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Casey, Brendan J.] US FDA, Off Med Prod & Tobacco, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs,Div Chem & Mat Sci, Silver Spring, MD USA. [Wu, Kyle L.; Sandler, Anthony D.] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA. [Tutak, Wojtek] NIST, Amer Dent Assoc Fdn, Gaithersburg, MD 20899 USA. RP Kofinas, P (reprint author), Univ Maryland, Fischell Dept Bioengn, 2330 Jeong H Kim Engn Bldg, College Pk, MD 20742 USA. EM kofinas@umd.edu OI Kofinas, Peter/0000-0001-6657-3037 FU Warren Citrin Graduate Fellowship; Sheikh Zayed Institute for Surgical Innovation FX We would like to acknowledge the Warren Citrin Graduate Fellowship and the Sheikh Zayed Institute for Surgical Innovation for supporting this work. We would also like to thank Dr. Qijin Lu and Dr. Richard Malinauskas for their assistance with the in vitro blood protocols along with Dr. Eric Sussman for his help with the cell viability experiments. All research was performed through the University of Maryland and Children's National Medical Center. The conclusions made and items identified by brand name are the choice of the authors' and are not to be construed as conveying an official endorsement by the U.S. Food and Drug Administration. NR 33 TC 34 Z9 34 U1 10 U2 75 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2161-1653 J9 ACS MACRO LETT JI ACS Macro Lett. PD MAR PY 2014 VL 3 IS 3 BP 249 EP 254 DI 10.1021/mz500049x PG 6 WC Polymer Science SC Polymer Science GA AG9EB UT WOS:000335720400008 ER PT J AU Chelonis, JJ Cox, AR Karr, MJ Prunty, PK Baldwin, RL Paule, MG AF Chelonis, John J. Cox, Andrew R. Karr, Michael J. Prunty, Patricia K. Baldwin, Ronald L. Paule, Merle G. TI Comparison of delayed matching-to-sample performance in monkeys and children SO BEHAVIOURAL PROCESSES LA English DT Article DE Forgetting; Delayed matching-to-sample; Proactive interference; Attention; Monkeys; Children ID SHORT-TERM-MEMORY; DEFICIT HYPERACTIVITY DISORDER; VISUAL WORKING-MEMORY; OPERANT TEST BATTERY; PROACTIVE-INTERFERENCE; RHESUS-MONKEYS; STIMULANT MEDICATION; RECOGNITION MEMORY; NONHUMAN-PRIMATES; TASK-PERFORMANCE AB Although research has consistently demonstrated that accuracy on a variety of memory tasks decreases as delay increases, relatively little research has been conducted to quantify this relationship across development in humans or directly compare rates of forgetting between humans and monkeys. This study utilized a delayed matching-to-sample (DMTS) task to compare the relative contributions of proactive interference and attention on the rate of forgetting in monkeys and children. The performance of 1125 children from four to fourteen years of age and 10 adult rhesus monkeys was compared. For this DMTS task, a shape was displayed on the center one of three press-plates. After a delay, the subjects were required to match the original shape with one of three choice shapes to receive a banana-flavored food pellet for monkeys, or a nickel for children. A modified power function provided an excellent fit for the data for monkeys and children. The forgetting rates in children decreased with age, and the forgetting rates for monkeys were most comparable to those of younger children. The data also suggest that proactive interference did not significantly contribute to the forgetting rates for monkeys or younger children. Further, the monkeys appeared to attend to the task at a level similar to that of younger children as evidenced by the similarities in response latencies. The results from this study indicate that the rate of forgetting in monkeys, as well as the mechanisms underlying this rate, appears to share more similarities with that of younger children than of older children. Published by Elsevier B.V. C1 [Chelonis, John J.; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. [Chelonis, John J.; Cox, Andrew R.; Karr, Michael J.; Baldwin, Ronald L.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72205 USA. [Karr, Michael J.; Paule, Merle G.] Hendrix Coll, Dept Psychol, Conway, AR USA. [Prunty, Patricia K.] Lindenwood Univ Belleville, Dept Psychol, Belleville, IL USA. RP Chelonis, JJ (reprint author), Arkansas Childrens Hosp, Dept Pediat CARE, 1 Childrens Way,Slot 512-26, Little Rock, AR 72202 USA. EM john.chelonis@fda.hhs.gov NR 60 TC 3 Z9 3 U1 3 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0376-6357 EI 1872-8308 J9 BEHAV PROCESS JI Behav. Processes PD MAR PY 2014 VL 103 BP 261 EP 268 DI 10.1016/j.beproc.2014.01.002 PG 8 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA AG7US UT WOS:000335624900038 PM 24440984 ER PT J AU Frattarelli, DAC Galinkin, JL Green, TP Johnson, TD Neville, KA Paul, IM Van den Anker, JN Knight, M Alexander, JJ Kilpatrick, SJ Cragan, JD Rieder, MJ Robb, AS Sachs, H Zajicek, A Haro, T Koteras, RK Del Monte, M AF Frattarelli, Daniel A. C. Galinkin, Jeffrey L. Green, Thomas P. Johnson, Timothy D. Neville, Kathleen A. Paul, Ian M. Van den Anker, John N. Knight, Matthew Alexander, John J. Kilpatrick, Sarah J. Cragan, Janet D. Rieder, Michael J. Robb, Adelaide S. Sachs, Hari Zajicek, Anne Haro, Tamar Koteras, Raymond K. Del Monte, Mark CA COMM DRUGS TI Off-Label Use of Drugs in Children SO PEDIATRICS LA English DT Article DE off-label drug use; pharmaceuticals; pediatrics; infants; children; adolescents; prescribing AB The passage of the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act has collectively resulted in an improvement in rational prescribing for children, including more than 500 labeling changes. However, off-label drug use remains an important public health issue for infants, children, and adolescents, because an overwhelming number of drugs still have no information in the labeling for use in pediatrics. The purpose of off-label use is to benefit the individual patient. Practitioners use their professional judgment to determine these uses. As such, the term off-label does not imply an improper, illegal, contraindicated, or investigational use. Therapeutic decision-making must always rely on the best available evidence and the importance of the benefit for the individual patient. C1 [Alexander, John J.; Sachs, Hari] US FDA, Rockville, MD 20857 USA. [Kilpatrick, Sarah J.] Amer Coll Obstetricians & Gynecologists, Washington, DC USA. [Cragan, Janet D.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Rieder, Michael J.] Canadian Pediat Soc, Ottawa, ON, Canada. [Robb, Adelaide S.] Amer Acad Child & Adolescent Psychiat, Washington, DC USA. [Zajicek, Anne] NIH, Bethesda, MD USA. OI Paul, Ian/0000-0002-6344-8609 NR 7 TC 48 Z9 52 U1 0 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAR PY 2014 VL 133 IS 3 BP 563 EP 567 DI 10.1542/peds.2013-4060 PG 5 WC Pediatrics SC Pediatrics GA AG3PB UT WOS:000335330700036 PM 24567009 ER PT J AU Murphy, D Reaman, G Jensen, CV AF Murphy, Dianne Reaman, Gregory Jensen, Capt Valerie TI Pediatric Oncology Drug Shortages: A Multifaceted Problem SO PEDIATRICS LA English DT Editorial Material DE oncology drug shortages C1 [Murphy, Dianne] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. [Reaman, Gregory] US FDA, Off Hematol & Oncol Prod, Silver Spring, MD 20993 USA. [Jensen, Capt Valerie] Ctr Drugs Food & Drug Adm, Silver Spring, MD USA. RP Murphy, D (reprint author), US FDA, Off Pediat Therapeut, Off Commissioner, 10903 New Hampshire Ave,W032-5150, Silver Spring, MD 20993 USA. EM dianne.murphy@fda.hhs.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAR PY 2014 VL 133 IS 3 BP E728 EP E729 DI 10.1542/peds.2013-4018 PG 2 WC Pediatrics SC Pediatrics GA AG3PB UT WOS:000335330700056 PM 24488740 ER PT J AU Isbrucker, R Arciniega, J McFarland, R Chapsal, JM Xing, D Bache, C Nelson, S Costanzo, A Hoonakker, M Castiaux, A Halder, M Casey, W Johnson, N Jones, B Doelling, V Sprankle, C Rinckel, L Stokes, W AF Isbrucker, Richard Arciniega, Juan McFarland, Richard Chapsal, Jean-Michel Xing, Dorothy Bache, Christina Nelson, Sue Costanzo, Angele Hoonakker, Marieke Castiaux, Amelie Halder, Marlies Casey, Warren Johnson, Nelson Jones, Brett Doelling, Vivian Sprankle, Cathy Rinckel, Lori Stokes, William TI Report on the international workshop on alternatives to the murine histamine sensitization test (HIST) for acellular pertussis vaccines: State of the science and the path forward SO BIOLOGICALS LA English DT Article DE Pertussis toxin; Acellular pertussis vaccines; Alternative methods; Safety; Biochemical assays; Cell-based assays ID TOXIN; ASSAY; STRATEGIES AB Regulatory authorities require safety and potency testing prior to the release of each production lot of acellular pertussis (aP)-containing vaccines. Currently, the murine histamine sensitization test (HIST) is used to evaluate the presence of residual pertussis toxin in aP containing vaccines. However, the testing requires the use of a significant number of mice and results in unrelieved pain and distress. NICEATM, ICCVAM, their partners in the International Cooperation on Alternative Test Methods, and the International Working Group for Alternatives to HIST organized a workshop to discuss recent developments in alternative assays to the HIST, review data from an international collaborative study on non-animal alternative tests that might replace the HIST, and address the path toward global acceptance of this type of method. Currently, there are three potential alternative methods to HIST. Participants agreed that no single in vitro method was sufficiently developed for harmonized validation studies at this time. It is unlikely that any single in vitro method would be applicable to all aP vaccines without modification, due to differences between vaccines. Workshop participants recommended further optimization of cell-based assays under development. Participants agreed that the next international collaborative studies should commence in 2013 based on discussions during this workshop. C1 [Isbrucker, Richard] Hlth Canada, Biol & Genet Therapies Directorate, Ottawa, ON K1A 0K9, Canada. [Arciniega, Juan; McFarland, Richard] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Chapsal, Jean-Michel] Sanofi Pasteur, Lyon, France. [Xing, Dorothy] Natl Inst Biol Stand & Controls, Div Bacteriol, S Mimms EN6 3QG, Herts, England. [Bache, Christina] Paul Ehrlich Inst, D-63225 Langen, Germany. [Nelson, Sue] Sanofi Pasteur, Toronto, ON, Canada. [Costanzo, Angele] European Directorate Qual Med & Healthcare, Strasbourg, France. [Hoonakker, Marieke] Netherlands Vaccine Inst, NL-3721 MA Bilthoven, Netherlands. [Castiaux, Amelie] GlaxoSmithKline, B-1330 Rixensart, Belgium. [Halder, Marlies] Inst Hlth & Consumer Protect, European Commiss Joint Res Ctr, European Union Reference Lab Alternat Anim Testin, I-21027 Ispra, Varese, Italy. [Casey, Warren; Stokes, William] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Ctr Evaluat, Alternat Toxicol Methods Div,NIH, Res Triangle Pk, NC 27709 USA. [Johnson, Nelson; Jones, Brett; Doelling, Vivian; Sprankle, Cathy; Rinckel, Lori; Stokes, William] Integrated Lab Syst Inc, Morrisville, NC 27560 USA. RP Isbrucker, R (reprint author), Hlth Canada, Biol & Genet Therapies Directorate, 100 Eglantine Dr, Ottawa, ON K1A 0K9, Canada. EM richard.isbrucker@hc-sc.gc.ca FU NICEATM; ICCVAM; EURL ECVAM; JaCVAM; International Cooperation on Alternative Test Methods FX The authors extend their sincere appreciation to all participants in the international workshop for their contributions leading to the workshop conclusions and recommendations. The members of the HIST Workshop Organizing Committee, the International Working Group for Alternatives to HIST, ICCVAM Interagency Biologics Working Group, and NICEATM staff are acknowledged for their contributions to the planning of the workshop. All of the invited experts are acknowledged for their contributions to roundtable discussions and workshop proceedings. Participating national and international validation organizations from the International Cooperation on Alternative Test Methods, including NICEATM, ICCVAM, EURL ECVAM, and JaCVAM, are gratefully acknowledged for their scientific contributions and financial support. Finally, the authors gratefully acknowledge Dr. Raymond Tice and Dr. John Bucher from the National Institute of Environmental Health Sciences, National Institutes of Health, USA, for their review of the manuscript. NR 20 TC 0 Z9 0 U1 2 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 EI 1095-8320 J9 BIOLOGICALS JI Biologicals PD MAR PY 2014 VL 42 IS 2 BP 114 EP 122 DI 10.1016/j.biologicals.2013.11.011 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA AG1UR UT WOS:000335202200008 PM 24394373 ER PT J AU Panos, JJ Law, CD Ferguson, SA AF Panos, John J. Law, C. Delbert Ferguson, Sherry A. TI Effects of perinatal methylphenidate (MPH) treatment in male and female Sprague-Dawley offspring SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Methylphenidate; Ritalinic acid; Hormone; Behavior; Pregnancy; Rat ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CONDITIONED PLACE PREFERENCE; ADULT RATS; DEVELOPMENTAL TOXICITY; ORAL METHYLPHENIDATE; PRENATAL EXPOSURE; SERUM-LEVELS; DOUBLE-BLIND; D,L-METHYLPHENIDATE; BEHAVIORS AB MPH is a common treatment for adult Attention Deficit Hyperactivity Disorder (ADHD). However, little information exists regarding its safety during pregnancy and thus, women with ADHD face difficult decisions regarding continued use during pregnancy. Here, Sprague-Dawley rats were orally treated 3x/day with 0 (control), 6 (low), 18 (mid), or 42 (high) mg MPH/kg/day (i.e., 0, 2, 6, or 14 mg/kg at each treatment time) on gestational days 6-21. On postnatal days (PNDs) 1-21, all offspring/litter were orally treated 2 x/day with the same dose. Righting reflex (PNDs 3-6) and slant board performance (PNDs 8-11) were assessed. T3, T4, E-2, testosterone, LH and corticosterone were measured at PND 22. Separate pregnant dams and resulting litters were used for serum MPH measurements. MPH treatment had mild, but significant, effects on gestational body weight and food intake. Birth weight of high MPH offspring was 5% more than controls (p < 0.0500). Relative to same-sex controls on PNDs 1-22, low and mid MPH males weighed more (p < 0.0094), low MPH females weighed more (p < 0.0001), while high MPH females weighed less (p < 0.0397). PND 22 serum E2 levels were significantly decreased (20-25%) in high MPH males and females (p < 0.0500). Behavioral performance was unaffected by treatment. Serum MPH levels of the low MPH pregnant dams were within the range produced by therapeutic MPH doses in adults; however, offspring levels in all groups were substantially higher. These results indicate that developmental MPH treatment has mild effects on gestational body weight and food intake and offspring preweaning body weight. Potential functional consequences of decreased serum E2 levels are not clear, but may impact later behavior or physiology. Published by Elsevier Inc. C1 [Panos, John J.; Law, C. Delbert; Ferguson, Sherry A.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov OI Panos, John/0000-0002-7607-7114 FU National Center for Toxicological Research/Food and Drug Administration [E7318] FX This work was supported by the National Center for Toxicological Research/Food and Drug Administration [Protocol # E7318 to S.A.F.]. The authors are grateful for the technical expertise provided by the animal care staff of the Priority One Corporation. We especially are indebted to expert statistician Mr. Robert Paul Felton of the Division of Bioinformatics and Biostatistics for his careful analyses and for the assistance of Ms. Kaitlyn Maier and Mr. Wesley Perry. NR 49 TC 6 Z9 7 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 2014 VL 42 BP 9 EP 16 DI 10.1016/j.ntt.2014.01.004 PG 8 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA AG0HH UT WOS:000335096000002 PM 24444667 ER PT J AU Hungerford, JM Gago-Martinez, A AF Hungerford, James M. Gago-Martinez, Ana TI Marine Toxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Editorial Material C1 [Hungerford, James M.] US FDA, Appl Technol Ctr, Pacific Northwest Lab, Bothell, WA 98021 USA. [Gago-Martinez, Ana] Univ Vigo, Dept Quim Analit & Alimentaria, Vigo 36310, Spain. RP Hungerford, JM (reprint author), US FDA, Appl Technol Ctr, Pacific Northwest Lab, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2014 VL 97 IS 2 BP 283 EP 284 DI 10.5740/jaoacint.SGEHungerford_Intro PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA AF2UP UT WOS:000334568300001 PM 24830137 ER PT J AU Manger, R Woodle, D Berger, A Dickey, RW Jester, E Yasumoto, T Lewis, R Hawryluk, T Hungerford, J AF Manger, Ronald Woodle, Doug Berger, Andrew Dickey, Robert W. Jester, Edward Yasumoto, Takeshi Lewis, Richard Hawryluk, Timothy Hungerford, James TI Flow Cytometric-Membrane Potential Detection of Sodium Channel Active Marine Toxins: Application to Ciguatoxins in Fish Muscle and Feasibility of Automating Saxitoxin Detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FLUOROMETRIC MICROPLATE ASSAY; PARALYTIC SHELLFISH POISON; TISSUE-CULTURE BIOASSAY; CARIBBEAN CIGUATOXINS; CELL BIOASSAY; BREVETOXINS; CIGUATERA; TETRODOTOXIN; ANTILLATOXIN; ACTIVATORS AB Ciguatoxins are potent neurotoxins with a significant public health impact. Cytotoxicity assays have allowed the most sensitive means of detection of ciguatoxin-like activity without reliance on mouse bioassays and have been invaluable in studying outbreaks. An improvement of these cell-based assays is presented here in which rapid flow cytometric detection of ciguatoxins and saxitoxins is demonstrated using fluorescent voltage sensitive dyes. A depolarization response can be detected directly due to ciguatoxin alone; however, an approximate 1000-fold increase in sensitivity is observed in the presence of veratridine. These results demonstrate that flow cytometric assessment of ciguatoxins is possible at levels approaching the trace detection limits of our earlier cytotoxicity assays, however, with a significant reduction in analysis time. Preliminary results are also presented for detection of brevetoxins and for automation and throughput improvements to a previously described method for detecting saxitoxins in shellfish extracts. C1 [Manger, Ronald; Woodle, Doug; Berger, Andrew] Fred Hutchinson Canc Res Ctr, Biol Prod Facil, Seattle, WA 98109 USA. [Dickey, Robert W.; Jester, Edward] US FDA, Gulf Coast Seafood Lab, Ctr Food Safety & Appl Nutr, Dauphin Isl, AL USA. [Yasumoto, Takeshi] Japan Food Res Labs JFRL, Tokyo, Japan. [Lewis, Richard] Univ Queensland, Brisbane, Qld, Australia. [Hawryluk, Timothy] US FDA, Northeast Reg Lab, Jamaica, NY USA. [Hungerford, James] US FDA, Appl Technol Ctr, Bothell, WA USA. RP Manger, R (reprint author), Fred Hutchinson Canc Res Ctr, Biol Prod Facil, Seattle, WA 98109 USA. EM rmanger@fhcrc.org OI Lewis, Richard/0000-0003-3470-923X NR 51 TC 5 Z9 6 U1 2 U2 26 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2014 VL 97 IS 2 BP 299 EP 306 DI 10.5740/jaoacint.SGEManger PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA AF2UP UT WOS:000334568300004 PM 24830140 ER PT J AU Nyman, PJ Limm, W Begley, TH Chirtel, SJ AF Nyman, Patricia J. Limm, William Begley, Timothy H. Chirtel, Stuart J. TI Single-Laboratory Validation of a Method for the Determination of Select Volatile Organic Compounds in Foods by Using Vacuum Distillation with Gas Chromatography/Mass Spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID STANDARD ADDITIONS; MASS-SPECTROMETRY; STYRENE MIGRATION; MODEL SYSTEMS; HEADSPACE; BENZENE; FURAN; POLYSTYRENE; PURPOSE; DRINKS AB Recent studies showed that headspace and purge and trap methods have limitations when used to determine volatile organic compounds (VOCs) in foods, including matrix effects and artifact formation from precursors present in the sample matrix or from thermal decomposition. U.S. Environmental Protection Agency Method 8261A liberates VOCs from the sample matrix by using vacuum distillation at room temperature. The method was modified and validated for the determination of furan, chloroform, benzene, trichloroethene, toluene, and sytrene in infant formula, canned tuna (in water), peanut butter, and an orange beverage (orange-flavored noncarbonated beverage). The validation studies showed that the LOQ values ranged from 0.05 ng/g toluene in infant formula to 5.10 ng/g toluene in peanut butter. Fortified recoveries were determined at the first, second, and third standard additions, and concentrations ranged from 0.07 to 6.9 ng/g. When quantified by the method of standard additions, the recoveries ranged from 56 to 218% at the first standard addition and 89 to 117% at the third. The validated method was used to conduct a survey of the targeted VOCs in 18 foods. The amounts found ranged from none detected to 73.8 ng/g furan in sweet potato baby food. C1 [Nyman, Patricia J.; Limm, William; Begley, Timothy H.; Chirtel, Stuart J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Nyman, PJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 706,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Patricia.Nyman@fda.hhs.gov NR 27 TC 3 Z9 3 U1 1 U2 18 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2014 VL 97 IS 2 BP 510 EP 520 DI 10.5740/jaoacint.13-294 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA AF2UP UT WOS:000334568300028 PM 24830164 ER PT J AU McClure, FD Lee, JK AF McClure, Foster D. Lee, Jung K. TI Use of Prediction Methods to Assess Laboratory Bias and Mean Values Associated with an Inter laboratory Study for Method Validation and/or Proficiency Testing SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Two methods of prediction of random variables, best predictor (BP) and best linear unbiased predictor (BLUP), are discussed as potential statistical methods to predict laboratory true mean and bias values using the sample laboratory mean ((y) over bar (i)) from interlaboratory studies. The predictions developed here require that the interlaboratory and/or proficiency study be designed and conducted in a manner consistent with the assumptions of a one-way completely randomized model (CRM). Under the CRM the individual laboratory true mean and bias are not parameters but are defined to be random variables that are unobservable and considered as realized values that cannot be estimated but can be predicted using methods of "prediction." The BP method is applicable when all salient parameters are known, e.g., the consensus true overall mean (p) and repeatability and reproducibility components (sigma(2)(r) and sigma(2)(R)), while the BLUP method is useful when sigma(2)(r) and sigma(2)(R) are known, but mu is estimated by the generalized least square estimator. Although the derivations of predictors are obtained by minimizing the mean-square error under the CRM assumptions, the predictors are the expected laboratory true mean and bias given the sample laboratory mean, i.e., conditional expectation. C1 [McClure, Foster D.; Lee, Jung K.] US FDA, Ctr Food Safety & Appl Nutr, Off Analyt & Outreach, Div Publ Hlth Informat & Analyt, College Pk, MD 20740 USA. RP McClure, FD (reprint author), POB 413, Frederick, MD 21705 USA. EM fdmc5100@yahoo.com NR 11 TC 0 Z9 0 U1 0 U2 1 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2014 VL 97 IS 2 BP 624 EP 629 DI 10.5740/jaoacint.12-457 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA AF2UP UT WOS:000334568300040 PM 24830176 ER PT J AU Borges, S Chen, YF Laughren, TP Temple, R Patel, HD David, PA Mathis, M Unger, E Yang, PL Khin, NA AF Borges, Silvana Chen, Yeh-Fong Laughren, Thomas P. Temple, Robert Patel, Hiren D. David, Paul A. Mathis, Mitchell Unger, Ellis Yang, Peiling Khin, Ni A. TI Review of Maintenance Trials for Major Depressive Disorder: A 25-Year Perspective From the US Food and Drug Administration SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID RELAPSE PREVENTION; RESIDUAL SYMPTOMS; METAANALYSIS; ANTIDEPRESSANTS; RECURRENCE; REMISSION; RECOVERY AB Objective: The maintenance efficacy of antidepressants is usually assessed in postmarketing studies with a randomized withdrawal design. This report explores differences in relapse rates, trial characteristics, and success rates in maintenance efficacy studies submitted to the US Food and Drug Administration (FDA) over a 25-year period. Data Sources: Clinical data from all maintenance trials with antidepressants submitted to FDA between 1987 and 2012. Study Selection: Efficacy data were compiled from 15 maintenance clinical trials in adults diagnosed with major depressive disorder according to DSM-III or DSM-IV criteria. Data Extraction: Trial characteristics, relapse rates, and time to relapse in each study were examined. Results: Relapse rates were significantly lower (P <.05) in the drug arm than in the placebo arm in every study, with a mean relapse rate difference of 18% and an average percent reduction in relapse rate of 52% compared to placebo. Only 6% of the relapse events occurred in the first 2 weeks of the doubleblind phase. The separation between treatment arms continued to increase throughout the double-blind phase only in the trial with longest response stabilization period. Conclusions: Antidepressant maintenance trials have a high rate of success, indicating a benefit of continuing drug treatment after initial response to an antidepressant. This benefit appears to result mainly from a decreased rate of recurrent depression rather than from an effect of drug withdrawal in the placebo groups. C1 [Borges, Silvana; Patel, Hiren D.; David, Paul A.; Mathis, Mitchell] Food & Drug Adm 1, Div Psychiat Prod, Off New Drugs, Silver Spring, MD 20993 USA. [Temple, Robert] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Laughren, Thomas P.] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA USA. [Laughren, Thomas P.] NIMH, Bethesda, MD 20892 USA. RP Borges, S (reprint author), Food & Drug Adm, Div Psychiat Prod, 10903 New Hampshire Ave,Bldg 22,Rm 4159, Silver Spring, MD 20993 USA. EM silvana.borges@fda.hhs.gov NR 24 TC 17 Z9 17 U1 4 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2014 VL 75 IS 3 BP 205 EP 214 DI 10.4088/JCP.13r08722 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AF0RP UT WOS:000334422000005 PM 24717376 ER PT J AU Vitcheva, V Kondeva-Burdina, M Simeonova, R Mitcheva, M AF Vitcheva, Vessela Kondeva-Burdina, Magdalena Simeonova, Rumyana Mitcheva, Mitka TI COCAINE TOXICITY IN FRESHLY ISOLATED RAT HEPATOCYTES - ROLE OF CYP 2B AND CYP 3A SO FARMACIA LA English DT Article DE cocaine; hepatocytes; CYP 3A; CYP 2B ID METABOLISM; HEPATOTOXICITY; LIVER; FETAL AB Cocaine is a psychoactive compound that undergoes extensive hepatic biotransformation leading to formation of toxic metabolites responsible for its hepatotoxicity. The objectives of this study were to investigate the influence of induction and inhibition on cocaine hepatotoxicity examined in freshly isolated rat hepatocytes. For investigating the role of induction male Wistar rats have been treated in vivo with phenobarbital (75mg.kg-(1), 4 days) and then isolated hepatocytes were exposed to cocaine (50 mu mol.L-1 for one hour). Compared to control non-treated hepatocytes phenobarbital induction resulted in greater cocaine hepatotoxicity, witnessed by decrease in cell viability by 52%, increase in lactate dehydrogenase (LDH) leakage into the medium by 120%, depletion of reduced gluthathione (GSH) levels by 84% and increase in malondialdehyde (MDA) quantity by 74%. Experimental data in the literature reported two major cytochrome P 450 isoforms CYP 3A and CYP 2B to be involved in cocaine biotransformation and toxicity. In order to trace the relative contribution of these isoforms to cocaine hepatotoxicity in rats, isolated hepatocytes were pre-incubated for 15 min with amiodarone (15 mu mol(.)L(-1)) and with chloramphenicol (100 mu mol.L-1) inhibitors of CYP 3A and CYP 2B, respectively. Pre-incubation with either of the inhibitors ameliorated cocaine hepatotoxicity. Our results prove the role of both isoforms CYP 3A and CYP 2B in cocaine biotransformation in rats. C1 [Vitcheva, Vessela; Kondeva-Burdina, Magdalena; Simeonova, Rumyana; Mitcheva, Mitka] Med Univ Sofia, Fac Pharm, Dept Pharmacol Pharmacotherapy & Toxicol, Lab Drug Metab & Tox, Sofia 1000, Bulgaria. [Vitcheva, Vessela] US FDA, Ctr Food Safety & Nutr CFSAN, College Pk, MD USA. RP Vitcheva, V (reprint author), Med Univ Sofia, Fac Pharm, Dept Pharmacol Pharmacotherapy & Toxicol, Lab Drug Metab & Tox, 2 Dunav Str, Sofia 1000, Bulgaria. EM vesselavitcheva@yahoo.com NR 17 TC 0 Z9 0 U1 0 U2 1 PU SOC STINTE FARMACEUTICE ROMANIA PI BUCURESTI PA BUCURESTI, STR TRAIAN VUIA 6, SECT 1, BUCURESTI, 020956, ROMANIA SN 0014-8237 EI 2065-0019 J9 FARMACIA JI Farmacia PD MAR-APR PY 2014 VL 62 IS 2 BP 264 EP 272 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF0GG UT WOS:000334391500004 ER PT J AU Fox, ER Sweet, BV Jensen, V AF Fox, Erin R. Sweet, Burgunda V. Jensen, Valerie TI Drug Shortages: A Complex Health Care Crisis SO MAYO CLINIC PROCEEDINGS LA English DT Article ID UNITED-STATES; ANESTHESIA PRACTICE; PATIENT SAFETY; SHORT-TERM; LONG-TERM; IMPACT; CANCER; HOSPITALS; PREMATURE; ONCOLOGY AB National tracking of drug shortages began in 2001. However, a significant increase in the number of shortages began in late 2009, with numbers reaching what many have termed crisis level. The typical drug in short supply is a generic product administered by injection. Common classes of drugs affected by shortages include anesthesia medications, antibiotics, pain medications, nutrition and electrolyte products, and chemotherapy agents. The economic and clinical effects of drug shortages are significant. The financial effect of drug shortages is estimated to be hundreds of millions of dollars annually for health systems across the United States. Clinically, patients have been harmed by the lack of drugs or inferior alternatives, resulting in more than 15 documented deaths. Drug shortages occur for a variety of reasons. Generic injectable drugs are particularly susceptible to drug shortages because there are few manufacturers of these products and all manufacturers are running at full capacity. In addition, some manufacturers have had production problems, resulting in poor quality product. Although many suppliers are working to upgrade facilities and add additional manufacturing lines, these activities take time. A number of stakeholder organizations have been involved in meetings to further determine the causes and effects of drug shortages. A new law was enacted in July 2012 that granted the Food and Drug Administration additional tools to address the drug shortage crisis. The future of drug shortages is unknown, but there are hopeful indications that quality improvements and additional capacity may decrease the number of drug shortages in the years to come. (C) 2014 Mayo Foundation for Medical Education and Research C1 [Fox, Erin R.] Univ Utah, Hosp & Clin, Salt Lake City, UT USA. [Sweet, Burgunda V.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Jensen, Valerie] Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD USA. RP Fox, ER (reprint author), 50 N Med Dr,Room A-050, Salt Lake City, UT 84132 USA. EM Erin.Fox@hsc.utah.edu NR 55 TC 25 Z9 27 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAR PY 2014 VL 89 IS 3 BP 361 EP 373 DI 10.1016/j.mayocp.2013.11.014 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA AC3DY UT WOS:000332396400015 PM 24582195 ER PT J AU Zhang, YH Mann, D Raymick, J Sarkar, S Paule, MG Lahiri, DK Dumas, M Bell-Cohen, A Schmued, LC AF Zhang, Yi-Hong Mann, Dushyant Raymick, James Sarkar, Sumit Paule, Merle G. Lahiri, Debomoy K. Dumas, Melanie Bell-Cohen, Ashlee Schmued, Larry C. TI K114 Inhibits A-beta Aggregation and Inflammation In Vitro and In Vivo in AD/Tg Mice SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; amyloid-beta aggregation; amyloid plaques; astrocytes; K114 ID AMYLOID PRECURSOR PROTEIN; LOW-DENSITY-LIPOPROTEIN; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; CONGO RED; FIBRIL FORMATION; HUMAN CD68; ASTROCYTES; MICROGLIA; PATHOLOGY AB Alzheimer's disease (AD) is the most common age related human neurodegenerative disorder. The major histopathological characteristics of the AD brain are extracellular amyloid-beta (A beta) peptide loaded plaques and intraneuronal neurofibrillary tangles made of phosphorylated tau proteins. Amyloid plaques consist primarily of aggregated A beta(1-42) and A beta(1-40) peptides. The aim of our current study was to test novel ligands/agents with the potential to disrupt or inhibit the aggregation of A beta peptide, specifically K114, (trans, trans)-1-bromo-2,5-bis(4-hydroxystyryl) benzene, which was initially developed as a potential positron emission tomography (PET) ligand for the in vivo detection of amyloid plaques. Systemic administration of K114 has been shown in the AD/transgenic (Tg) mouse model to be capable of crossing the blood-brain barrier (BBB) and be colocalized with amyloid plaques. In this study we determined whether K114 has the potential to inhibit A beta aggregation in vitro in AD/Tg mice and also tested, in vivo, whether chronic daily orally administered K114 has any therapeutic potential as evidenced by inhibition or reduction of the deposits of amyloid aggregates in the brains of AD/Tg mice. Our results demonstrated that K114 strongly blocked, in vitro, the aggregation of A beta peptide in the amyloid plaques of AD/Tg mouse brain. Systemic treatment with K114 was also effective in significantly reducing the deposits of amyloid plaques in the brains of living transgenic AD mice. Additionally, K114 significantly inhibited the typically observed plaque associated astrocytic activation, as revealed by GFAP immunohistochemistry, suggesting possible anti-inflammatory properties. C1 [Zhang, Yi-Hong; Sarkar, Sumit; Paule, Merle G.; Schmued, Larry C.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mann, Dushyant] Wayne State Univ, Sch Med, Detroit, MI 48201 USA. [Raymick, James] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Lahiri, Debomoy K.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Lahiri, Debomoy K.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Dumas, Melanie] Prior One, Jefferson, AR 72079 USA. [Bell-Cohen, Ashlee] Univ Arkansas, Dept Chem, Fayetteville, AR 72701 USA. RP Schmued, LC (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM larry.schmued@fda.hhs.gov FU FDA/NCTR [E7273]; U.S. Department of Energy; FDA FX The contents of this manuscript do not necessarily reflect the views and policies of the U. S. Food and Drug Administration (FDA), nor does the mention of trade names or commercial products constitute endorsement or a recommendation for use. This work was supported by FDA/NCTR protocol E7273, and in part by an appointment (YZ) to the Research Participation Program at NCTR administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and FDA. NR 55 TC 5 Z9 5 U1 1 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD MAR PY 2014 VL 11 IS 3 BP 299 EP 308 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AE5VT UT WOS:000334058100011 PM 24552157 ER PT J AU Zubkova, I Duan, HY Wells, F Mostowski, H Chang, E Pirollo, K Krawczynski, K Lanford, R Major, M AF Zubkova, Iryna Duan, Hongying Wells, Frances Mostowski, Howard Chang, Esther Pirollo, Kathleen Krawczynski, Kris Lanford, Robert Major, Marian TI Hepatitis C Virus Clearance Correlates With HLA-DR Expression on Proliferating CD8+T Cells in Immune-Primed Chimpanzees SO HEPATOLOGY LA English DT Article ID CD8(+) T-CELLS; RECOVERED CHIMPANZEES; HCV INFECTION; YELLOW-FEVER; RESPONSES; PERSISTENCE; VACCINES; DETERMINANTS; IMMUNIZATION; REPLICATION AB Vaccination of chimpanzees against hepatitis C virus (HCV) using T-cell-based vaccines targeting nonstructural proteins has not resulted in the same levels of control and clearance as those seen in animals reexposed after HCV clearance. We hypothesized that the outcome of infection depends on the different subtypes of activated T cells. We used multicolor flow cytometry to evaluate activation (CD38+/HLA-DR+) and proliferation (Ki67+/Bcl-2-low) profiles of CD4+ and CD8+ T cells in peripheral blood before and after challenge in chimpanzees vaccinated using DNA/adenovirus, mock-vaccinated, and chimpanzees that had spontaneously cleared infection (rechallenged). The frequencies of activated or proliferating CD8+ T cells peaked at 2 weeks postchallenge in the vaccinated and rechallenged animals, coinciding with reductions in viral titers. However, the magnitude of the responses did not correlate with outcome or sustained control of viral replication. In contrast, proliferation of the CD8+ T cells coexpressing HLA-DR either with or without CD38 expression was significantly higher at challenge in animals that rapidly cleared HCV and remained so throughout the follow-up period. Conclusion: Our data suggest that the appearance of proliferating HLA-DR+/CD8+ T cells can be used as a predictor of a successfully primed memory immune response against HCV and as a marker of effective vaccination in clinical trials. (Hepatology 2014;59:803-813) C1 [Zubkova, Iryna; Duan, Hongying; Wells, Frances; Major, Marian] US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Mostowski, Howard] US FDA, Off Cellular & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Chang, Esther; Pirollo, Kathleen] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Krawczynski, Kris] Ctr Dis Control & Prevent, Div Viral Hepatitis, NCHHSTP, Atlanta, GA USA. [Lanford, Robert] SW Fdn Biomed Res, San Antonio, TX 78284 USA. RP Major, M (reprint author), Div Viral Prod, Lab Hepatitis Viruses, Bldg 29A Rm 1D10-HFM 448,8800 Rockville Pike, Bethesda, MD 20892 USA. EM marian.major@fda.hhs.gov FU CDC; FDA; U.S. Department of Energy; U.S. Food and Drug Administration FX Supported by CDC and FDA intramural research funds. The project was supported in part by the appointment of Hongying Duan to the Research Participation Program at CBER administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 34 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAR PY 2014 VL 59 IS 3 BP 803 EP 813 DI 10.1002/hep.26747 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AB4VH UT WOS:000331787500013 PM 24123114 ER PT J AU Fine, AJ Sorbello, A Kortepeter, C AF Fine, Andrew J. Sorbello, Alfred Kortepeter, Cindy TI Progressive Multifocal Leukoencephalopathy after Natalizumab Discontinuation: Few and True? Reply SO ANNALS OF NEUROLOGY LA English DT Letter C1 [Fine, Andrew J.; Sorbello, Alfred; Kortepeter, Cindy] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Fine, AJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2014 VL 75 IS 3 BP 462 EP 463 DI 10.1002/ana.24108 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AD8WS UT WOS:000333547000025 PM 24443375 ER PT J AU Fu, PP AF Fu, Peter P. TI Introduction to the Special Issue: Nanomaterials-Toxicology and medical applications SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Editorial Material C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Peter.Fu@fda.hhs.gov NR 0 TC 3 Z9 4 U1 0 U2 4 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 2014 VL 22 IS 1 SI SI BP 1 EP 2 DI 10.1016/j.jfda.2014.01.013 PG 2 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AE3CH UT WOS:000333854100001 PM 24673899 ER PT J AU Fan, Z Fu, PP Yu, HT Ray, PC AF Fan, Zhen Fu, Peter P. Yu, Hongtao Ray, Paresh C. TI Theranostic nanomedicine for cancer detection and treatment SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE Circulating tumor cell diagnosis; Combined therapy; Photothermal therapy; Selective cancer treatment; Theranostic nanomedicine ID CIRCULATING TUMOR-CELLS; IRON-OXIDE NANOPARTICLES; GOLD NANOPARTICLES; PHOTOTHERMAL THERAPY; METHYLENE-BLUE; DRUG-DELIVERY; PHOTODYNAMIC THERAPY; CONTROLLED-RELEASE; TARGETED THERAPY; PROSTATE-CANCER AB Cancer is the second leading cause of death in the USA according to the American Cancer Society. In the past 5 years, "theranostic nanomedicine", for both therapeutics and imaging, has shown to be "the right drug for the right patient at the right moment" to manage deadly cancers. This review article presents an overview of recent developments, mainly from the authors' laboratories, along with potential medical applications for theranostic nanomedicine including basic concepts and critical properties. Finally, we outline the future research direction and possible challenges for theranostic nanomedicine research. Copyright (C) 2014, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Fan, Zhen; Yu, Hongtao; Ray, Paresh C.] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. [Fu, Peter P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Ray, PC (reprint author), Jackson State Univ, Dept Chem & Biochem, 1400 JR Lynch St, Jackson, MS 39217 USA. EM paresh.c.ray@jsums.edu RI fan, zhen/N-5244-2014; fan, zhen/M-8774-2014 OI fan, zhen/0000-0001-7937-8441; fan, zhen/0000-0001-7937-8441 FU NSF-PREM [DMR-1205194] FX We thank Dr Jiekun Xuan for critical review of this manuscript. We are grateful for NSF-PREM funding (No. DMR-1205194) for nanomaterial and bioimaging. NR 76 TC 27 Z9 28 U1 14 U2 95 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 2014 VL 22 IS 1 SI SI BP 3 EP 17 DI 10.1016/j.jfda.2014.01.001 PG 15 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AE3CH UT WOS:000333854100002 PM 24673900 ER PT J AU He, WW Liu, YT Wamer, WG Yin, JJ AF He, Weiwei Liu, Yitong Wamer, Wayne G. Yin, Jun-Jie TI Electron spin resonance spectroscopy for the study of nanomaterial-mediated generation of reactive oxygen species SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE Electron spin resonance; Lipid peroxidation; Nanomaterials; Reactive oxygen species ID ZERO-VALENT IRON; HACAT KERATINOCYTES-GENERATION; RADICAL SCAVENGING CAPACITY; SURFACE-PLASMON RESONANCE; SIZE-DEPENDENT GENERATION; SILVER NANOPARTICLES; SINGLET OXYGEN; LIPID-PEROXIDATION; OXIDATIVE STRESS; OXIDE NANOPARTICLES AB Many of the biological applications and effects of nanomaterials are attributed to their ability to facilitate the generation of reactive oxygen species (ROS). Electron spin resonance (ESR) spectroscopy is a direct and reliable method to identify and quantify free radicals in both chemical and biological environments. In this review, we discuss the use of ESR spectroscopy to study ROS generation mediated by nanomaterials, which have various applications in biological, chemical, and materials science. In addition to introducing the theory of ESR, we present some modifications of the method such as spin trapping and spin labeling, which ultimately aid in the detection of short-lived free radicals. The capability of metal nanoparticles in mediating ROS generation and the related mechanisms are also presented. Copyright (C) 2014, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [He, Weiwei] Xuchang Univ, Inst Surface Micro & Nano Mat, Key Lab Micro Nano Mat Energy Storage & Convers H, Xuchang, Henan, Peoples R China. [He, Weiwei; Liu, Yitong; Wamer, Wayne G.; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM junjie.yin@fda.hhs.gov RI Liu, Yitong/H-2213-2011; Yin, Jun Jie /E-5619-2014 OI Liu, Yitong/0000-0002-4300-4349; FU US Food and Drug Administration (FDA) Nanotechnology CORES Program; Office of Cosmetics and Colors (CFSAN/FDA); National Natural Science Foundation of China [21303153] FX This work was supported by a regulatory science grant under the US Food and Drug Administration (FDA) Nanotechnology CORES Program and by the Office of Cosmetics and Colors (CFSAN/FDA), and was supported in part by an appointment (W.H.) to the Research Program at the CFSAN administered by the ORISE. W.H. also acknowledges the support from the National Natural Science Foundation of China (grant no. 21303153). The authors deeply appreciate Dr Michael F. Santillo's critical review of the paper. NR 97 TC 29 Z9 30 U1 5 U2 55 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 2014 VL 22 IS 1 SI SI BP 49 EP 63 DI 10.1016/j.jfda.2014.01.004 PG 15 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AE3CH UT WOS:000333854100005 PM 24673903 ER PT J AU Fu, PP Xia, QS Hwang, HM Ray, PC Yu, HT AF Fu, Peter P. Xia, Qingsu Hwang, Huey-Min Ray, Paresh C. Yu, Hongtao TI Mechanisms of nanotoxicity: Generation of reactive oxygen species SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE Lipid peroxidation; Nanotoxicology; Reactive oxygen species ID TITANIUM-DIOXIDE NANOPARTICLES; METAL-OXIDE NANOPARTICLES; HACAT KERATINOCYTES-GENERATION; BRONCHIAL EPITHELIAL-CELLS; HUMAN SKIN KERATINOCYTES; INDUCE OXIDATIVE STRESS; DNA-DAMAGE; FREE-RADICALS; LIPID-PEROXIDATION; SINGLET OXYGEN AB Nanotechnology is a rapidly developing field in the 21st century, and the commercial use of nanomaterials for novel applications is increasing exponentially. To date, the scientific basis for the cytotoxicity and genotoxicity of most manufactured nanomaterials are not understood. The mechanisms underlying the toxicity of nanomaterials have recently been studied intensively. An important mechanism of nanotoxicity is the generation of reactive oxygen species (ROS). Overproduction of ROS can induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions. This in turn leads to DNA damage, unregulated cell signaling, change in cell motility, cytotoxicity, apoptosis, and cancer initiation. There are critical determinants that can affect the generation of ROS. These critical determinants, discussed briefly here, include: size, shape, particle surface, surface positive charges, surface-containing groups, particle dissolution, metal ion release from nanometals and nanometal oxides, UV light activation, aggregation, mode of interaction with cells, inflammation, and pH of the medium. Copyright (C) 2014, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Fu, Peter P.; Xia, Qingsu] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hwang, Huey-Min] Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. [Ray, Paresh C.; Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov RI Geracitano, Laura/E-6926-2013 NR 144 TC 81 Z9 81 U1 31 U2 148 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 2014 VL 22 IS 1 SI SI BP 64 EP 75 DI 10.1016/j.jfda.2014.01.005 PG 12 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AE3CH UT WOS:000333854100006 PM 24673904 ER PT J AU Li, M Yin, JJ Wamer, WG Lo, YM AF Li, Meng Yin, Jun-Jie Wamer, Wayne G. Lo, Y. Martin TI Mechanistic characterization of titanium dioxide nanoparticle-induced toxicity using electron spin resonance SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE Electron spin resonance; Reactive oxygen species; Titanium dioxide nanoparticles ID HACAT KERATINOCYTES-GENERATION; PROTEIN RADICAL FORMATION; OXIDATIVE DNA-DAMAGE; SINGLET OXYGEN; TIO2 NANOPARTICLES; VISIBLE-LIGHT; IN-VITRO; PARAMAGNETIC-RESONANCE; BACTERICIDAL ACTIVITY; LIPID-PEROXIDATION AB Titanium dioxide nanoparticles (TiO2 NPs) are one of the most widely used nanomaterials that have been manufactured worldwide and applied in different commercial realms. The well-recognized ability of TiO2 to promote the formation of reactive oxygen species (ROS) has been extensively studied as one of the important mechanisms underlying TiO2 NPs toxicity. As the "gold standard" method to quantify and identify ROS, electron spin resonance (ESR) spectroscopy has been employed in many studies aimed at evaluating TiO2 NPs safety. This review aims to provide a thorough discussion of current studies using ESR as the primary method to unravel the mechanism of TiO2 NPs toxicity. ESR spin label oximetry and immune-spin trapping techniques are also briefly introduced, because the combination of spin trapping/labeling techniques offers a promising tool for studying the oxidative damage caused by TiO2 NPs. Copyright (C) 2014, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Li, Meng; Yin, Jun-Jie; Wamer, Wayne G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Li, Meng; Lo, Y. Martin] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Lo, YM (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM ymlo@umd.edu RI Yin, Jun Jie /E-5619-2014 FU Chinese Scholarship Council FX The authors thank the Chinese Scholarship Council for providing a scholarship to M.Li for her PhD studies at the University of Maryland, College Park, MD, USA. NR 75 TC 7 Z9 7 U1 3 U2 46 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 2014 VL 22 IS 1 SI SI BP 76 EP 85 DI 10.1016/j.jfda.2014.01.006 PG 10 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AE3CH UT WOS:000333854100007 PM 24673905 ER PT J AU Wu, HH Yin, JJ Wamer, WG Zeng, MY Lo, YM AF Wu, Haohao Yin, Jun-Jie Wamer, Wayne G. Zeng, Mingyong Lo, Y. Martin TI Reactive oxygen species-related activities of nano-iron metal and nano-iron oxides SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE Iron oxide; Metallic iron; Nanoparticle; Reactive oxygen species; Toxicity ID HYDROGEN-PEROXIDE DECOMPOSITION; ZERO-VALENT IRON; HYDROXYL RADICALS; FENTON REACTION; CATALYZED OXIDATION; MEDIATED PRODUCTION; PARTICLE-SIZE; NANOPARTICLES; DEGRADATION; HEMATITE AB Nano-iron metal and nano-iron oxides are among the most widely used engineered and naturally occurring nanostructures, and the increasing incidence of biological exposure to these nanostructures has raised concerns about their biotoxicity. Reactive oxygen species (ROS)-induced oxidative stress is one of the most accepted toxic mechanisms and, in the past decades, considerable efforts have been made to investigate the ROS-related activities of iron nanostructures. In this review, we summarize activities of nano-iron metal and nano-iron oxides in ROS-related redox processes, addressing in detail the known homogeneous and heterogeneous redox mechanisms involved in these processes, intrinsic ROS-related properties of iron nanostructures (chemical composition, particle size, and crystalline phase), and ROS-related bio-microenvironmental factors, including physiological pH and buffers, biogenic reducing agents, and other organic substances. Copyright (C) 2014, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Wu, Haohao; Zeng, Mingyong] Ocean Univ China, Coll Food Sci & Engn, Qingdao 266003, Shandong, Peoples R China. [Wu, Haohao; Lo, Y. Martin] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Wu, Haohao; Yin, Jun-Jie; Wamer, Wayne G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM junjie.yin@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014; OI Zeng, Mingyong/0000-0002-3580-9139; Wu, Haohao/0000-0003-3852-2608 FU China Scholarship Council (CSC) [201306330015] FX The financial support of the China Scholarship Council (CSC; No. 201306330015) is gratefully acknowledged. NR 74 TC 23 Z9 24 U1 10 U2 93 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 2014 VL 22 IS 1 SI SI BP 86 EP 94 DI 10.1016/j.jfda.2014.01.007 PG 9 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AE3CH UT WOS:000333854100008 PM 24673906 ER PT J AU Chen, T Yan, J Li, Y AF Chen, Tao Yan, Jian Li, Yan TI Genotoxicity of titanium dioxide nanoparticles SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE Ames test; Carcinogenicity; Comet; Genotoxicity; Hypoxanthine-guanine phosphoribosyl transferase gene; Micronucleus; Phosphatidylinositol glycan; Class A gene; Sister chromatid exchange; Titanium dioxide nanoparticles; Wing point mutation ID PERIPHERAL-BLOOD LYMPHOCYTES; IN-VITRO CYTOTOXICITY; TIO2 NANOPARTICLES; OXIDATIVE STRESS; DNA-DAMAGE; VIVO GENOTOXICITY; COMET ASSAY; CELLS; PARTICLES; APOPTOSIS AB Titanium dioxide nanoparticles (TiO2-NP5, <100 nm) are increasingly being used in pharmaceuticals and cosmetics due to the unique properties derived from their small sizes. However, their large surface-area to mass ratio and high redox potential may negatively impact human health and the environment. TiO2-NPs can cause inflammation, pulmonary damage, fibrosis, and lung tumors and they are possibly carcinogenic to humans. Because cancer is a disease involving mutation, there are a large number of studies on the genotoxicity of TiO2-NPs. In this article, we review the results that have been reported in the literature, with a focus on data generated from the standard genotoxicity assays. The data include genotoxicity results from the Ames test, in vitro and in vivo Comet assay, in vitro and in vivo micronucleus assay, sister chromatid exchange assay, mammalian cell hypoxanthine-guanine phosphoribosyl transferase gene assay, the wing somatic mutation and recombination assay, and the mouse phosphatidylinositol glycan, class A gene assay. Inconsistent results have been found in these assays, with both positive and negative responses being reported. The in vitro systems for assessing the genotoxicity of TiO2-NP5 have generated a greater number of positive results than the in vivo systems, and tests for DNA and chromosome damage have produced more positive results than the assays measuring gene mutation. Nearly all tests for measuring the mutagenicity of TiO2-NP5 were negative. The current data indicate that the genotoxicity of TiO2-NPs is mediated mainly through the generation of oxidative stress in cells. Copyright (C) 2014, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Chen, Tao; Yan, Jian; Li, Yan] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, T (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov NR 51 TC 28 Z9 30 U1 7 U2 56 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 2014 VL 22 IS 1 SI SI BP 95 EP 104 DI 10.1016/j.jfda.2014.01.008 PG 10 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AE3CH UT WOS:000333854100009 PM 24673907 ER PT J AU Guo, XQ Mei, N AF Guo, Xiaoqing Mei, Nan TI Assessment of the toxic potential of graphene family nanomaterials SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE Functionalization; Genotoxicity; Graphene; Graphene oxide; Reduced graphene oxide; Toxicity ID WALLED CARBON NANOTUBES; MS/MS PROTEOME ANALYSIS; HEPATOMA HEPG2 CELLS; DRUG-DELIVERY; FUNCTIONALIZED GRAPHENE; PHOTOTHERMAL THERAPY; OXIDE NANOSHEETS; NANO-GRAPHENE; IN-VITRO; CAENORHABDITIS-ELEGANS AB Graphene, a single-atom-thick carbon nanosheet, has attracted great interest as a promising nanomaterial for a variety of bioapplications because of its extraordinary properties. However, the potential for widespread human exposure raises safety concerns about graphene and its derivatives, referred to as graphene-family nanomaterials. This review summarizes recent findings on the toxicological effects and the potential toxicity mechanisms of graphene-family nanomaterials in bacteria, mammalian cells, and animal models. Graphene, graphene oxide, and reduced graphene oxide elicit toxic effects both in vitro and in vivo, whereas surface modifications can significantly reduce their toxic interactions with living systems. Standardization of terminology and the fabrication methods of graphene-family nanomaterials are warranted for further investigations designed to decrease their adverse effects and explore their biomedical applications. Copyright (C) 2014, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Guo, Xiaoqing; Mei, Nan] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. RP Guo, XQ (reprint author), Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM xiaoqing.guo@fda.hhs.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 99 TC 55 Z9 54 U1 20 U2 175 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 2014 VL 22 IS 1 SI SI BP 105 EP 115 DI 10.1016/j.jfda.2014.01.009 PG 11 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AE3CH UT WOS:000333854100010 PM 24673908 ER PT J AU Karmakar, A Zhang, QL Zhang, YB AF Karmakar, Alokita Zhang, Qinli Zhang, Yongbin TI Neurotoxicity of nanoscale materials SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE Blood-brain barrier; Nanomaterial; Neurotoxicity; Oxidative stress ID BLOOD-BRAIN-BARRIER; TITANIUM-DIOXIDE NANOPARTICLES; METAL-OXIDE NANOPARTICLES; CENTRAL-NERVOUS-SYSTEM; MICROVESSEL ENDOTHELIAL-CELLS; SPRAGUE-DAWLEY RATS; SILVER NANOPARTICLES; OXIDATIVE STRESS; ZINC-OXIDE; IN-VITRO AB Nanotechnology has been applied in consumer products and commercial applications, showing a significant impact on almost all industries and all areas of society. Significant evidence indicates that manufactured nanomaterials and combustion-derived nanomaterials elicit toxicity in humans exposed to these nanomaterials. The interaction of the engineered nanomaterials with the nervous system has received much attention in the nanotoxicology field. In this review, the biological effects of metal, metal oxide, and carbon-based nanomaterials on the nervous system are discussed from both in vitro and in vivo studies. The translocation of the nanoparticles through the blood brain barrier or nose to brain via the olfactory bulb route, oxidative stress, and inflammatory mechanisms of nanomaterials are also reviewed. Copyright (C) 2014, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved. C1 [Karmakar, Alokita; Zhang, Yongbin] US FDA, Nanotechnol Core Facil, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Zhang, Qinli] Shanxi Med Univ, Sch Publ Hlth, Taiyuan 030001, Peoples R China. RP Zhang, YB (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM yongbin.zhang@fda.hhs.gov RI Geracitano, Laura/E-6926-2013 NR 156 TC 23 Z9 24 U1 4 U2 69 PU FOOD & DRUG ADMINSTRATION PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 2014 VL 22 IS 1 SI SI BP 147 EP 160 DI 10.1016/j.jfda.2014.01.012 PG 14 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA AE3CH UT WOS:000333854100013 PM 24673911 ER PT J AU Hur, J Liu, ZC Tong, WD Laaksonen, R Bai, JPF AF Hur, Junguk Liu, Zhichao Tong, Weida Laaksonen, Reijo Bai, Jane P. F. TI Drug-Induced Rhabdomyolysis: From Systems Pharmacology Analysis to Biochemical Flux SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID STATIN-INDUCED MYOPATHY; II DEFICIENCY; MITOCHONDRIAL-FUNCTION; GENETIC RISK; MUSCLE; SIMVASTATIN; DISEASE; ASSOCIATION; RECEPTORS; DISCOVERY AB The goal of this study was to integrate systems pharmacology and biochemical flux to delineate drug-induced rhabdomyolysis by leveraging prior knowledge and publicly accessible data. A list of 211 rhabdomyolysis-inducing drugs (RIDs) was compiled and curated from multiple sources. Extended pharmacological network analysis revealed that the intermediators directly interacting with the pharmacological targets of RIDs were significantly enriched with functions such as regulation of cell cycle, apoptosis, and ubiquitin-mediated proteolysis. A total of 78 intermediators were shown to be significantly connected to at least five RIDs, including estrogen receptor 1 (ESR1), synuclein gamma (SNCG), and janus kinase 2 (JAK2). Transcriptomic analysis of RIDs profiled in Connectivity Map on the global scale revealed that multiple pathways are perturbed by RIDs, including ErbB signaling and lipid metabolism pathways, and that carnitine palmitoyl transferase 2 (CPT2) was in the top 1 percent of the most differentially perturbed genes. CPT2 was downregulated by nine drugs that perturbed the genes significantly enriched in oxidative phosphorylation and energy-metabolism pathways. With statins as the use case, biochemical pathway analysis on the local scale implicated a role for CPT2 in statin-induced perturbation of energy homeostasis, which is in agreement with reports of statin CPT2 interaction. Considering the complexity of human biology, an integrative multiple-approach analysis composed of a biochemical flux network, pharmacological on- and off-target networks, and transcriptomic signature is important for understanding drug safety and for providing insight into clinical gene drug interactions. C1 [Hur, Junguk] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Hur, Junguk; Bai, Jane P. F.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Liu, Zhichao; Tong, Weida] US FDA, Div Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Liu, Zhichao; Tong, Weida] US FDA, Div Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Laaksonen, Reijo] Univ Tampere, Sch Med, Tampere 33520, Finland. RP Bai, JPF (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM jane.bai@fda.hhs.gov RI Liu, Zhichao/C-4035-2011; OI Hur, Junguk/0000-0002-0736-2149 FU Critical Path Grant from the Center for Drug Evaluation and Research; Juvenile Diabetes Research Foundation FX Part of this study was supported by a Critical Path Grant from the Center for Drug Evaluation and Research to J.B. and by a Postdoctoral Fellowship from the Juvenile Diabetes Research Foundation to J.H. NR 39 TC 5 Z9 5 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X EI 1520-5010 J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2014 VL 27 IS 3 SI SI BP 421 EP 432 DI 10.1021/tx400409c PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA AD3MH UT WOS:000333142700011 PM 24422454 ER PT J AU Plaut, RD Beaber, JW Zemansky, J Kaur, AP George, M Biswas, B Henry, M Bishop-Lilly, KA Mokashi, V Hannah, RM Pope, RK Read, TD Stibitz, S Calendar, R Sozhamannan, S AF Plaut, Roger D. Beaber, John W. Zemansky, Jason Kaur, Ajinder P. George, Matroner Biswas, Biswajit Henry, Matthew Bishop-Lilly, Kimberly A. Mokashi, Vishwesh Hannah, Ryan M. Pope, Robert K. Read, Timothy D. Stibitz, Scott Calendar, Richard Sozhamannan, Shanmuga TI Genetic Evidence for the Involvement of the S-Layer Protein Gene sap and the Sporulation Genes spo0A, spo0B, and spo0F in Phage AP50c Infection of Bacillus anthracis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MOLECULAR CHARACTERIZATION; WALL POLYSACCHARIDE; ESCHERICHIA-COLI; CEREUS; CELL; SUBTILIS; THURINGIENSIS; ADSORPTION; BACTERIA; PLASMID AB In order to better characterize the Bacillus anthracis typing phage AP50c, we designed a genetic screen to identify its bacterial receptor. Insertions of the transposon mariner or targeted deletions of the structural gene for the S-layer protein Sap and the sporulation genes spo0A, spo0B, and spo0F in B. anthracis Sterne resulted in phage resistance with concomitant defects in phage adsorption and infectivity. Electron microscopy of bacteria incubated with AP50c revealed phage particles associated with the surface of bacilli of the Sterne strain but not with the surfaces of Delta sap, Delta spo0A, Delta spo0B, or Delta spo0F mutants. The amount of Sap in the S layer of each of the spo0 mutant strains was substantially reduced compared to that of the parent strain, and incubation of AP50c with purified recombinant Sap led to a substantial reduction in phage activity. Phylogenetic analysis based on wholegenome sequences of B. cereus sensu lato strains revealed several closely related B. cereus and B. thuringiensis strains that carry sap genes with very high similarities to the sap gene of B. anthracis. Complementation of the Delta sap mutant in trans with the wildtype B. anthracis sap or the sap gene from either of two different B. cereus strains that are sensitive to AP50c infection restored phage sensitivity, and electron microscopy confirmed attachment of phage particles to the surface of each of the complemented strains. Based on these data, we postulate that Sap is involved in AP50c infectivity, most likely acting as the phage receptor, and that the spo0 genes may regulate synthesis of Sap and/or formation of the S layer. C1 [Plaut, Roger D.; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Beaber, John W.; Zemansky, Jason; Calendar, Richard] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Kaur, Ajinder P.; George, Matroner; Biswas, Biswajit; Henry, Matthew; Bishop-Lilly, Kimberly A.; Sozhamannan, Shanmuga] Henry M Jackson Fdn, Bethesda, MD USA. [Kaur, Ajinder P.; George, Matroner; Biswas, Biswajit; Henry, Matthew; Bishop-Lilly, Kimberly A.; Mokashi, Vishwesh; Sozhamannan, Shanmuga] NMRC Frederick, Biol Def Res Directorate, Naval Med Res Ctr, Ft Detrick, MD USA. [Hannah, Ryan M.; Pope, Robert K.] Natl Biodefense Anal & Countermeasures Ctr, Ft Detrick, MD USA. [Read, Timothy D.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA. [Read, Timothy D.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. RP Plaut, RD (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM Roger.Plaut@fda.hhs.gov RI Plaut, Roger/B-2340-2013 OI Plaut, Roger/0000-0002-0883-972X FU Defense Threat Reduction Agency, U.S. Department of Defense, of the U.S. government [8.10084_ 08_ NM_ B]; U.S. Department of Homeland Security (DHS) [HSHQDC-07-C-00020] FX This work was supported by funds from the Defense Threat Reduction Agency, U.S. Department of Defense, of the U.S. government (proposal no. 8.10084_ 08_ NM_ B) to S. Sozhamannan. R.K. Pope and R.M. Hannah were funded under agreement no. HSHQDC-07-C-00020 awarded by the U.S. Department of Homeland Security (DHS) for the management and operation of the National Biodefense Analysis and Counter-measures Center (NBACC), a federally funded research and development center. NR 71 TC 3 Z9 3 U1 1 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2014 VL 196 IS 6 BP 1143 EP 1154 DI 10.1128/JB.00739-13 PG 12 WC Microbiology SC Microbiology GA AC6JO UT WOS:000332628700002 PM 24363347 ER PT J AU Sundh, F Simlund, J Harrison, JK Maynard, C Ugander, M Strauss, DG Carlsen, E Wagner, GS AF Sundh, Frida Simlund, Jacob Harrison, J. Kevin Maynard, Charles Ugander, Martin Strauss, David G. Carlsen, Esben Wagner, Galen S. TI Impact of ostium secundum atrial septal defect closure on the resolution of falsely positive electrocardiographic criteria for myocardial scarring SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 40th International Congress on Electrocardiology (ICE) CY AUG 04-07, 2013 CL Glasgow, SCOTLAND DE Atrial septal defect; Anterior infarct criteria; RV volume overload; Electrocardiogram ID VENTRICULAR VOLUME OVERLOAD; PULMONARY-HYPERTENSION; TRANSCATHETER CLOSURE; HEART; ADULTS; SIZE; ECG AB Background: Electrocardiographic (ECG) Selvester QRS score criteria with false indication of anteroseptal scarring consistent with myocardial infarction have been found in patients with ostium secundum atrial septal defect (OS-ASD). The objective of this study was to evaluate ECGs pre and post percutaneous transcatheter OS-ASD closure to test the hypothesis that the falsely positive criteria for anteroseptal scar decline 1 day post procedure. Methods: Patients (n = 34, mean age 48 +/- 17 years, 79% female) that underwent OS-ASD closure and had undergone pre procedure cardiac magnetic resonance imaging showing no left ventricular (LV) scarring were included in this study. ECGs pre and 1 day post procedure were assessed according to the QRS Selvester scoring system and compared. Results: Mean Selvester score in anteroseptal regions pre procedure was 6.6 (0.0-6.8) % LV scar and decreased to 4.3 (0.0-6.0) % LV scar one day after the procedure (p = 0.01). Mean Selvester score in lateral regions pre procedure was 3.7 (0.0-3.0) %LV scar and decreased to 2.8 (0.0-0.0) % LV scar one day post procedure (p = 0.25). Discussion: OS-ASD patients with falsely positive anteroseptal scar criteria by the Selvester QRS score pre procedure have a significant decrease in anteroseptal Selvester score 1 day post procedure. The falsely positive anteroseptal scar criteria did not completely resolve 1 day post procedure. Further studies are needed to investigate the relationship between ECG criteria for anteroseptal scar and right ventricular volume overload in late follow up. (C) 2014 Published by Elsevier Inc. C1 [Sundh, Frida; Simlund, Jacob; Ugander, Martin] Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden. [Sundh, Frida; Simlund, Jacob; Ugander, Martin] Karolinska Univ Hosp, Stockholm, Sweden. [Sundh, Frida; Simlund, Jacob; Wagner, Galen S.] Duke Clin Res Inst, Durham, NC USA. [Harrison, J. Kevin] Duke Univ, Div Cardiol, Sch Med, Durham, NC 27705 USA. [Maynard, Charles] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Carlsen, Esben] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. RP Wagner, GS (reprint author), Duke Univ, Med Ctr, 2400 Pratt St, Durham, NC 27705 USA. EM galen.wagner@duke.edu RI Maynard, Charles/N-3906-2015; OI Maynard, Charles/0000-0002-1644-7814; Ugander, Martin/0000-0003-3665-2038 NR 18 TC 3 Z9 3 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAR-APR PY 2014 VL 47 IS 2 BP 197 EP 201 DI 10.1016/j.jelectrocard.2013.11.005 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD7IW UT WOS:000333438400012 PM 24491675 ER PT J AU Fillingim, RB Bruehl, S Dworkin, RH Dworkin, SF Loeser, JD Turk, DC Widerstrom-Noga, E Arnold, L Bennett, R Edwards, RR Freeman, R Gewandter, J Hertz, S Hochberg, M Krane, E Mantyh, PW Markman, J Neogi, T Ohrbach, R Paice, JA Porreca, F Rappaport, BA Smith, SM Smith, TJ Sullivan, MD Verne, GN Wasan, AD Wesselmann, U AF Fillingim, Roger B. Bruehl, Stephen Dworkin, Robert H. Dworkin, Samuel F. Loeser, John D. Turk, Dennis C. Widerstrom-Noga, Eva Arnold, Lesley Bennett, Robert Edwards, Robert R. Freeman, Roy Gewandter, Jennifer Hertz, Sharon Hochberg, Marc Krane, Elliot Mantyh, Patrick W. Markman, John Neogi, Tuhina Ohrbach, Richard Paice, Judith A. Porreca, Frank Rappaport, Bob A. Smith, Shannon M. Smith, Thomas J. Sullivan, Mark D. Verne, G. Nicholas Wasan, Ajay D. Wesselmann, Ursula TI The ACTTION-American Pain Society Pain Taxonomy (AAPT): An Evidence-Based and Multidimensional Approach to Classifying Chronic Pain Conditions SO JOURNAL OF PAIN LA English DT Article DE Taxonomy; chronic pain; pain classification; biopsychosocial; evidence-based; mechanism-based pain classification ID INTERNATIONAL CLASSIFICATION; HEADACHE DISORDERS; OSTEOARTHRITIS; DEPRESSION; PERCEPTION; MECHANISMS AB Current approaches to classification of chronic pain conditions suffer from the absence of a systematically implemented and evidence-based taxonomy. Moreover, existing diagnostic approaches typically fail to incorporate available knowledge regarding the biopsychosocial mechanisms contributing to pain conditions. To address these gaps, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration and the American Pain Society (APS) have joined together to develop an evidence-based chronic pain classification system called the ACTTION-APS Pain Taxonomy. This paper describes the outcome of an ACTTION-APS consensus meeting, at which experts agreed on a structure for this new taxonomy of chronic pain conditions. Several major issues around which discussion revolved are presented and summarized, and the structure of the taxonomy is presented. ACTTION-APS Pain Taxonomy will include the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors. In coming months, expert working groups will apply this taxonomy to clusters of chronic pain conditions, thereby developing a set of diagnostic criteria that have been consistently and systematically implemented across nearly all common chronic pain conditions. It is anticipated that the availability of this evidence-based and mechanistic approach to pain classification will be of substantial benefit to chronic pain research and treatment. Perspective: The ACTTION-APS Pain Taxonomy is an evidence-based chronic pain classification system designed to classify chronic pain along the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors. (C) 2014 by the American Pain Society C1 [Fillingim, Roger B.] Pain Res & Intervent Ctr Excellence, Gainesville, FL USA. [Bruehl, Stephen] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA. [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Neurol, Ctr Human Expt Therapeut, Rochester, NY USA. [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Anesthet & Addict Clin Trial Translat Innovat Opp, Rochester, NY USA. [Dworkin, Samuel F.] Univ Washington, Sch Dent, Dept Psychiat & Behav Sci, Sch Med,Dept Oral Med, Seattle, WA 98195 USA. [Loeser, John D.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA USA. [Widerstrom-Noga, Eva] Univ Miami, Miller Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA. [Arnold, Lesley] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [Arnold, Lesley] Univ Cincinnati, Coll Med, Womens Hlth Res Program, Cincinnati, OH USA. [Bennett, Robert] Oregon Hlth & Sci Univ, Fibromyalgia Res Unit, Portland, OR 97201 USA. [Edwards, Robert R.] Brigham & Womens Hosp, Chestnut Hill, MA USA. [Freeman, Roy] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Gewandter, Jennifer; Smith, Shannon M.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY USA. [Hertz, Sharon; Rappaport, Bob A.] Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hochberg, Marc] Univ Maryland, Sch Med, Dept Med, Div Rheumatol & Clin Immunol, Baltimore, MD 21201 USA. [Krane, Elliot] Stanford Univ, Dept Anesthesiol, Stanford, CA 94305 USA. [Krane, Elliot] Stanford Univ, Dept Perioperat, Stanford, CA 94305 USA. [Krane, Elliot] Stanford Univ, Dept Pain Med, Stanford, CA 94305 USA. [Mantyh, Patrick W.; Porreca, Frank] Univ Arizona, Dept Pharmacol, Tucson, AZ USA. [Markman, John] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. [Neogi, Tuhina] Clin Epidemiol Unit, Boston, MA USA. [Ohrbach, Richard] Univ Buffalo, Dept Oral Diagnost Sci, Buffalo, NY USA. [Paice, Judith A.] Northwestern Univ, Canc Pain Program, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA. [Smith, Thomas J.] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA. [Smith, Thomas J.] Johns Hopkins Univ Hosp, Johns Hopkins Med Inst, Baltimore, MD 21287 USA. [Sullivan, Mark D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Verne, G. Nicholas] Univ Texas Med Branch, Dept Med, Galveston, TX 77555 USA. [Wasan, Ajay D.] Univ Pittsburgh, Dept Anesthesiol & Psychiat, Pittsburgh, PA USA. [Wesselmann, Ursula] Univ Alabama Birmingham, Dept Anesthesiol & Neurol, Birmingham, AL USA. RP Fillingim, RB (reprint author), Univ Florida, Coll Dent, UF Pain Res & Intervent Ctr Excellence Clin & Tra, Room 3216,2004 Mowry Rd,POB 100404, Gainesville, FL 32610 USA. EM rfilling@ufl.edu OI Paice, Judith/0000-0001-7534-1756; Bennett, Robert/0000-0002-7526-3425; Neogi, Tuhina/0000-0002-9515-1711 FU ACTTION; U.S. Food and Drug Administration (FDA) FX The views expressed in this article are those of the authors, none of whom has a financial conflict of interest related to the specific issues discussed in this manuscript. All of the authors attended the consensus meeting on which this article is based. In addition, the consensus meeting was attended by employees of Pfizer, one of the companies that provided unrestricted grants to ACTTION to support its activities. However, these individuals did not contribute to the content of this manuscript. No official endorsement by the U.S. Food and Drug Administration (FDA) or the pharmaceutical companies that have provided unrestricted grants to support the activities of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the FDA should be inferred. The consensus meeting on which this article is based was funded by ACTTION, which has received research grants or other revenue from the FDA, various pharmaceutical companies, and other sources. NR 25 TC 28 Z9 28 U1 0 U2 13 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD MAR PY 2014 VL 15 IS 3 BP 241 EP 249 DI 10.1016/j.jpain.2014.01.004 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AD7IQ UT WOS:000333437800005 PM 24581634 ER PT J AU Chaudhury, A Barrasso, D Pandey, P Wu, HQ Ramachandran, R AF Chaudhury, Anwesha Barrasso, Dana Pandey, Preetanshu Wu, Huiquan Ramachandran, Rohit TI Population Balance Model Development, Validation, and Prediction of CQAs of a High-Shear Wet Granulation Process: Towards QbD in Drug Product Pharmaceutical Manufacturing SO JOURNAL OF PHARMACEUTICAL INNOVATION LA English DT Article DE Granulation; Multidimensional population balance model; QbD; Predictive modeling; Multiobjective optimization; Particle size distribution ID LIQUID-BOUND GRANULES; NUCLEATION REGIME MAP; PROCESS SYSTEMS; PARAMETERS; KINETICS; PARTICLE; GROWTH; AGGLOMERATION; FORMULATION; BREAKAGE AB This paper focuses on the predictive model development for a pharmaceutically relevant model granulation process. A population balance modeling (PBM) framework has been employed for modeling purposes which is then utilized to obtain accurate predictions of the process. The model is aligned to adequately describe the high-shear mode of granulation operation in a batch process. The model is calibrated using the particle swarm algorithm (PSA) in the form of a multiobjective optimization problem. The multiobjective optimization problem was implemented based on the epsilon-constraint method which involves the handling of multiple cost functions in the form of constraints with the minimization of one primary objective function from the entire set of cost functions. The resultant solutions obtained from the model are Pareto optimal. The effects of the impeller speed, liquid-to-solid ratio, and wet massing time on the particle size distributions were characterized, and predicted size distributions were in agreement with experimental results. The predictive model framework lends itself to the quality by design (QbD) initiative undertaken by the US Food and Drug Administration (US FDA). C1 [Chaudhury, Anwesha; Barrasso, Dana; Ramachandran, Rohit] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08854 USA. [Pandey, Preetanshu] Bristol Myers Squibb, Drug Prod Sci & Technol, New Brunswick, NJ USA. [Wu, Huiquan] US FDA, Div Prod Qual Res HFD 940, Off Testing & Res, Off Pharmaceut Sci,CDER, Silver Spring, MD USA. RP Ramachandran, R (reprint author), Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08854 USA. EM rohit.r@rutgers.edu FU National Institute for Pharmaceutical Technology and Education (NIPTE); US Food and Drug Administration (FDA); FDA [5U01FD004275-02]; National Science Foundation Engineering Research Center on Structured Organic Particulate Systems [NSF-ECC 0540855] FX We are grateful to the National Institute for Pharmaceutical Technology and Education (NIPTE) and the US Food and Drug Administration (FDA) for providing funds for this research. This study was funded by the FDA-sponsored Grant "Critical Path Manufacturing Sector Research Initiative (5U01FD004275-02)." This work was also supported by the National Science Foundation Engineering Research Center on Structured Organic Particulate Systems, via Grant NSF-ECC 0540855. The authors also thank Dilbir Bindra and Jing Tao from Bristol-Myers Squibb for their contributions to this work. The support from various FDA managers including Dr. Mansoor Khan, Dr. Richard Lostritto, Dr. Vincent Vilker, and Mr. Jon E. Clark, and insightful FDA internal review by Dr. Cindy Buhse are acknowledged. NR 37 TC 7 Z9 7 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1872-5120 EI 1939-8042 J9 J PHARM INNOV JI J. Pharm. Innov. PD MAR PY 2014 VL 9 IS 1 BP 53 EP 64 DI 10.1007/s12247-014-9172-7 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AD3ON UT WOS:000333155600006 ER PT J AU Idelson, C Vogt, W Rylander, C AF Idelson, Christopher Vogt, William Rylander, Christopher TI EFFECT OF MECHANICAL OPTICAL CLEARING ON NEAR-INFRARED SPECTROSCOPY SIGNAL SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 Virginia Tech, Sch Biomed Engn & Sci, Blacksburg, VA USA. US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 108 BP 36 EP 36 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800101 ER PT J AU Murthy, S Rizzi, P Mewton, N Strauss, DG Liu, CY Volpe, GJ Marchlinski, FE Spooner, P Berger, RD Kellman, P Lima, JAC Tereshchenko, LG AF Murthy, Sindhoora Rizzi, Patricia Mewton, Nathan Strauss, David G. Liu, Chia Y. Volpe, Gustavo Jardim Marchlinski, Francis E. Spooner, Peter Berger, Ronald D. Kellman, Peter Lima, Joao A. C. Tereshchenko, Larisa G. TI Number of P- Wave Fragmentations on P- SAECG Correlates with Infiltrated Atrial Fat SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE atrial fibrillation; P-SAECG; cardiac magnetic resonance; infiltrated atrial fat ID EPICARDIAL ADIPOSE-TISSUE; SIGNAL-AVERAGED ECG; PERICARDIAL FAT; SINUS RHYTHM; FIBRILLATION; RISK; DURATION; HEART; MYOCARDIUM; PREDICTION AB BackgroundAlthough atrial fibrillation (AF) triggers are known, the underlying AF substrate is less well understood. The goal of our study was to explore correlations between electrophysiological and structural characteristics of atria in patients with paroxysmal AF and individuals at AF risk. MethodsPatients in sinus rhythm (N = 90; age 57 10 year; 55 men [63.2%]) with structural heart disease and paroxysmal AF (n = 12 [13%]), or with AF risk factors and LVEF > 35% (n = 78), underwent SAECG and cardiac magnetic resonance study. Interatrial and epicardial fat was analyzed with a Dark-blood DIR-prepared Fat-Water-separated sequence in the horizontal longitudinal axis. All local P-wave extrema were identified on SAECG leads during sinus rhythm. A P-wave fragmentation (P-f) was defined as an absolute difference between adjacent extrema which was above three standard deviations of noise, and was normalized by the duration of the P wave in the corresponding lead. ResultsThe P-f was greater on the filtered than on the unfiltered P-SAECG signal (13.1 +/- 3.8 vs. 3.4 +/- 1.2; P < 0.0001). P-f was the greatest on the Y lead (13.0 +/- 3.5 on Y lead vs. 12.1 +/- 3.4 on Z lead; P = 0.003. P-f on Z lead correlated with interatrial fat index (r = 0.544; P = 0.001). Epicardial fat significantly correlated with body mass index (BMI; r = 0.302; P = 0.015). After adjustment for BMI, left atrium (LA) size, epicardial fat, and interatrial septum width, interatrial fat independently associated with the P-f on Z lead (-coefficient 0.009 [95%CI 0.0003-0.019]; P = 0.043). ConclusionsInfiltrated atrial fat correlates with discontinuous conduction on posterior LA wall and represents AF early substrate. C1 [Murthy, Sindhoora] Johns Hopkins Univ, Whiting Sch Engn, Baltimore, MD USA. [Rizzi, Patricia; Mewton, Nathan; Liu, Chia Y.; Volpe, Gustavo Jardim; Spooner, Peter; Berger, Ronald D.; Lima, Joao A. C.; Tereshchenko, Larisa G.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Strauss, David G.] US FDA, Silver Spring, MD USA. [Marchlinski, Francis E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Kellman, Peter] NHLBI, NIH, Bethesda, MD 20892 USA. RP Tereshchenko, LG (reprint author), Carnegie 568,600 N Wolfe St, Baltimore, MD 21287 USA. EM lteresh1@jhmi.edu OI Marchlinski, Francis/0000-0001-7962-9423; Tereshchenko, Larisa/0000-0002-6976-1313 FU Cardiac Translational Research Implementation Program (C-TRIP); NIH/National Heart, Lung and Blood Institute [P20HL101397]; Leducq Foundation FX Financial support & relationships with industry: Study was partially supported by Cardiac Translational Research Implementation Program (C-TRIP) grant from NIH/National Heart, Lung and Blood Institute #P20HL101397 and the Leducq Foundation. NR 39 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1082-720X EI 1542-474X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD MAR PY 2014 VL 19 IS 2 BP 114 EP 121 DI 10.1111/anec.12084 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC6DH UT WOS:000332611100002 PM 24620844 ER PT J AU Crentsil, V Lee, J Jackson, A AF Crentsil, Victor Lee, Jung Jackson, Andre TI Quantitative Drug Benefit-Risk Assessment: Utility of Modeling and Simulation to Optimize Drug Safety in Older Adults SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE geriatric; drug dosing; modeling; simulation; risk-benefit acceptability threshold ID INTERVENTION EFFECTIVENESS CATIE; CLINICAL ANTIPSYCHOTIC TRIALS; POPULATION PHARMACOKINETICS; SCHIZOPHRENIA; OLANZAPINE; PHARMACOLOGY; RISPERIDONE; DISEASE AB Background: More than 50 % of individuals affected by adverse drug events (ADEs) are older adults. Establishing a drug dosing regimen that balances benefit and risk, and minimizes ADEs in older populations can be challenging. Objective: The aim of this study is to evaluate the use of modeling, simulation, and risk-benefit acceptability methods to establish a drug dosing regimen that balances benefit and risk. Methods: The study population comprised nondiabetic patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) >= 50 years old, who had been on oral olanzapine for >= 2 weeks. We used mixed-effects modeling based on a preexisting pharmacokinetic model to derive clearance estimates, which were then used to determine the olanzapine area under the concentration-time curve (AUC). Subsequently, with multivariate regression and Monte Carlo simulation, we estimated the olanzapine dose corresponding to the benefit-risk AUC breakpoint. Results: The study population (n = 34) was predominantly male (82.3%) and white (67.6%), with a mean age of 54.4 years and treatment duration of 361.8 days. The mean AUC was 747.6 ng h/nnL (95% Cl = 524.5, 970.7) for the benefit group (n = 16) and 754.1(95% Cl = 505.9, 1002.4) for the risk group (n = 15). The benefit-risk AUC breakpoint was 524.5 ng h/nnL and the corresponding oral olanzapine dose that optimizes benefit-risk balance was 17.8 mg/d. Conclusions: Our study introduces a real-world approach for finding the safe drug dosing regimen without extensive exposure of a vulnerable and older population to drugs. Further studies into the use of modeling, simulation, and risk-benefit acceptability methods to enhance geriatric drug safety are needed. C1 [Crentsil, Victor; Jackson, Andre] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lee, Jung] Genesis Strateg Solut Inc, Rockville, MD USA. RP Crentsil, V (reprint author), US FDA, Div Psychiat Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM victor.crentsil@fda.hhs.gov FU US FDA CDER Regulatory Science and Review Enhancement (RSR) Program; FDA CDER Critical Path Program FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: US FDA CDER Regulatory Science and Review Enhancement (RSR) Program and the FDA CDER Critical Path Program for the research presented in this article. NR 19 TC 2 Z9 2 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAR PY 2014 VL 48 IS 3 BP 306 EP 313 DI 10.1177/1060028013514376 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AC4NI UT WOS:000332497600001 PM 24473487 ER PT J AU Gould, T Wang, QZ Pfefer, TJ AF Gould, Taylor Wang, Quanzeng Pfefer, T. Joshua TI Optical-thermal light-tissue interactions during photoacoustic breast imaging SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID SENTINEL LYMPH-NODES; PORT-WINE STAINS; IN-VIVO; HUMAN SKIN; BIOLOGICAL TISSUES; OXYGEN-SATURATION; LASER TREATMENT; TOMOGRAPHY; RECONSTRUCTION; BLOOD AB Light-tissue interactions during photoacoustic imaging, including dynamic heat transfer processes in and around vascular structures, are not well established. A three-dimensional, transient, optical-thermal computational model was used to simulate energy deposition, temperature distributions and thermal damage in breast tissue during exposure to pulsed laser trains at 800 and 1064 nm. Rapid and repetitive temperature increases and thermal relaxation led to superpositioning effects that were highly dependent on vessel diameter and depth. For a ten second exposure at established safety limits, the maximum single-pulse and total temperature rise levels were 0.2 degrees C and 5.8 degrees C, respectively. No significant thermal damage was predicted. The impact of tissue optical properties, surface boundary condition and irradiation wavelength on peak temperature location and temperature evolution with time are discussed. (C) 2014 Optical Society of America C1 [Gould, Taylor; Wang, Quanzeng; Pfefer, T. Joshua] Ctr Devices & Radiol Hlth, Food & Drug Adm, Silver Spring, MD 20993 USA. RP Gould, T (reprint author), Ctr Devices & Radiol Hlth, Food & Drug Adm, Silver Spring, MD 20993 USA. EM Joshua.pfefer@fda.hhs.gov NR 62 TC 7 Z9 7 U1 0 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD MAR 1 PY 2014 VL 5 IS 3 BP 832 EP 847 DI 10.1364/BOE.5.000832 PG 16 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AC6YF UT WOS:000332671800015 PM 24688817 ER PT J AU Carr, SA Abbatiello, SE Ackermann, BL Borchers, C Domon, B Deutsch, EW Grant, RP Hoofnagle, AN Huttenhain, R Koomen, JM Liebler, DC Liu, T MacLean, B Mani, D Mansfield, E Neubert, H Paulovich, AG Reiter, L Vitek, O Aebersold, R Anderson, L Bethem, R Blonder, J Boja, E Botelho, J Boyne, M Bradshaw, RA Burlingame, AL Chan, D Keshishian, H Kuhn, E Kinsinger, C Lee, JSH Lee, SW Moritz, R Oses-Prieto, J Rifai, N Ritchie, J Rodriguez, H Srinivas, PR Townsend, RR Van Eyk, J Whiteley, G Wiita, A Weintraub, S AF Carr, Steven A. Abbatiello, Susan E. Ackermann, Bradley L. Borchers, Christoph Domon, Bruno Deutsch, Eric W. Grant, Russell P. Hoofnagle, Andrew N. Huettenhain, Ruth Koomen, John M. Liebler, Daniel C. Liu, Tao MacLean, Brendan Mani, D. R. Mansfield, Elizabeth Neubert, Hendrik Paulovich, Amanda G. Reiter, Lukas Vitek, Olga Aebersold, Ruedi Anderson, Leigh Bethem, Robert Blonder, Josip Boja, Emily Botelho, Julianne Boyne, Michael Bradshaw, Ralph A. Burlingame, Alma L. Chan, Daniel Keshishian, Hasmik Kuhn, Eric Kinsinger, Christopher Lee, Jerry S. H. Lee, Sang-Won Moritz, Robert Oses-Prieto, Juan Rifai, Nader Ritchie, James Rodriguez, Henry Srinivas, Pothur R. Townsend, R. Reid Van Eyk, Jennifer Whiteley, Gordon Wiita, Arun Weintraub, Susan TI Targeted Peptide Measurements in Biology and Medicine: Best Practices for Mass Spectrometry- based Assay Development Using a Fit- for- Purpose Approach SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID DATA-INDEPENDENT ACQUISITION; PROTEIN IDENTIFICATION DATA; EUROPEAN BIOANALYSIS FORUM; LC-MS/MS ASSAY; ISOTOPE-DILUTION; INBORN-ERRORS; ABSOLUTE QUANTIFICATION; QUANTITATIVE PROTEOMICS; CARDIOVASCULAR-DISEASE; BIOMARKER DISCOVERY AB Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on the ability to generate reliable assays that uniquely and confidently identify target peptides in a sample. Unfortunately, there is a wide range of criteria being applied to say that an assay has been successfully developed. There is no consensus on what criteria are acceptable and little understanding of the impact of variable criteria on the quality of the results generated. Publications describing targeted MS assays for peptides frequently do not contain sufficient information for readers to establish confidence that the tests work as intended or to be able to apply the tests described in their own labs. Guidance must be developed so that targeted MS assays with established performance can be made widely distributed and applied by many labs worldwide. To begin to address the problems and their solutions, a workshop was held at the National Institutes of Health with representatives from the multiple communities developing and employing targeted MS assays. Participants discussed the analytical goals of their experiments and the experimental evidence needed to establish that the assays they develop work as intended and are achieving the required levels of performance. Using this fit-for-purpose approach, the group defined three tiers of assays distinguished by their performance and extent of analytical characterization. Computational and statistical tools useful for the analysis of targeted MS results were described. Participants also detailed the information that authors need to provide in their manuscripts to enable reviewers and readers to clearly understand what procedures were performed and to evaluate the reliability of the peptide or protein quantification measurements reported. This paper presents a summary of the meeting and recommendations. C1 [Carr, Steven A.; Abbatiello, Susan E.; Mani, D. R.; Keshishian, Hasmik; Kuhn, Eric] Broad Inst MIT & Harvard, Cambridge, MA USA. [Ackermann, Bradley L.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Borchers, Christoph] Univ Victoria, Victoria, BC, Canada. [Domon, Bruno] Luxembourg Clin Prote Ctr, Luxembourg, Luxembourg. [Deutsch, Eric W.; Moritz, Robert] Inst Syst Biol, Seattle, WA USA. [Grant, Russell P.] Lab Corp Amer, Burlington, NC USA. [Hoofnagle, Andrew N.; MacLean, Brendan] Univ Washington, Seattle, WA 98195 USA. [Huettenhain, Ruth; Aebersold, Ruedi] Swiss Fed Inst Technol, Inst Mol Syst Biol, Zurich, Switzerland. [Huettenhain, Ruth; Bradshaw, Ralph A.; Burlingame, Alma L.; Oses-Prieto, Juan; Wiita, Arun] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Koomen, John M.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Liebler, Daniel C.] Vanderbilt Univ, Nashville, TN 37235 USA. [Liu, Tao] Pacific NW Natl Lab, Richland, WA 99352 USA. [Mansfield, Elizabeth; Boyne, Michael] US FDA, Silver Spring, MD USA. [Neubert, Hendrik] Pfizer, Andover, MA USA. [Paulovich, Amanda G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Reiter, Lukas] Biognosys Schlieren, Zurich, Switzerland. [Vitek, Olga] Purdue Univ, Purdue, IN USA. [Anderson, Leigh] SISCAPA Assay Technol Inc, Washington, DC USA. [Bethem, Robert] RAB Consulting, Novato, CA USA. [Blonder, Josip; Boja, Emily; Kinsinger, Christopher; Lee, Jerry S. H.; Rodriguez, Henry] NCI, NIH Bethesda, Bethesda, MD 20892 USA. [Botelho, Julianne] Ctr Dis Control & Prevent, Atlanta, GA USA. [Chan, Daniel; Lee, Jerry S. H.; Van Eyk, Jennifer] Johns Hopkins Univ, Baltimore, MD USA. [Lee, Sang-Won] Korea Univ, Seoul, South Korea. [Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Ritchie, James] Emory Univ, Atlanta, GA 30322 USA. [Srinivas, Pothur R.] NHLBI, NIH Bethesda, Bethesda, MD USA. [Townsend, R. Reid] Washington Univ, St Louis, MO USA. [Whiteley, Gordon] Liedos Biomed Res Inc, Frederick Natl Lab Canc Res, Washington, DC USA. [Weintraub, Susan] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Carr, SA (reprint author), Broad Inst MIT & Harvard, Dept Prote, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM scarr@broad.mit.edu RI Lee, Sang-Won/H-6760-2013; Lee, Jerry/K-4553-2014; OI Lee, Sang-Won/0000-0002-5042-0084; Oses-Prieto, Juan/0000-0003-4759-2341; Lee, Jerry/0000-0003-1515-0952; Liebler, Daniel/0000-0002-7873-3031 FU Broad Institute of MIT and Harvard; US National Institutes of Health from the National Cancer Institute Clinical Proteomics Tumor Analysis Consortium Initiative [U24CA160034]; US National Institutes of Health from the National Heart, Lung, and Blood Institute [HHSN268201000033C, R01HL096738] FX This work was supported in part by the Broad Institute of MIT and Harvard and by the following grants from the US National Institutes of Health: grant U24CA160034 from the National Cancer Institute Clinical Proteomics Tumor Analysis Consortium Initiative (to S.A.C.) and grants HHSN268201000033C and R01HL096738 from the National Heart, Lung, and Blood Institute (to S.A.C.). NR 98 TC 142 Z9 143 U1 11 U2 61 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAR PY 2014 VL 13 IS 3 BP 907 EP 917 DI 10.1074/mcp.M113.036095 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AC3BX UT WOS:000332391100017 PM 24443746 ER PT J AU Bosch-Marce, M Mohan, KV Gelderman, MP Ryan, PL Russek-Cohen, E Atreya, CD AF Bosch-Marce, Marta Mohan, Ketha V. K. Gelderman, Monique P. Ryan, Patricia L. Russek-Cohen, Estelle Atreya, Chintamani D. TI Preclinical safety evaluation of human platelets treated with antimicrobial peptides in severe combined immunodeficient mice SO TRANSFUSION LA English DT Article ID IN-VIVO RECOVERY; APHERESIS PLATELETS; MOUSE MODEL; BACTERIAL-CONTAMINATION; TRANSFUSION REACTIONS; FLOW-CYTOMETRY; RABBIT MODEL; EXPERIENCE; SURVIVAL; AGENTS AB BackgroundBacterial sepsis is a complication attributed to room temperature (RT)-stored platelets (PLTs) in transfusion medicine. Antimicrobial peptides (AMPs) are emerging as new therapeutic agents against microbes. We had previously demonstrated bactericidal activity of select synthetic AMPs against six types of bacteria in stored PLTs. In this report, we tested these AMPs for their potential antibody response and interference with the recovery and survival of human PLTs in an animal model. Study Design and MethodsTwo separate studies were conducted to evaluate the safety of the synthetic AMPs. 1) Two AMPs (PD3 and PD4), derived from thrombin-induced human PLT microbicidal protein, and four repeats of arginine-tryptophan (RW), containing two to five repeats (RW2-RW5), were tested in rabbits for potential antibody response. 2) RT-stored human PLTs treated for 2 hours with each of the six AMPs individually or with phosphate-buffered saline (PBS) alone were infused into severe combined immunodeficient (SCID) mice to evaluate their in vivo recovery and survival by flow cytometry. ResultsExcept for PD3, which showed a weak immune response, all other peptides did not induce any detectable antibodies in rabbits. Furthermore, all six AMPs tested did not significantly affect the in vivo recovery and survival of human PLTs in SCID mice compared to PBS alone-treated PLTs. ConclusionPreclinical evaluation studies reported here demonstrate that the selected AMPs used in the study did not adversely affect the human PLT recovery and survival in the SCID mouse model, suggesting further study of AMPs toward addressing the bacterial contamination of PLTs. C1 [Atreya, Chintamani D.] US FDA, Div Hematol, Sect Cell Biol, Lab Cellular Hematol, Bethesda, MD 20014 USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat, Bethesda, MD 20014 USA. RP Atreya, CD (reprint author), Bldg 29A,Room 2C-11,NIH Campus, Bethesda, MD 20892 USA. EM chintamani.atreya@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER); U.S. Department of Energy; U.S. Food and Drug Administration FX MBM and PLR are recipients of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intraagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. We thank J.G. Vostal for allowing us to use his animal protocol for these studies. NR 34 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAR PY 2014 VL 54 IS 3 BP 569 EP 576 DI 10.1111/trf.12318 PG 8 WC Hematology SC Hematology GA AC4MC UT WOS:000332494400013 PM 23808572 ER PT J AU Sager, PT Gintant, G Turner, JR Pettit, S Stockbridge, N AF Sager, Philip T. Gintant, Gary Turner, J. Rick Pettit, Syril Stockbridge, Norman TI Rechanneling the cardiac proarrhythmia safety paradigm: A meeting report from the Cardiac Safety Research Consortium SO AMERICAN HEART JOURNAL LA English DT Article ID CELL-DERIVED CARDIOMYOCYTES; DRUG DISCOVERY; DE-POINTES; HERG; ELECTROPHYSIOLOGY; PHARMACOLOGY; BLOCK; RISK; REPOLARIZATION; OPPORTUNITIES AB This white paper provides a summary of a scientific proposal presented at a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/Food and Drug Administration-sponsored Think Tank, held at Food and Drug Administration's White Oak facilities, Silver Spring, MD, on July 23, 2013, with the intention of moving toward consensus on defining a new paradigm in the field of cardiac safety in which proarrhythmic risk would be primarily assessed using nonclinical in vitro human models based on solid mechanistic considerations of torsades de pointes proarrhythmia. This new paradigm would shift the emphasis from the present approach that strongly relies on QTc prolongation (a surrogate marker of proarrhythmia) and could obviate the clinical Thorough QT study during later drug development. These discussions represent current thinking and suggestions for furthering our knowledge and understanding of the public health case for adopting a new, integrated nonclinical in vitro/in silico paradigm, the Comprehensive In Vitro Proarrhythmia Assay, for the assessment of a candidate drug's proarrhythmic liability, and for developing a public-private collaborative program to characterize the data content, quality, and approaches required to assess proarrhythmic risk in the absence of a Thorough QT study. This paper seeks to encourage multistakeholder input regarding this initiative and does not represent regulatory guidance. C1 [Sager, Philip T.] Stanford Univ, Palo Alto, CA 94304 USA. [Gintant, Gary] AbbVie, N Chicago, IL USA. [Turner, J. Rick] Quintiles, Durham, NC USA. [Pettit, Syril] HESI, Washington, DC USA. [Stockbridge, Norman] US FDA, Div Cardiovasc & Renal Drug Prod, White Oak, MD USA. RP Sager, PT (reprint author), Stanford Univ, 719 Carolina St, San Francisco, CA 94107 USA. EM psager@stanford.edu NR 31 TC 117 Z9 121 U1 3 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAR PY 2014 VL 167 IS 3 BP 292 EP 300 DI 10.1016/j.ahj.2013.11.004 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC3DT UT WOS:000332395900004 PM 24576511 ER PT J AU Calvo, G McMurray, JJV Granger, CB Alonso-Garcia, A Armstrong, P Flather, M Gomez-Outes, A Pocock, S Stockbridge, N Svensson, A Van de Werf, F AF Calvo, Gonzalo McMurray, John J. V. Granger, Christopher B. Alonso-Garcia, Angeles Armstrong, Paul Flather, Marcus Gomez-Outes, Antonio Pocock, Stuart Stockbridge, Norman Svensson, Anders Van de Werf, Frans TI Large streamlined trials in cardiovascular disease SO EUROPEAN HEART JOURNAL LA English DT Article ID CLINICAL-TRIALS C1 [Calvo, Gonzalo] Hosp Clin Barcelona, Inst Invest Agusti Pi & Sunyer IDIBAPS, Barcelona, Spain. [McMurray, John J. V.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Granger, Christopher B.] Duke Clin Res Inst, Durham, NC USA. [Alonso-Garcia, Angeles] Univ London, Cardiovasc Sci Res Ctr, London WC1E 7HU, England. [Armstrong, Paul] Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada. [Flather, Marcus] Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England. [Gomez-Outes, Antonio] Spanish Agcy Med & Med Devices AEMPS, Div Pharmacol & Clin Evaluat, Med Human Use, Madrid, Spain. [Pocock, Stuart] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. [Stockbridge, Norman] US FDA, Silver Spring, MD USA. [Svensson, Anders] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Van de Werf, Frans] Univ Leuven, Dept Cardiol, Louvain, Belgium. RP Calvo, G (reprint author), Hosp Clin Barcelona, Inst Invest Agusti Pi & Sunyer IDIBAPS, Barcelona, Spain. EM gcalvo@clinic.ub.es OI Van de Werf, Frans/0000-0001-9479-7767; mcmurray, john/0000-0002-6317-3975 NR 16 TC 5 Z9 6 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD MAR PY 2014 VL 35 IS 9 BP 544 EP 548 DI 10.1093/eurheartj/eht535 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC7TE UT WOS:000332734000006 PM 24385376 ER PT J AU Ali, MM Verrill, L Zhang, YT AF Ali, Mir M. Verrill, Linda Zhang, Yuanting TI Self-Reported Hand Washing Behaviors and Foodborne Illness: A Propensity Score Matching Approach SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FOOD SAFETY; CROSS-CONTAMINATION; RISK PERCEPTIONS; HYGIENE; COMMUNITY; HOME; OUTBREAKS; KITCHEN; WORKERS; SPREAD AB Hand washing is a simple and effective but easily overlooked way to reduce cross-contamination and the transmission of foodborne pathogens. In this study, we used the propensity score matching methodology to account for potential selection bias to explore our hypothesis that always washing hands before food preparation tasks is associated with a reduction in the probability of reported foodborne illness. Propensity score matching can simulate random assignment to a condition so that pretreatment observable differences between a treatment group and a control group are homogenous on all the covariates except the treatment variable. Using the U.S. Food and Drug Administration's 2010 Food Safety Survey, we estimated the effect of self-reported hand washing behavior on the probability of self-reported foodborne illness. Our results indicate that reported washing of hands with soap always before food preparation leads to a reduction in the probability of reported foodborne illness. C1 [Ali, Mir M.] Subst Abuse & Mental Hlth Serv Adm, Ctr Behav Hlth Stat & Qual, Rockville, MD 20857 USA. [Verrill, Linda; Zhang, Yuanting] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ali, MM (reprint author), Subst Abuse & Mental Hlth Serv Adm, Ctr Behav Hlth Stat & Qual, 1 Choke Cheny Rd, Rockville, MD 20857 USA. EM mir.ali@samhsa.hhs.gov NR 35 TC 6 Z9 6 U1 2 U2 8 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2014 VL 77 IS 3 BP 352 EP 358 DI 10.4315/0362-028X.JFP-13-286 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA AC5WK UT WOS:000332591500001 PM 24674424 ER PT J AU Skoog, SA Goering, PL Narayan, RJ AF Skoog, Shelby A. Goering, Peter L. Narayan, Roger J. TI Stereolithography in tissue engineering SO JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE LA English DT Article ID DESIGNED INTERNAL ARCHITECTURE; HYDROXYAPATITE IMPLANTS; LASER STEREOLITHOGRAPHY; MICRO-STEREOLITHOGRAPHY; SCAFFOLD FABRICATION; SIGNAL EXPRESSION; MICROSTEREOLITHOGRAPHY; CRANIOPLASTY; HYDROGELS; MICROFABRICATION AB Several recent research efforts have focused on use of computer-aided additive fabrication technologies, commonly referred to as additive manufacturing, rapid prototyping, solid freeform fabrication, or three-dimensional printing technologies, to create structures for tissue engineering. For example, scaffolds for tissue engineering may be processed using rapid prototyping technologies, which serve as matrices for cell ingrowth, vascularization, as well as transport of nutrients and waste. Stereolithography is a photopolymerization-based rapid prototyping technology that involves computer-driven and spatially controlled irradiation of liquid resin. This technology enables structures with precise microscale features to be prepared directly from a computer model. In this review, use of stereolithography for processing trimethylene carbonate, polycaprolactone, and poly(d,l-lactide) poly(propylene fumarate)-based materials is considered. In addition, incorporation of bioceramic fillers for fabrication of bioceramic scaffolds is reviewed. Use of stereolithography for processing of patient-specific implantable scaffolds is also discussed. In addition, use of photopolymerization-based rapid prototyping technology, known as two-photon polymerization, for production of tissue engineering scaffolds with smaller features than conventional stereolithography technology is considered. C1 [Skoog, Shelby A.; Goering, Peter L.] US FDA, Off Sci & Engn Labs, Div Biol, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Skoog, Shelby A.; Narayan, Roger J.] Univ North Carolina Chapel Hill, Joint Dept Biomed Engn, Raleigh, NC 27965 USA. [Skoog, Shelby A.; Narayan, Roger J.] N Carolina State Univ, Raleigh, NC 27965 USA. RP Narayan, RJ (reprint author), Univ North Carolina Chapel Hill, Joint Dept Biomed Engn, Raleigh, NC 27965 USA. EM roger_narayan@msn.com NR 59 TC 20 Z9 20 U1 9 U2 119 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-4530 EI 1573-4838 J9 J MATER SCI-MATER M JI J. Mater. Sci.-Mater. Med. PD MAR PY 2014 VL 25 IS 3 BP 845 EP 856 DI 10.1007/s10856-013-5107-y PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AC6WY UT WOS:000332667700023 PM 24306145 ER PT J AU Laurenson, JP Bloom, RA Page, S Sadrieh, N AF Laurenson, James P. Bloom, Raanan A. Page, Stephen Sadrieh, Nakissa TI Ethinyl Estradiol and Other Human Pharmaceutical Estrogens in the Aquatic Environment: A Review of Recent Risk Assessment Data SO AAPS JOURNAL LA English DT Review DE aquatic ecology; environmental impact; estrogens; regulatory science; toxicity ID ENDOCRINE-DISRUPTING CHEMICALS; MUNICIPAL WASTE-WATER; SURFACE WATERS; ORAL-CONTRACEPTIVES; DRINKING-WATER; 17-ALPHA-ETHINYL ESTRADIOL; SIGNIFICANT CONTRIBUTOR; ABIOTIC TRANSFORMATION; PERSONALIZED MEDICINE; MASS-SPECTROMETRY AB Interest in pharmaceuticals in the environment has increased substantially in recent years. Several studies in particular have assessed human and ecological risks from human pharmaceutical estrogens, such as 17 alpha-ethinyl estradiol (EE2). Regulatory action also has increased, with the USA and other countries developing rules to address estrogens and other pharmaceuticals in the environment. Accordingly, the Center for Drug Evaluation and Research at the US Food and Drug Administration has conducted a review and analysis of current data on the long-term ecological exposure and effects of EE2 and other estrogens. The results indicate that mean-flow long-term predicted environmental concentrations (PECs) of EE2 in approximately 99% or more of US surface water segments downstream of wastewater treatment plants are lower than a predicted no-effect concentration (PNEC) for aquatic chronic toxicity of 0.1 ng/L. Exceedances are expected to be primarily in localized, effluent-dominated water segments. The median mean-flow PEC is more than two orders of magnitude lower than this PNEC. Similar results exist for other pharmaceutical estrogens. Data also suggest that the contribution of EE2 more broadly to total estrogenic load in the environment from all sources (including other human pharmaceutical estrogens, endogenous estrogens, natural environmental estrogens, and industrial chemicals), while highly uncertain and variable, appears to be relatively low overall. Additional data and a more comprehensive approach for data collection and analysis for estrogenic substances in the environment, especially in effluent-dominated water segments in sensitive environments, would more fully characterize the risks. C1 [Laurenson, James P.; Bloom, Raanan A.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Page, Stephen] Amer Inst Res, Washington, DC 20007 USA. [Sadrieh, Nakissa] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Laurenson, JP (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM james.laurenson@fda.hhs.gov FU [HHSF223200910010I] FX The authors wish to thank Douglas Throckmorton, Deborah Livornese, Luis Valerio, and Roxane Modares from FDA/CDER for helpful discussions and review. The authors also wish to thank ICF International and IceTech, Inc. staff, in particular Margaret McVey, Arun Varghese, Isaac Warren, Christine Hartman, and Michael Smith, for providing much of the literature, data, and analysis used in this review (under contract no. HHSF223200910010I). Authors are listed according to first author (primary author) and last author (principal investigator) emphasis. NR 96 TC 17 Z9 17 U1 8 U2 103 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD MAR PY 2014 VL 16 IS 2 BP 299 EP 310 DI 10.1208/s12248-014-9561-3 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AC1AD UT WOS:000332225700013 PM 24470211 ER PT J AU Darpo, B Karnad, DR Badilini, F Florian, J Garnett, CE Kothari, S Panicker, GK Sarapa, N AF Darpo, Borje Karnad, Dilip R. Badilini, Fabio Florian, Jeff Garnett, Christine E. Kothari, Snehal Panicker, Gopi Krishna Sarapa, Nenad TI Are women more susceptible than men to drug-induced QT prolongation? Concentration-QT(c) modelling in a phase 1 study with oral rac-sotalol SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE gender; gender difference; PK/PD; QT prolongation; QT/QTc; rac-sotalol ID TORSADES-DE-POINTES; INTERVAL MEASUREMENT; MENSTRUAL-CYCLE; THOROUGH QT; SEX; GENDER; RISK; QUINIDINE; FIBRILLATION; D,L-SOTALOL AB AimTo study the differences in QT(c) interval on ECG in response to a single oral dose of rac-sotalol in men and women. MethodsContinuous 12-lead ECGs were recorded in 28 men and 11 women on a separate baseline day and following a single oral dose of 160mg rac-sotalol on the following day. ECGs were extracted at prespecified time points and upsampled to 1000Hz and analyzed manually in a central ECG laboratory on the superimposed median beat. Concentration-QTc analyses were performed using a linear mixed effects model. ResultsRac-sotalol produced a significant reduction in heart rate in men and in women. An individual correction method (QT(c)I) most effectively removed the heart rate dependency of the QT(c) interval. Mean QT(c)I was 10 to 15 ms longer in women at all time points on the baseline day. Rac-sotalol significantly prolonged QT(c)I in both genders. The largest mean change in QT(c)I (QT(c)I) was greater in females (68 ms (95% confidence interval (CI) 59, 76 ms) vs. 27 ms (95% CI 22, 32 ms) in males). Peak rac-sotalol plasma concentration was higher in women than in men (mean C-max 1.8gml(-1) (range 1.1-2.8) vs. 1.4gml(-1) (range 0.9-1.9), P = 0.0009). The slope of the concentration-QT(c)I relationship was steeper in women (30ms per gml(-1)vs. 23ms per gml(-1) in men; P = 0.0135). ConclusionsThe study provides evidence for a greater intrinsic sensitivity to rac-sotalol in women than in men for drug-induced delay in cardiac repolarization. C1 [Darpo, Borje] Karolinska Inst, Dept Clin Sci, Danderyds Hosp, Div Cardiovasc Med, SE-18257 Stockholm, Sweden. [Karnad, Dilip R.; Kothari, Snehal; Panicker, Gopi Krishna] Quintiles Cardiac Safety Serv, Bombay, Maharashtra, India. [Badilini, Fabio] AMPS LLC, New York, MD USA. [Florian, Jeff] US FDA, Div Pharmacometr, Silver Spring, MD USA. [Garnett, Christine E.] Certara, St Louis, MT USA. [Sarapa, Nenad] Hoffmann La Roche Inc, Clin Pharmacol, Nutley, NJ 07110 USA. RP Darpo, B (reprint author), Karolinska Inst, Dept Clin Sci, Danderyds Hosp, Div Cardiovasc Med, SE-18257 Stockholm, Sweden. EM borje.darpo@telia.com NR 36 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0306-5251 EI 1365-2125 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD MAR PY 2014 VL 77 IS 3 BP 522 EP 531 DI 10.1111/bcp.12201 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB2GZ UT WOS:000331612500013 PM 23819796 ER PT J AU Ke, AB Nallani, SC Zhao, P Rostami-Hodjegan, A Unadkat, JD AF Ke, Alice Ban Nallani, Srikanth C. Zhao, Ping Rostami-Hodjegan, Amin Unadkat, Jashvant D. TI Expansion of a PBPK model to predict disposition in pregnant women of drugs cleared via multiple CYP enzymes, including CYP2B6, CYP2C9 and CYP2C19 SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE CYP2B6; CYP2C19; CYP2C9; PBPK; pharmacokinetics; pregnancy ID HUMAN METHADONE METABOLISM; HEALTHY-VOLUNTEERS; IN-VITRO; INTERINDIVIDUAL VARIABILITY; PHARMACOKINETIC INTERACTION; TRANSPORTER INHIBITION; PLASMA-CONCENTRATIONS; ACTIVE METABOLITES; STEADY-STATE; GLYBURIDE AB AimConducting PK studies in pregnant women is challenging. Therefore, we asked if a physiologically-based pharmacokinetic (PBPK) model could be used to predict the disposition in pregnant women of drugs cleared by multiple CYP enzymes. MethodsWe expanded and verified our previously published pregnancy PBPK model by incorporating hepatic CYP2B6 induction (based on in vitro data), CYP2C9 induction (based on phenytoin PK) and CYP2C19 suppression (based on proguanil PK), into the model. This model accounted for gestational age-dependent changes in maternal physiology and hepatic CYP3A, CYP1A2 and CYP2D6 activity. For verification, the pregnancy-related changes in the disposition of methadone (cleared by CYP2B6, 3A and 2C19) and glyburide (cleared by CYP3A, 2C9 and 2C19) were predicted. ResultsPredicted mean post-partum to second trimester (PP:T-2) ratios of methadone AUC, C-max and C-min were 1.9, 1.7 and 2.0, vs. observed values 2.0, 2.0 and 2.6, respectively. Predicted mean post-partum to third trimester (PP:T-3) ratios of methadone AUC, C-max and C-min were 2.1, 2.0 and 2.4, vs. observed values 1.7, 1.7 and 1.8, respectively. Predicted PP:T-3 ratios of glyburide AUC, C-max and C-min were 2.6, 2.2 and 7.0 vs. observed values 2.1, 2.2 and 3.2, respectively. ConclusionsOur PBPK model integrating prior physiological knowledge, in vitro and in vivo data, allowed successful prediction of methadone and glyburide disposition during pregnancy. We propose this expanded PBPK model can be used to evaluate different dosing scenarios, during pregnancy, of drugs cleared by single or multiple CYP enzymes. C1 [Ke, Alice Ban; Unadkat, Jashvant D.] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Ke, Alice Ban; Nallani, Srikanth C.; Zhao, Ping] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Rostami-Hodjegan, Amin] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester, Lancs, England. [Rostami-Hodjegan, Amin] Simcyp Ltd, Sheffield, S Yorkshire, England. RP Unadkat, JD (reprint author), Univ Washington, Dept Pharmaceut, Box 357610, Seattle, WA 98195 USA. EM jash@u.washington.edu FU Office of Women's Health, US Food and Drug Administration FX All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare ABK was supported by the Office of Women's Health, US Food and Drug Administration, JDU was a member of the Simcyp (now part of Certara) scientific advisory board and no other relationships or activities that could appear to have influenced the submitted work. NR 68 TC 14 Z9 14 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0306-5251 EI 1365-2125 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD MAR PY 2014 VL 77 IS 3 BP 554 EP 570 DI 10.1111/bcp.12207 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB2GZ UT WOS:000331612500016 PM 23834474 ER PT J AU Dhakal, S Burwen, DR Polakowski, LL Zinderman, CE Wise, RP AF Dhakal, Sanjaya Burwen, Dale R. Polakowski, Laura L. Zinderman, Craig E. Wise, Robert P. TI Assessment of tissue allograft safety monitoring with administrative healthcare databases: a pilot project using Medicare data SO CELL AND TISSUE BANKING LA English DT Article DE Tissue safety; Allografts; Post-transplant infection; Administrative data ID TRACEABILITY; ORGAN; XENOTRANSPLANTATION; TRANSPLANTATION; TRANSMISSION; INFECTIONS; CELLS; RISK AB Assess whether Medicare data are useful for monitoring tissue allograft safety and utilization. We used health care claims (billing) data from 2007 for 35 million fee-for-service Medicare beneficiaries, a predominantly elderly population. Using search terms for transplant-related procedures, we generated lists of ICD-9-CM and CPTA (R) codes and assessed the frequency of selected allograft procedures. Step 1 used inpatient data and ICD-9-CM procedure codes. Step 2 added non-institutional provider (e.g., physician) claims, outpatient institutional claims, and CPT codes. We assembled preliminary lists of diagnosis codes for infections after selected allograft procedures. Many ICD-9-CM codes were ambiguous as to whether the procedure involved an allograft. Among 1.3 million persons with a procedure ascertained using the list of ICD-9-CM codes, only 1,886 claims clearly involved an allograft. CPT codes enabled better ascertainment of some allograft procedures (over 17,000 persons had corneal transplants and over 2,700 had allograft skin transplants). For spinal fusion procedures, CPT codes improved specificity for allografts; of nearly 100,000 patients with ICD-9-CM codes for spinal fusions, more than 34,000 had CPT codes indicating allograft use. Monitoring infrequent events (infections) after infrequent exposures (tissue allografts) requires large study populations. A strength of the large Medicare databases is the substantial number of certain allograft procedures. Limitations include lack of clinical detail and donor information. Medicare data can potentially augment passive reporting systems and may be useful for monitoring tissue allograft safety and utilization where codes clearly identify allograft use and coding algorithms can effectively screen for infections. C1 [Dhakal, Sanjaya; Burwen, Dale R.; Polakowski, Laura L.; Zinderman, Craig E.; Wise, Robert P.] US FDA, DE, OBE, CBER, Rockville, MD 20852 USA. RP Zinderman, CE (reprint author), US FDA, DE, OBE, CBER, 1401 Rockville Pike WOC I 441 S, Rockville, MD 20852 USA. EM craig.zinderman@fda.hhs.gov NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9333 EI 1573-6814 J9 CELL TISSUE BANK JI Cell Tissue Banking PD MAR PY 2014 VL 15 IS 1 BP 75 EP 84 DI 10.1007/s10561-013-9376-y PG 10 WC Cell Biology; Engineering, Biomedical SC Cell Biology; Engineering GA AC2GV UT WOS:000332318700010 PM 23824508 ER PT J AU Johannesen, L Garnett, C Malik, M AF Johannesen, Lars Garnett, Christine Malik, Marek TI Impact of Electrocardiographic Data Quality on Moxifloxacin Response in Thorough QT/QTc Studies SO DRUG SAFETY LA English DT Article ID QT-INTERVAL; PRECISION AB Thorough QT studies are typically conducted for drugs with systemic bioavailability and include a positive control, typically moxifloxacin, with a well-described QTc effect. This study tested two hypotheses: that (i) re-measuring the QT intervals based on electrocardiogram (ECG) pattern similarity improves the moxifloxacin time profile, and (ii) that study conduct influences the ability to detect a typical moxifloxacin time profile. ECGs from 65 studies with available moxifloxacin plasma concentrations were obtained, including four studies with an unexpected moxifloxacin response. Residual error of a concentration-QT model was evaluated before and after re-measuring the QT interval based on ECG pattern similarity. Intra-replicate heart rate differences were calculated using the original heart rate measurements and the 10-s average heart rates. Similarity re-measurements reduced the residual error of the model (before vs. after of 8.43 +/- A 2.00 vs. 7.55 +/- A 1.86 ms; p < 0.001). For both original and averaged 10-s heart rate, intra-replicate heart rate differences were significantly lower (p < 0.001) in studies with the expected response than in those with an unexpected time profile. The pattern similarity measurement methodology reduces the residual error of the model, which influences the time profile of the moxifloxacin response. Accuracy of study conduct, represented by intra-replicate heart rate differences, separated studies with and without the expected moxifloxacin time profile. C1 [Johannesen, Lars; Garnett, Christine] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Off Translat Sci,Div Pharmacometr, Silver Spring, MD USA. [Johannesen, Lars] Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden. [Johannesen, Lars] Karolinska Univ Hosp, Stockholm, Sweden. [Johannesen, Lars] FDA, Silver Spring, MD 20993 USA. [Garnett, Christine] Certara, Cary, NC USA. [Malik, Marek] Univ London, St Pauls Cardiac Elect, London, England. RP Johannesen, L (reprint author), FDA, 10903 New Hampshire Ave Bldg 62,RM 2127E, Silver Spring, MD 20993 USA. EM lars.johannesen@fda.hhs.gov FU Center for Drug Evaluation and Research FX The authors are grateful to Dr. Norman Stockbridge of the US Food and Drug Administration for his substantial guidance on the topic and his help with preparing the manuscript. This project was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. NR 15 TC 6 Z9 6 U1 0 U2 0 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PD MAR PY 2014 VL 37 IS 3 BP 183 EP 189 DI 10.1007/s40264-014-0142-2 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA AC2HN UT WOS:000332320600006 PM 24554350 ER PT J AU Johannesen, L Garnett, C Malik, M AF Johannesen, Lars Garnett, Christine Malik, Marek TI Electrocardiographic Data Quality in Thorough QT/QTc Studies SO DRUG SAFETY LA English DT Article ID QT; PRECISION AB Most drugs with systemic bioavailability have to undergo a thorough QT (TQT) study, which includes a pharmacologic positive control. A set of QTc-quality tests was recently proposed with the possible aim of removing the need for a positive control. We evaluated the influence of QT measurement and QTc computation methodology on the proposed QTc-quality tests. The baseline ECG waveforms and fiducial points were retrieved from 34 crossover TQT studies that had full-day baseline ECGs prior to each study period. The QT measurement methodology and recorder type were retrieved from study reports. The influence of QTc computation methodology was investigated by applying the pattern-matching technique and/or using the 10-s average heart rate. There were no statistical differences in any QTc-quality test values between studies using continuous or 10-s bedside recordings and, in a subset of the quality test, an increase of data quality for semi-automatically read studies compared with those manually read (p < 0.01). There was a significant improvement (p < 0.01) in all the QTc-quality test values for QTc measurements obtained by using pattern matching with or without 10-s average heart rate in comparison to the original QTc measurements. The findings suggest that QTc quality is mostly driven by the QTc measurement methodology rather than other study-related factors. C1 [Johannesen, Lars; Garnett, Christine] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol,Off Translat Sci, Div Pharmacometr, Silver Spring, MD 20993 USA. [Johannesen, Lars] Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden. [Johannesen, Lars] Karolinska Univ Hosp, Stockholm, Sweden. [Johannesen, Lars] US FDA, Silver Spring, MD 20993 USA. [Garnett, Christine] Certara, Cary, NC USA. [Malik, Marek] Univ London, St Pauls Cardiac Elect, London, England. [Malik, Marek] Univ London Imperial Coll Sci Technol & Med, London, England. RP Johannesen, L (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 62,RM 2127E, Silver Spring, MD 20993 USA. EM lars.johannesen@fda.hhs.gov FU Center for Drug Evaluation and Research FX The authors are grateful to Dr. Norman Stockbridge of the FDA for his substantial guidance on the topic and his help with preparing this manuscript. This project was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA. NR 10 TC 8 Z9 8 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 EI 1179-1942 J9 DRUG SAFETY JI Drug Saf. PD MAR PY 2014 VL 37 IS 3 BP 191 EP 197 DI 10.1007/s40264-014-0140-4 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA AC2HN UT WOS:000332320600007 PM 24554349 ER PT J AU Wen, Z Nichols, JD Pollock, KH Waser, PM AF Wen, Zhi Nichols, James D. Pollock, Kenneth H. Waser, Peter M. TI A robust design capture-recapture model with multiple age classes augmented with population assignment data SO ENVIRONMENTAL AND ECOLOGICAL STATISTICS LA English DT Article DE Capture-recapture; Genetic assignment procedures; Kangaroo rat; Robust design; Single site; Superpopulation; Two age groups ID INTERPOPULATION DISPERSAL; TEMPORARY EMIGRATION; KANGAROO RATS; IMMIGRATION; SURVIVAL AB The relative contribution of in situ reproduction versus immigration to the recruitment process is important to ecologists. Here we consider a robust design superpopulation capture-recapture model for a population with two age classes augmented with population assignment data. We first use age information to estimate the entry probabilities of new animals originating via in situ reproduction and immigration separately for all except the first period. Then we combine age and population assignment information with the capture-recapture model, which enables us to estimate the entry probability of in situ births and the entry probability of immigrants separately for all sampling periods. Further, this augmentation of age specific capture-recapture data with population assignment data greatly improves the estimators' precision. We apply our new model to a capture-recapture data set with genetic information for banner-tailed kangaroo rats in Southern Arizona. We find that many more individuals are born in situ than are immigrants for all time periods. Young animals have lower survival probabilities than adults born in situ. Adult animals born in situ have higher survival probabilities than adults that were immigrants. C1 [Wen, Zhi] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Nichols, James D.] USGS, Patuxent Wildlife Res Ctr, Laurel, MD USA. [Pollock, Kenneth H.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. [Waser, Peter M.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. RP Wen, Z (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM zhiwenislucky@gmail.com FU NSF [DEB 0816925] FX We thank the NSF, for support (DEB 0816925). NR 32 TC 0 Z9 0 U1 1 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1352-8505 EI 1573-3009 J9 ENVIRON ECOL STAT JI Environ. Ecol. Stat. PD MAR PY 2014 VL 21 IS 1 BP 41 EP 59 DI 10.1007/s10651-013-0243-6 PG 19 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA AB9OU UT WOS:000332125300003 ER PT J AU Sulaiman, IM Ortega, Y Simpson, S Kerdahi, K AF Sulaiman, Irshad M. Ortega, Ynes Simpson, Steven Kerdahi, Khalil TI Genetic characterization of human-pathogenic Cyclospora cayetanensis parasites from three endemic regions at the 18S ribosomal RNA locus SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Gastro intestinal parasite; Foodborne disease; Genetic marker; Nucleotide sequencing; Rapid detection ID CYANOBACTERIUM-LIKE BODIES; PROTEIN HSP70 GENE; MOLECULAR CHARACTERIZATION; CRYPTOSPORIDIUM PARASITES; ENTEROCYTOZOON-BIENEUSI; PHYLOGENETIC ANALYSIS; BABESIA-GIBSONI; SP APICOMPLEXA; HEAT-SHOCK-PROTEIN-70; INFECTION AB Cyclospora cayetanensis is an apicocomplexan parasite that infects the gastrointestinal tract and causes acute diarrheal disease in humans. In recent years, this human-pathogenic parasite has led to several foodborne outbreaks in the United States and Canada, mostly associated with imported produce. Understanding the biology and epidemiology of C. cayetanensis is difficult because little is known about its origin, possible zoonotic reservoirs, and genetic relationships with other coccidian parasites. Recently, we developed a 70 kDa heat shock protein (HSP70) gene based nested PCR protocol for detection of C. cayetanensis parasite and sequenced the PCR products of 16 human isolates from Nepal, Mexico, and Peru. In this study, we have characterized the regions of 18S ribosomal RNA (rRNA) gene of 17 human C. cayetanensis isolates for molecular detection, and also to ascertain the genetic diversity of this parasite. The 18S rRNA primer sets were further tested by PCR amplification followed by nucleotide sequencing of the PCR amplified products of previously characterized C. cayetanensis isolates from three endemic regions at HSP70 locus. Although no genetic polymorphism was observed at the regions of HSP70 locus characterized in our previous study, the data analysis of this study revealed a minor genetic diversity at the 18S rRNA locus among the C. cayetanensis isolates. The 18S rRNA gene-based nested PCR protocol provides a useful genetic marker for the detection of C. cayetanensis parasite and confirms it as a genetically distinct species in genus Cyclospora. The results also supported lack of geographic segregation and existence of genetically homogeneous population for the C. cayetanensis parasites both at the HSP70 as well as at the18S rRNA loci. Published by Elsevier B.V. C1 [Sulaiman, Irshad M.; Simpson, Steven; Kerdahi, Khalil] US FDA, Southeast Reg Lab, Atlanta, GA 30309 USA. [Ortega, Ynes] Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. RP Sulaiman, IM (reprint author), US FDA, Mol Genet Lab, Microbiol Sci Branch, 60 Eighth St NE, Atlanta, GA 30309 USA. EM irshad.sulaiman@fda.hhs.gov FU Division of Field Sciences of FDA FX The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the views or official position of the U.S. Food and Drug Administration (FDA). The names of vendors or manufacturers are provided as examples of available product sources; inclusion does not imply endorsement of the vendors, manufacturers, or products by the FDA or the U.S. Department of Health and Human Services. This study was supported in part by funding from the Division of Field Sciences of FDA. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Thanks are also due to Nicky Sulaiman for her invaluable help in completion of this study and comments on this manuscript. NR 33 TC 6 Z9 6 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD MAR PY 2014 VL 22 BP 229 EP 234 DI 10.1016/j.meegid.2013.07.015 PG 6 WC Infectious Diseases SC Infectious Diseases GA AC1SK UT WOS:000332276300028 PM 23891667 ER PT J AU Arya, V Florian, J Marcus, KA Reynolds, KS Lewis, LL Sherwat, AI AF Arya, Vikram Florian, Jeffry Marcus, Kendall A. Reynolds, Kellie S. Lewis, Linda L. Sherwat, Adam I. TI Does an Increase in Serum Creatinine always Reflect Renal Injury? The Case of Stribild (R) SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Stribild (R); renal tubulopathy; MATE 1 transporters; creatinine clearance ID CO-FORMULATED ELVITEGRAVIR; INITIAL TREATMENT; HIV-1 INFECTION; DOUBLE-BLIND; TENOFOVIR; COBICISTAT; NEPHROTOXICITY; EMTRICITABINE; PHASE-3; DISEASE C1 [Arya, Vikram; Reynolds, Kellie S.] US FDA, Div Clin Pharmacol 4, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Florian, Jeffry] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Marcus, Kendall A.; Lewis, Linda L.; Sherwat, Adam I.] US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Arya, V (reprint author), 10903 New Hampshire Ave,Bldg 51,Room 2144, Silver Spring, MD 20993 USA. EM vikram.arya@fda.hhs.gov NR 17 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4604 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAR PY 2014 VL 54 IS 3 BP 279 EP 281 DI 10.1002/jcph.223 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AA7EM UT WOS:000331260100006 ER PT J AU Rahman, Z Xu, XM Katragadda, U Krishnaiah, YSR Yu, L Khan, MA AF Rahman, Ziyaur Xu, Xiaoming Katragadda, Usha Krishnaiah, Yellela S. R. Yu, Lawrence Khan, Mansoor A. TI Quality by Design Approach for Understanding the Critical Quality Attributes of Cyclosporine Ophthalmic Emulsion SO MOLECULAR PHARMACEUTICS LA English DT Article DE quality by design; cyclosporine; microemulsion; ophthalmic; critical quality attributes droplet size; zeta potential; viscosity; diffusion ID DRY EYE DISEASE; OCULAR DISTRIBUTION; PLGA NANOPARTICLES; PARTICLE-SIZE; TEMPERATURE; STABILITY; PENETRATION; MICELLES; EFFICACY; CARRIERS AB Restasis is an ophthalmic cyclosporine emulsion used for the treatment of dry eye syndrome. There are no generic products for this product, probably because of the limitations on establishing in vivo bioequivalence methods and lack of alternative in vitro bioequivalence testing methods. The present investigation was carried out to understand and identify the appropriate in vitro methods that. can discriminate the effect of formulation and process variables on critical quality attributes (CQA) of cyclosporine microemulsion formulations having the same qualitative (Q1) and quantitative (Q2) composition as that of Restasis. Quality by design (QbD) approach was used to understand the effect of formulation and process variables on critical quality attributes (CQA) of cyclosporine microemulsion. The formulation variables chosen were mixing order method, phase volume ratio, and pH adjustment method, while the process variables were temperature of primary and raw emulsion formation, microfluidizer pressure, and number of pressure cycles. The responses selected were particle size, turbidity, zeta potential, viscosity, osmolality, surface tension, contact angle, pH, and drug diffusion. The selected independent variables showed statistically significant (p < 0.05) effect on droplet size, zeta potential, viscosity, turbidity, and osmolality. However, the surface tension, contact angle, pH, and drug diffusion were not significantly affected by independent variables. In summary, in vitro methods can detect formulation and manufacturing changes and would thus be important for quality control or sameness of cyclosporine ophthalmic products. C1 [Rahman, Ziyaur; Xu, Xiaoming; Katragadda, Usha; Krishnaiah, Yellela S. R.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Yu, Lawrence] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov OI Xu, Xiaoming/0000-0003-1672-0830; Rahman, Ziyaur/0000-0002-0402-825X NR 39 TC 5 Z9 5 U1 3 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD MAR PY 2014 VL 11 IS 3 BP 787 EP 799 DI 10.1021/mp400484g PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AC2QI UT WOS:000332348600013 PM 24423028 ER PT J AU Gewandter, JS Smith, SM McKeown, A Burke, LB Hertz, SH Hunsinger, M Katz, NP Lin, AH McDermott, MP Rappaport, BA Williams, MR Turk, DC Dworkin, RH AF Gewandter, Jennifer S. Smith, Shannon M. McKeown, Andrew Burke, Laurie B. Hertz, Sharon H. Hunsinger, Matthew Katz, Nathaniel P. Lin, Allison H. McDermott, Michael P. Rappaport, Bob A. Williams, Mark R. Turk, Dennis C. Dworkin, Robert H. TI Reporting of primary analyses and multiplicity adjustment in recent analgesic clinical trials: ACTTION systematic review and recommendations SO PAIN LA English DT Review DE Primary analysis reporting; Multiplicity; Systematic review ID END-POINT; IMMPACT RECOMMENDATIONS; CHRONIC PAIN; OUTCOMES; DESIGN; TESTS AB Performing multiple analyses in clinical trials can inflate the probability of a type I error, or the chance of falsely concluding a significant effect of the treatment. Strategies to minimize type I error probability include prespecification of primary analyses and statistical adjustment for multiple comparisons, when applicable. The objective of this study was to assess the quality of primary analysis reporting and frequency of multiplicity adjustment in 3 major pain journals (ie, European Journal of Pain, Journal of Pain, and PAIN (R)). A total of 161 randomized controlled trials investigating noninvasive pharmacological treatments or interventional treatments for pain, published between 2006 and 2012, were included. Only 52% of trials identified a primary analysis, and only 10% of trials reported prespecification of that analysis. Among the 33 articles that identified a primary analysis with multiple testing, 15 (45%) adjusted for multiplicity; of those 15, only 2 (13%) reported prespecification of the adjustment methodology. Trials in clinical pain conditions and industry-sponsored trials identified a primary analysis more often than trials in experimental pain models and non-industry-sponsored trials, respectively. The results of this systematic review demonstrate deficiencies in the reporting and possibly the execution of primary analyses in published analgesic trials. These deficiencies can be rectified by changes in, or better enforcement of, journal policies pertaining to requirements for the reporting of analyses of clinical trial data. (C) 2013 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Gewandter, Jennifer S.; Smith, Shannon M.; McKeown, Andrew; Williams, Mark R.; Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. [Burke, Laurie B.; Hertz, Sharon H.; Lin, Allison H.; Rappaport, Bob A.] US FDA, Silver Spring, MD USA. [Hunsinger, Matthew] Univ Pacific, Sch Profess Psychol, Hillsboro, OR USA. [Katz, Nathaniel P.] Analges Solut, Natick, MA USA. [Katz, Nathaniel P.] Tufts Univ, Boston, MA 02111 USA. [McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Gewandter, JS (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, 601 Elmwood Ave,Box 604, Rochester, NY 14642 USA. EM jennifer_gewandter@urmc.rochester.edu FU Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership; ACTTION public-private partnership; FDA FX The views expressed in this article are those of the authors, and no official endorsement by the Food and Drug Administration (FDA) or the pharmaceutical companies that provided unrestricted grants to support the activities of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership should be inferred. Financial support for this project was provided by the ACTTION public-private partnership, which has received research contracts, grants, or other revenue from the FDA, Astellas, BristolMyers Squibb, Collegium, Depomed, Eli Lilly, Horizon, Jazz, Johnson & Johnson, Mallinckrodt, Pfizer, Purdue, Zalicus, and other sources. NR 28 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD MAR PY 2014 VL 155 IS 3 BP 461 EP 466 DI 10.1016/j.pain.2013.11.009 PG 6 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA AB4KG UT WOS:000331757800004 PM 24275257 ER PT J AU Volpe, DA Tobin, GA Tavakkoli, F Dowling, TC Light, PD Parker, RJ AF Volpe, Donna A. Tobin, Grainne A. Tavakkoli, Fatemeh Dowling, Thomas C. Light, Paul D. Parker, Robert J. TI Effect of uremic serum and uremic toxins on drug metabolism in human microsomes SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Chronic renal failure; Metabolism; Uremic serum; Uremic toxins ID CHRONIC-RENAL-FAILURE; HUMAN LIVER-MICROSOMES; HEPATIC CYTOCHROME-P450; DOWN-REGULATION; IN-VITRO; ALPHA-GLOBULINS; GAMMA-GLOBULINS; KIDNEY-DISEASE; HEMODIALYSIS; TRANSPORT AB There is increasing evidence that renal impairment modifies nonrenal drug clearance through drug metabolizing cytochrome P450 (CYP) enzymes. In this study, the direct inhibitory effect of serum from chronic renal failure (CRF) patients receiving dialysis was evaluated in CYP3A4 (testosterone) and CYP2B6 (bupropion) metabolism assays. Human liver microsomes were incubated with ultrafiltered serum collected pre- and post-hemodialysis from ten CRF patients. Additionally, several uremic toxins were evaluated in the CYP3A4 assay. In only three patients was there a significant decrease or increase in testosterone or bupropion metabolism post-dialysis. Urea, mannitol, guanidine, homocysteine, uridine and creatinine had no effect on CYP3A4 metabolism. CMPF, hippuric acid and p-cresol had IC50 values that fell within CRF patient plasma concentrations. The IC50 values for indoxyl sulfate and indole-3-acetic acid were greater than CRF plasma concentrations. The lack of a consistent effect on CYP3A4 or CYP2B6 metabolism by uremic serum may be due in part to the frequency of hemodialysis in these patients which reduced the accumulation of uremic toxins. CMPF, hippuric acid and p-cresol have the ability to inhibit CYP3A4 metabolism at clinical concentrations which may correspond to reports of changes in hepatic metabolism in some CRF patients. Published by Elsevier Inc. C1 [Volpe, Donna A.; Tobin, Grainne A.; Parker, Robert J.] US FDA, Div Drug Safety Res, Silver Spring, MD 20993 USA. [Tavakkoli, Fatemeh; Dowling, Thomas C.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Light, Paul D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Volpe, DA (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM donna.volpe@fda.hhs.gov RI Dowling, Thomas/D-2147-2013 OI Dowling, Thomas/0000-0003-3214-9283 NR 37 TC 7 Z9 10 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 EI 1096-0295 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD MAR PY 2014 VL 68 IS 2 BP 297 EP 303 DI 10.1016/j.yrtph.2013.10.006 PG 7 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA AB9QQ UT WOS:000332131100011 PM 24184159 ER PT J AU Pearsall, BM Araojo, R Hinton, D AF Pearsall, Bryon M. Araojo, Richardae Hinton, Denise TI Essential Medication Information for Patients Ensuring Access SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE pharmaceutical preparations; consumer information handout; consumer information; patient education handout; drug information services; drug labeling AB The US Food and Drug Administration (FDA) is developing a new framework to provide patients with quality, up-to-date prescription product information that will promote the safe use of prescribed medication. The goal of this new Patient Medication Information is to provide patient-oriented information for each prescription product. Described in this article are the efforts of the FDA to help ensure that patients receive essential prescription medication information. C1 [Pearsall, Bryon M.; Araojo, Richardae; Hinton, Denise] US FDA, Ctr Drug Evaluat & Res, Off Med Policy Initiat, Silver Spring, MD 20993 USA. RP Pearsall, BM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Med Policy Initiat, WO51 RM6352,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Bryon.Pearsall@fda.hhs.gov NR 11 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 EI 2168-4804 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD MAR PY 2014 VL 48 IS 2 BP 162 EP 164 DI 10.1177/2168479013507437 PG 3 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA AB9IY UT WOS:000332107200006 ER PT J AU Archdeacon, P Grandinetti, C Vega, JM Balderson, D Kramer, JM AF Archdeacon, Patrick Grandinetti, Cheryl Vega, Jose M. Balderson, David Kramer, Judith M. TI Optimizing Expedited Safety Reporting for Drugs and Biologics Subject to an Investigational New Drug Application SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE safety; reporting; clinical trials AB In September 2010, the US Food and Drug Administration (FDA) published a final rule governing the requirements for expedited safety reporting for products subject to an investigational new drug application. The rule clarified the types of safety information that qualify for expedited reporting. Its intent was to improve the overall quality of safety reporting by reducing the number of uninterpretable individual reports sent to the FDA and clinical investigators. In December 2011, we surveyed pharmaceutical and biotechnology sponsors regarding their safety reporting practices. We convened a group of experts and a biostatistics work group to review the survey results and identify gaps between current practice and the final safety reporting rule. Most sponsors had not changed their approach to expedited reporting of serious adverse events. We devised recommendations to help sponsors optimize their premarket safety systems to reduce the number of uninformative expedited reports and ensure recognition of important safety issues for an investigational drug as early as possible in development. C1 [Archdeacon, Patrick; Grandinetti, Cheryl] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Vega, Jose M.; Balderson, David] Amgen Inc, Thousand Oaks, CA 91320 USA. [Kramer, Judith M.] Duke Univ, Sch Med, Duke Clin Res Inst, Duke Translat Med Inst, Durham, NC 27715 USA. [Kramer, Judith M.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. RP Kramer, JM (reprint author), Duke Univ, Sch Med, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM judith.kramer@duke.edu FU US Food and Drug Administration [U19FD003800] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was conducted by in-kind contribution of effort by authors and organizations working with the Clinical Trials Transformation Initiative (CTTI; www.ctti-clinicaltrials.org), as well as staff effort and meetings supported by CTTI funding (derived both from pooled fees from member organizations and from a cooperative agreement, U19FD003800, awarded to Duke University by the US Food and Drug Administration). NR 9 TC 2 Z9 2 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 EI 2168-4804 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD MAR PY 2014 VL 48 IS 2 BP 200 EP 207 DI 10.1177/2168479013509382 PG 8 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA AB9IY UT WOS:000332107200011 ER PT J AU Zhang, JJ Chen, HY He, K Tang, SH Justice, R Keegan, P Pazdur, R Sridhara, R AF Zhang, Jenny J. Chen, Huanyu He, Kun Tang, Shenghui Justice, Robert Keegan, Patricia Pazdur, Richard Sridhara, Rajeshwari TI Reply to Letter to the Editor: Local Evaluation and Blinded Central Review Comparison a Victim of Meta-analysis Shortcomings SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Letter ID ONCOLOGY CLINICAL-TRIALS; TUMOR PROGRESSION C1 [Zhang, Jenny J.] Gilead Sci, Foster City, CA USA. [Chen, Huanyu; He, Kun; Tang, Shenghui; Sridhara, Rajeshwari] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Div Biometr V,Off Biostat, Silver Spring, MD 20993 USA. [Justice, Robert; Keegan, Patricia; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Hematol & Oncol Prod, Silver Spring, MD USA. RP Sridhara, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Div Biometr V,Off Biostat, Silver Spring, MD 20993 USA. EM rajeshwari.sridhara@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 EI 2168-4804 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD MAR PY 2014 VL 48 IS 2 BP NP1 EP NP2 DI 10.1177/2168479014520698 PG 2 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA AB9IY UT WOS:000332107200001 ER PT J AU Maynard, JW McAdams-DeMarco, MA Law, A Kao, LD Gelber, AC Coresh, J Baer, AN AF Maynard, Janet W. McAdams-DeMarco, Mara A. Law, Andrew Kao, Linda Gelber, Allan C. Coresh, Josef Baer, Alan N. TI Racial Differences in Gout Incidence in a Population-Based Cohort: Atherosclerosis Risk in Communities Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE gout; inflammatory arthritis; race; uric acid ID ADMINISTRATIVE CLAIMS ANALYSIS; FOOD FREQUENCY QUESTIONNAIRE; GLOMERULAR-FILTRATION-RATE; SERUM URATE LEVELS; URIC-ACID; UNITED-STATES; KIDNEY-FUNCTION; GENETIC-LOCI; FOLLOW-UP; MEN AB We examined racial differences in gout incidence among black and white participants in a longitudinal, population-based cohort and tested whether racial differences were explained by higher levels of serum urate. The Atherosclerosis Risk in Communities Study is a prospective, US population-based cohort study of middle-aged adults enrolled between 1987 and 1989 with ongoing annual follow-up through 2012. We estimated the adjusted hazard ratios and 95% confidence intervals of incident gout by race among 11,963 men and women using adjusted Cox proportional hazards models. The cohort was 23.6% black. The incidence rate of gout was 8.4 per 10,000 person-years (15.5/10,000 person-years for black men, 12.0/10,000 person-years for black women, 9.4/10,000 person-years for white men, and 5.0/10,000 person-years for white women; P < 0.001). Black participants had an increased risk of incident gout (for women, adjusted hazard ratio (HR) = 1.69, 95% confidence interval (CI): 1.29, 2.22; for men, adjusted HR = 1.92, 95% CI: 1.44, 2.56). Upon further adjustment for uric acid levels, there was modest attenuation of the association of race with incident gout (for women, adjusted HR = 1.62, 95% CI: 1.24, 2.22; for men, adjusted HR = 1.49, 95% CI: 1.11, 2.00) compared with white participants. In this US population-based cohort, black women and black men were at increased risk of developing gout during middle and older ages compared with whites, which appears, particularly in men, to be partly related to higher urate levels in middle-aged blacks. C1 [Maynard, Janet W.] US FDA, Silver Spring, MD USA. [Maynard, Janet W.; Gelber, Allan C.; Baer, Alan N.] Johns Hopkins Sch Med, Div Rheumatol, Baltimore, MD USA. [McAdams-DeMarco, Mara A.; Kao, Linda; Gelber, Allan C.; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [McAdams-DeMarco, Mara A.; Law, Andrew] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. RP McAdams-DeMarco, MA (reprint author), 2024 East Monument St,Suite B-319, Baltimore, MD 21287 USA. EM mmcadams@jhsph.edu OI McAdams-DeMarco, Mara/0000-0003-3013-925X FU National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN 268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; Arthritis National Research Foundation; American Federation for Aging Research; Takeda Pharmaceuticals North America, Inc. FX This work was supported by Takeda Pharmaceuticals North America, Inc. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by the National Heart, Lung, and Blood Institute (contracts HHSN268201100005C, HHSN268201100006C, HHSN 268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). M.A.M.-D. was jointly funded by the Arthritis National Research Foundation and the American Federation for Aging Research. NR 41 TC 13 Z9 14 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 2014 VL 179 IS 5 BP 576 EP 583 DI 10.1093/aje/kwt299 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AB8HB UT WOS:000332029800008 PM 24335384 ER PT J AU Fang, JL Han, T Wu, QG Beland, FA Chang, CW Guo, L Fuscoe, JC AF Fang, Jia-Long Han, Tao Wu, Qiangen Beland, Frederick A. Chang, Ching-Wei Guo, Lei Fuscoe, James C. TI Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine SO ARCHIVES OF TOXICOLOGY LA English DT Article DE AZT; Gene expression; Microarray; Thymidine kinase 1; UDP-glucuronosyltransferase 2B7 ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN LYMPHOBLASTOID-CELLS; IN-VITRO EXPOSURE; T-LYMPHOID CELLS; TELOMERASE ACTIVITY; CYCLE PROGRESSION; REVERSE-TRANSCRIPTASE; INDUCED CYTOTOXICITY; THYMIDINE KINASE-1; AZIDOTHYMIDINE AZT AB Zidovudine (3'-azido-3'-deoxythymidine; AZT) is the most widely used nucleoside reverse transcriptase inhibitor for the treatment of AIDS patients and prevention of mother-to-child transmission of HIV-1. Previously, we demonstrated that AZT had significantly greater growth inhibitory effects upon the human liver carcinoma cell line HepG2 as compared to the immortalized human liver cell line THLE2. We have now used gene expression profiling to determine the molecular pathways associated with toxicity in both cell lines. HepG2 cells were incubated with 0, 2, 20, or 100 mu M AZT for 2 weeks; THLE2 cells were treated with 0, 50, 500, or 2,500 mu M AZT, concentrations that were equi-toxic to those used in the HepG2 cells. After the treatment, total RNA was isolated and subjected to microarray analysis. Global analysis of gene expression, with a false discovery rate a parts per thousand currency sign0.01 and a fold change a parts per thousand yen1.5, indicated that 6- to 70-fold more genes were differentially expressed in a significant concentration-dependent manner in HepG2 cells when compared to THLE2 cells. Comparative analysis indicated that 7 % of these genes were common to both cell lines. Among the common differentially expressed genes, 70 % changed in the same direction, most of which were associated with cell death and survival, cell cycle, cell growth and proliferation, and DNA replication, recombination, and repair. As determined by the uptake of [methyl-H-3]AZT, the intracellular levels of total AZT were approximately twofold higher in THLE2 cells than in HepG2 cells. The expression of thymidine kinase 1 (TK1) and UDP-glucuronosyltransferase 2B7 (UGT2B7) genes that regulate the metabolic activation and deactivation of AZT, respectively, was increased in HepG2 cells but decreased in THLE2 cells after treatment with AZT. This differential response in AZT metabolism was confirmed by real-time PCR, western blotting, and/or enzymatic assays. These data indicate that molecular pathways involved with cell death and survival, cell cycle, cell growth and proliferation, and DNA replication, recombination, and repair are involved in the toxicities associated with AZT in both human cell lines, and that the difference in expression of TK1 and UGT2B7 in response to AZT treatment in HepG2 cells and THLE2 cells might explain why HepG2 cells are more sensitive than THLE2 cells to the toxicity of AZT. C1 [Fang, Jia-Long; Wu, Qiangen; Beland, Frederick A.; Guo, Lei] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Han, Tao; Fuscoe, James C.] Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. [Chang, Ching-Wei] Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. RP Fang, JL (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM jia-long.fang@fda.hhs.gov RI Wu, Qiangen/F-7581-2014 OI Wu, Qiangen/0000-0002-7595-2837 FU Division of Biochemical Toxicology at the National Center for Toxicological Research; National Center for Toxicological Research; US Food and Drug Administration; National Toxicology Program, National Institute of Environmental Health Sciences [FDA IAG: 224-07-0007, NIH Y1ES1027] FX Qiangen Wu was supported by an appointment to the Postgraduate Research Program in the Division of Biochemical Toxicology at the National Center for Toxicological Research administered by Oak Ridge Institute for Science Education through an interagency agreement between the US Department of Energy and the FDA. This research was supported through an interagency agreement between the National Center for Toxicological Research, US Food and Drug Administration and the National Toxicology Program, National Institute of Environmental Health Sciences. (FDA IAG: 224-07-0007; NIH Y1ES1027). NR 62 TC 4 Z9 4 U1 1 U2 15 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5761 EI 1432-0738 J9 ARCH TOXICOL JI Arch. Toxicol. PD MAR PY 2014 VL 88 IS 3 BP 609 EP 623 DI 10.1007/s00204-013-1169-3 PG 15 WC Toxicology SC Toxicology GA AB2WQ UT WOS:000331653200007 PM 24292225 ER PT J AU Kumari, S Crim, RL Kulkarni, A Audet, SA Mdluli, T Murata, H Beeler, JA AF Kumari, Sangeeta Crim, Roberta Lynne Kulkarni, Ashwin Audet, Susette A. Mdluli, Thembi Murata, Haruhiko Beeler, Judy A. TI Development of a Luciferase Immunoprecipitation System Assay To Detect IgG Antibodies against Human Respiratory Syncytial Virus Nucleoprotein SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; REDUCTION NEUTRALIZATION TEST; HUMAN METAPNEUMOVIRUS; MONOCLONAL-ANTIBODY; ENZYME IMMUNOASSAYS; F-GLYCOPROTEIN; MUMPS-VIRUS; PROTEIN; INFECTION; IMMUNOGENICITY AB The nucleoprotein of respiratory syncytial virus (RSV-N) is immunogenic and elicits an IgG response following infection. The RSV-N gene was cloned into a mammalian expression vector, pREN2, and the expressed luciferase-tagged protein (Ruc-N) detected anti-RSV-N-specific IgG antibodies using a high-throughput immunoprecipitation method (the luciferase immunoprecipitation system [LIPS]-N-RSV assay). The specificity of the assay was evaluated using monoclonal antibodies (MAbs) and monospecific pre-and postimmunization rabbit antisera. Blood serum samples from chimpanzees and humans with proven/probable RSV infection were also tested. The pre- and postimmunization serum samples from rabbits given human metapneumovirus (HMPV) or measles virus were negative when tested by the LIPS-N-RSV assay, while antisera obtained after immunization with either the RSV-A or RSV-B strain gave positive signals in a dose-dependent manner. RSV-N MAb 858-3 gave a positive signal in the LIPS-N-RSV assay, while MAbs against other paramyxovirus nucleoproteins or RSV-F or RSV-G did not. Serum samples from chimpanzees simultaneously immunized with vaccinia-RSV-F and vaccinia-RSV-G recombinant viruses were negative in the LIPS-NRSV assay; however, anti-RSV-N IgG responses were detected following subsequent RSV challenge. Seven of the 12 infants who were seronegative at 9 months of age had detectable anti-RSV-N antibodies when they were retested at 15 to 18 months of age. The LIPS-N-RSV assay detects specific anti-RSV-N IgG responses that may be used as a biomarker of RSV infection. C1 [Kumari, Sangeeta; Crim, Roberta Lynne; Kulkarni, Ashwin; Audet, Susette A.; Mdluli, Thembi; Beeler, Judy A.] US FDA, Lab Pediat & Resp Virus Dis, Div Viral Prod, Off Vaccines Res & Review,CBER, Bethesda, MD 20014 USA. [Murata, Haruhiko] US FDA, Lab DNA Viruses, Div Viral Prod, Off Vaccines Res & Review,CBER, Bethesda, MD 20014 USA. RP Beeler, JA (reprint author), US FDA, Lab Pediat & Resp Virus Dis, Div Viral Prod, Off Vaccines Res & Review,CBER, Bethesda, MD 20014 USA. EM judy.beeler@fda.hhs.gov NR 29 TC 2 Z9 2 U1 3 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAR PY 2014 VL 21 IS 3 BP 383 EP 390 DI 10.1128/CVI.00594-13 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AB8JT UT WOS:000332036900015 PM 24403526 ER PT J AU Kolibab, K Yang, A Parra, M Derrick, SC Morris, SL AF Kolibab, K. Yang, A. Parra, M. Derrick, S. C. Morris, S. L. TI Time to Detection of Mycobacterium tuberculosis Using the MGIT 320 System Correlates with Colony Counting in Preclinical Testing of New Vaccines SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID GROWTH-INHIBITION; BCG AB Clinical studies have suggested that the enumeration of mycobacteria by using automated liquid systems is a faster and simpler alternative to quantitative cultures. Here, we show that the time to detection of M. tuberculosis growth as measured with the MGIT 320 liquid culture system inversely correlates with CFU determinations from culture on solid media and that mycobacterial quantification using the MGIT system is faster and easier to perform than CFU plating. C1 [Kolibab, K.; Yang, A.; Parra, M.; Derrick, S. C.; Morris, S. L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Morris, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM sheldon.morris@fda.hhs.gov NR 20 TC 3 Z9 3 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAR PY 2014 VL 21 IS 3 BP 453 EP 455 DI 10.1128/CVI.00742-13 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AB8JT UT WOS:000332036900023 PM 24371256 ER PT J AU Hsu, V Vieira, MDT Zhao, P Zhang, L Zheng, JH Nordmark, A Berglund, EG Giacomini, KM Huang, SM AF Hsu, Vicky Vieira, Manuela de L. T. Zhao, Ping Zhang, Lei Zheng, Jenny Huimin Nordmark, Anna Berglund, Eva Gil Giacomini, Kathleen M. Huang, Shiew-Mei TI Towards Quantitation of the Effects of Renal Impairment and Probenecid Inhibition on Kidney Uptake and Efflux Transporters, Using Physiologically Based Pharmacokinetic Modelling and Simulations SO CLINICAL PHARMACOKINETICS LA English DT Article ID PROTEIN-OVERLOAD PROTEINURIA; ORGANIC ANION TRANSPORTERS; TISSUE DISTRIBUTION; IN-VITRO; CEFUROXIME; OSELTAMIVIR; EXPRESSION; CIDOFOVIR; FIBROSIS; CELLS AB The kidney is a major drug-eliminating organ. Renal impairment or concomitant use of transporter inhibitors may decrease active secretion and increase exposure to a drug that is a substrate of kidney secretory transporters. However, prediction of the effects of patient factors on kidney transporters remains challenging because of the multiplicity of transporters and the lack of understanding of their abundance and specificity. The objective of this study was to use physiologically based pharmacokinetic (PBPK) modelling to evaluate the effects of patient factors on kidney transporters. Models for three renally cleared drugs (oseltamivir carboxylate, cidofovir and cefuroxime) were developed using a general PBPK platform, with the contributions of net basolateral uptake transport (T (up,b)) and apical efflux transport (T (eff,a)) being specifically defined. We demonstrated the practical use of PBPK models to: (1) define transporter-mediated renal secretion, using plasma and urine data; (2) inform a change in the system-dependent parameter (a parts per thousand yen10-fold reduction in the functional 'proximal tubule cells per gram kidney') in severe renal impairment that is responsible for the decreased secretory transport activities of test drugs; (3) derive an in vivo, plasma unbound inhibition constant of T (up,b) by probenecid (a parts per thousand currency sign1 mu M), based on observed drug interaction data; and (4) suggest a plausible mechanism of probenecid preferentially inhibiting T (up,b) in order to alleviate cidofovir-induced nephrotoxicity. C1 [Hsu, Vicky; Vieira, Manuela de L. T.; Zhao, Ping; Zhang, Lei; Zheng, Jenny Huimin; Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Nordmark, Anna; Berglund, Eva Gil] Swedish Med Prod Agcy, Uppsala, Sweden. [Giacomini, Kathleen M.] Univ Calif San Francisco, Sch Pharm, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Giacomini, Kathleen M.] Univ Calif San Francisco, Sch Med, Dept Bioengn & Therapeut Sci, San Francisco, CA USA. RP Zhao, P (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ping.zhao@fda.hhs.gov FU US Food and Drug Administration's (FDA's) Medical Countermeasures initiative FX The authors gratefully acknowledge Professor Amin Rostami-Hodjegan (from the University of Manchester, Manchester, UK) and Drs Sibylle Neuhoff and Masoud Jamei (from Simcyp Ltd, Sheffield, UK) for their scientific input. This research was supported by the US Food and Drug Administration's (FDA's) Medical Countermeasures initiative. Dr Vicky Hsu was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA. No official support or endorsement by the FDA or the Medical Products Agency is intended or should be inferred. NR 31 TC 21 Z9 21 U1 0 U2 5 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 EI 1179-1926 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD MAR PY 2014 VL 53 IS 3 BP 283 EP 293 DI 10.1007/s40262-013-0117-y PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB2XO UT WOS:000331655700007 PM 24214317 ER PT J AU Pacanowski, MA Leptak, C Zineh, I AF Pacanowski, M. A. Leptak, C. Zineh, I. TI Next-Generation Medicines: Past Regulatory Experience and Considerations for the Future SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID DRUG DEVELOPMENT AB Application of personalized medicine in drug development and regulation has been limited by similar logistical, informatics, and cultural barriers that limit use of pharmacogenetics in the clinic. An additional challenge is coordinated codevelopment of new drugs and diagnostic tests. Nevertheless, the impact of personalized medicine strategies (e. g., pharmacogenomics) is being realized. We highlight some of our experiences to date and considerations for the development of the next generation of targeted therapies. C1 [Pacanowski, M. A.; Zineh, I.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Leptak, C.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Pacanowski, MA (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM michael.pacanowski@fda.hhs.gov NR 7 TC 9 Z9 10 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 IS 3 BP 247 EP 249 DI 10.1038/clpt.2013.222 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB6GW UT WOS:000331886600009 PM 24548989 ER PT J AU Arya, V Yang, X Balimane, P Chinn, L Hinderling, P Vaidyanathan, J Zur, AA Wittwer, MB Zhang, L AF Arya, V. Yang, X. Balimane, P. Chinn, L. Hinderling, P. Vaidyanathan, J. Zur, A. A. Wittwer, M. B. Zhang, L. TI CREATININE AS AN ENDOGENOUS MARKER FOR RENAL FUNCTION-EMERGING ROLE OF TRANSPORTERS IN THE OVERALL ASSESSMENT OF RENAL TOXICITY. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Arya, V.; Yang, X.; Balimane, P.; Chinn, L.; Hinderling, P.; Vaidyanathan, J.; Zhang, L.] US FDA, CDER, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. [Zur, A. A.; Wittwer, M. B.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, ORISE, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S65 EP S65 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800190 ER PT J AU Burkhart, K Abernethy, D Jackson, D AF Burkhart, K. Abernethy, D. Jackson, D. TI PREDICTING ADVERSE EVENTS BASED UPON A DRUG'S MOLECULAR TARGET PROFILE SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Burkhart, K.; Abernethy, D.] US FDA, Silver Spring, MD USA. [Jackson, D.] Mol Hlth, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S59 EP S59 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800175 ER PT J AU Hsu, V Vieira, MD Zhao, P Zhang, L Zheng, J Nordmark, A Berglund, EG Giacomini, KM Huang, SM AF Hsu, V. Vieira, M. de L. T. Zhao, P. Zhang, L. Zheng, J. Nordmark, A. Berglund, E. Gil Giacomini, K. M. Huang, S. -M. TI PBPK MODELS OF RENALLY ELIMINATED DRUGS AND THEIR APPLICATION IN EVALUATING THE EFFECT OF PATIENT FACTORS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Hsu, V.; Vieira, M. de L. T.; Zhao, P.; Zhang, L.; Zheng, J.; Huang, S. -M.] US FDA, Silver Spring, MD USA. [Nordmark, A.; Berglund, E. Gil] Swedish MPA, Uppsala, Sweden. [Giacomini, K. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S57 EP S57 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800167 ER PT J AU Hsu, V Grillo, J Pan, Y Zhao, P Bullock, J AF Hsu, V. Grillo, J. Pan, Y. Zhao, P. Bullock, J. TI EVALUATING THE EFFECT OF SUBJECT DEMOGRAPHICS ON RIVAROXABAN EXPOSURE USING PBPK MODELING SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Hsu, V.; Grillo, J.; Pan, Y.; Zhao, P.; Bullock, J.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S19 EP S19 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800054 ER PT J AU Hsu, V Vieira, MDT Zhao, P Zhang, L Zheng, J Nordmark, A Berglund, EG Giacomini, KM Huang, SM AF Hsu, V. Vieira, M. de L. T. Zhao, P. Zhang, L. Zheng, J. Nordmark, A. Berglund, E. Gil Giacomini, K. M. Huang, S. -M. TI PBPK MODELS OF RENALLY ELIMINATED DRUGS AND THEIR APPLICATION IN EVALUATING THE EFFECT OF PATIENT FACTORS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Hsu, V.; Vieira, M. de L. T.; Zhao, P.; Zhang, L.; Zheng, J.; Huang, S. -M.] US FDA, Silver Spring, MD USA. [Nordmark, A.; Berglund, E. Gil] Swedish MPA, Uppsala, Sweden. [Giacomini, K. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S8 EP S8 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800021 ER PT J AU Kim, N Li, L Kim, M Davis, D Huang, SM Zhang, L Zhao, P Soule, L Willett, G Yu, C AF Kim, N. Li, L. Kim, M. Davis, D. Huang, S. -M. Zhang, L. Zhao, P. Soule, L. Willett, G. Yu, C. TI PHARMACOKINETIC AND PHARMACODYNAMIC ASSESSMENTS FOR HORMONAL CONTRACEPTIVE DRUG-DRUG INTERACTIONS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Kim, N.; Li, L.; Kim, M.; Davis, D.; Huang, S. -M.; Zhang, L.; Zhao, P.; Soule, L.; Willett, G.; Yu, C.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S20 EP S20 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800056 ER PT J AU Lin, L Chen, EC Hsu, V Zhao, P Zhang, L Huang, SM Giacomini, KM AF Lin, L. Chen, E. C. Hsu, V. Zhao, P. Zhang, L. Huang, S. M. Giacomini, K. M. TI MECHANISMS OF NEURAMINIDASE INHIBITOR TRANSPORT ACROSS THE BLOOD-BRAIN BARRIER SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Lin, L.; Chen, E. C.; Giacomini, K. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hsu, V.; Zhao, P.; Zhang, L.; Huang, S. M.] US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S70 EP S70 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800205 ER PT J AU Pan, Y Grillo, J Hsu, V Zhang, L Sinha, V Huang, SM Zhao, P AF Pan, Y. Grillo, J. Hsu, V. Zhang, L. Sinha, V. Huang, S. -M. Zhao, P. TI APPLICATION OF THE FDA PBPK KNOWLEDGEBASE IN EVALUATING MODEL PREDICTABILITY FOR DRUG-DRUG INTERACTIONS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Pan, Y.; Grillo, J.; Hsu, V.; Zhang, L.; Sinha, V.; Huang, S. -M.; Zhao, P.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S102 EP S103 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800301 ER PT J AU Ramamoorthy, A Pacanowski, MA Bull, J Zhang, L AF Ramamoorthy, A. Pacanowski, M. A. Bull, J. Zhang, L. TI RACE/ETHNICITY BASED PRESCRIBING RECOMMENDATIONS FOR NEW MOLECULAR ENTITIES: SURVEY OF RECENT APPROVALS. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Ramamoorthy, A.; Pacanowski, M. A.; Bull, J.; Zhang, L.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S62 EP S62 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800183 ER PT J AU Sarntivijai, S Lin, Y Blair, E Burkhart, K He, Y Omenn, GS Athey, BD Abernethy, DR AF Sarntivijai, S. Lin, Y. Blair, E. Burkhart, K. He, Y. Omenn, G. S. Athey, B. D. Abernethy, D. R. TI THE ONTOLOGICAL REPRESENTATION OF ADVERSE EVENTS WITH COMPOSITE SYMPTOMS: EXPANDING ONTOLOGY OF ADVERSE EVENTS TO DESCRIBE DRUG-INDUCED CARDIOTOXICITY. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Sarntivijai, S.; Burkhart, K.; Abernethy, D. R.] US FDA, Silver Spring, MD USA. [Lin, Y.; He, Y.] Univ Michigan, Dept Microbiol & Immunol, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. [Blair, E.] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA. [Omenn, G. S.; Athey, B. D.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S67 EP S67 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800197 ER PT J AU Sarntivijai, S Hur, J Ozgur, A Burkhart, K He, Y Omenn, GS Athey, BD Abernethy, DR AF Sarntivijai, S. Hur, J. Ozgur, A. Burkhart, K. He, Y. Omenn, G. S. Athey, B. D. Abernethy, D. R. TI PREDICTING GENE INTERACTIONS OF TYROSINE KINASE INHIBITORS INDUCED CARDIOTOXICITY WITH THE ONTOLOGY OF ADVERSE EVENTS-ASSISTED BIOINFORMATICS APPROACH. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Sarntivijai, S.; Burkhart, K.; Abernethy, D. R.] US FDA, Silver Spring, MD USA. [Hur, J.] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI USA. [Ozgur, A.] Bogazici Univ, Dept Comp Sci, Istanbul, Turkey. [He, Y.] Univ Michigan, Sch Med, Unit Lab Anim Med, Ann Arbor, MI USA. [Omenn, G. S.; Athey, B. D.] Univ Michigan, Sch Med, Dept Computat Med & Bioinformat, Ann Arbor, MI USA. RI Ozgur, Arzucan/I-3147-2012 OI Ozgur, Arzucan/0000-0001-8376-1056 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S67 EP S68 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800198 ER PT J AU Younis, IR AF Younis, I. R. TI RETURN ON INVESTMENT OF PHARMACOKINETIC STUDIES IN SUBJECTS WITH MILD RENAL IMPAIRMENT. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Younis, I. R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S64 EP S65 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800189 ER PT J AU Zhang, L Wu, F Lee, S Zhao, H Zhang, L AF Zhang, L. Wu, F. Lee, S. Zhao, H. Zhang, L. TI PH-DEPENDENT DRUG-DRUG INTERACTIONS: POTENTIAL IMPLICATIONS FOR NEW DRUG DEVELOPMENT. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Zhang, L.; Wu, F.; Lee, S.; Zhao, H.; Zhang, L.] US FDA, CDER, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. [Wu, F.] US FDA, CDER, Off Translat Sci, ORISE, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S65 EP S65 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800191 ER PT J AU Zheng, S Snoeys, J Schmidt, S Lesko, L Zhao, P AF Zheng, S. Snoeys, J. Schmidt, S. Lesko, L. Zhao, P. TI INHIBITOR MODELS IN PREDICTING DRUG-DRUG INTERACTIONS USING PBPK: A CASE STUDY WITH FLUVOXAMINE. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-22, 2014 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Zheng, S.; Schmidt, S.; Lesko, L.] Univ Florida, Ctr Pharmacometr & Syst Pharmacol, Orlando, FL USA. [Snoeys, J.] Janssen Pharmaceut Co Johnson & Johnson, Beerse, Belgium. [Zhao, P.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Silver Spring, MD USA. RI Zheng, Songmao/M-4718-2014 OI Zheng, Songmao/0000-0002-7727-0928 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2014 VL 95 SU 1 BP S95 EP S95 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB7ZL UT WOS:000332009800278 ER PT J AU Zhang, YY Li, HX Chen, YY Fang, H Yu, YN Liu, J Jing, ZW Wang, Z Wang, YY AF Zhang, Ying-Ying Li, Hai-Xia Chen, Yin-Ying Fang, Hong Yu, Ya-Nan Liu, Jun Jing, Zhi-Wei Wang, Zhong Wang, Yong-Yan TI Convergent and Divergent Pathways Decoding Hierarchical Additive Mechanisms in Treating Cerebral Ischemia-Reperfusion Injury SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Additive effect; Pharmacological mechanism; Ingenuity Pathway Analysis; Cerebral ischemia; Drug combination ID CELL-DEATH; SIGNALING PATHWAYS; BRAIN-DAMAGE; NEURODEGENERATIVE DISORDERS; NETWORK PHARMACOLOGY; THROMBOLYTIC THERAPY; LIPID-METABOLISM; EMBOLIC STROKE; EXCITOTOXICITY; DISEASE AB Introduction Cerebral ischemia is considered to be a highly complex disease resulting from the complicated interplay of multiple pathways. Disappointedly, most of the previous studies were limited to a single gene or a single pathway. The extent to which all involved pathways are translated into fusing mechanisms of a combination therapy is of fundamental importance. Aims We report an integrative strategy to reveal the additive mechanism that a combination (BJ) of compound baicalin (BA) and jasminoidin (JA) fights against cerebral ischemia based on variation of pathways and functional communities. Results We identified six pathways of BJ group that shared diverse additive index from 0.09 to 1, which assembled broad cross talks from seven pathways of BA and 16 pathways of JA both at horizontal and vertical levels. Besides a total of 60 overlapping functions as a robust integration background among the three groups based on significantly differential subnetworks, additive mechanism with strong confidence by networks altered functions. Conclusions These results provide strong evidence that the additive mechanism is more complex than previously appreciated, and an integrative analysis of pathways may suggest an important paradigm for revealing pharmacological mechanisms underlying drug combinations. C1 [Zhang, Ying-Ying; Chen, Yin-Ying; Yu, Ya-Nan; Liu, Jun; Jing, Zhi-Wei; Wang, Zhong; Wang, Yong-Yan] China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing 100700, Peoples R China. [Li, Hai-Xia] China Acad Chinese Med Sci, Guanganmen Hosp, Beijing 100700, Peoples R China. [Fang, Hong] US FDA, Z Tech Corp, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Wang, Z (reprint author), China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing 100700, Peoples R China. EM zhonw@vip.sina.com FU National 11th Five-years-plan Supporting RD Project [2006BAI08B04-06] FX This work was supported by National 11th Five-years-plan Supporting R&D Project (2006BAI08B04-06). NR 51 TC 7 Z9 9 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 EI 1755-5949 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PD MAR PY 2014 VL 20 IS 3 BP 253 EP 263 DI 10.1111/cns.12205 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AB1GZ UT WOS:000331540800008 PM 24351012 ER PT J AU Garzel, B Yang, H Zhang, L Huang, SM Polli, JE Wang, HB AF Garzel, Brandy Yang, Hui Zhang, Lei Huang, Shiew-Mei Polli, James E. Wang, Hongbing TI The Role of Bile Salt Export Pump Gene Repression in Drug-Induced Cholestatic Liver Toxicity SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CONSTITUTIVE ANDROSTANE RECEPTOR; SANDWICH-CULTURED HEPATOCYTES; PREGNANE-X-RECEPTOR; NUCLEAR RECEPTOR; EXPRESSION; INJURY; HEPATOTOXICITY; IDENTIFICATION; INHIBITION; MECHANISM AB The bile salt export pump (BSEP, ABCB11) is predominantly responsible for the efflux of bile salts, and disruption of BSEP function is often associated with altered hepatic homeostasis of bile acids and cholestatic liver injury. Accumulating evidence suggests that many drugs can cause cholestasis through interaction with hepatic transporters. To date, a relatively strong association between drug-induced cholestasis and attenuated BSEP activity has been proposed. However, whether repression of BSEP transcription would contribute to drug-induced cholestasis is largely unknown. In this study, we selected 30 drugs previously reported as BSEP inhibitors to evaluate their effects on BSEP expression, farnesoid X receptor (FXR) activation, and correlations to clinically reported liver toxicity. Our results indicate that of the 30 BSEP inhibitors, five exhibited potent repression of BSEP expression (>= 60% repression), ten were moderate repressors (20-60% repression), whereas others had negligible effects (<= 20% repression). Of importance, two drugs (troglitazone and benzbromarone), previously withdrawn from the market because of liver injury, are among the potent repressors. Further investigation of the five potent repressors revealed that transcriptional repression of BSEP by lopinavir and troglitazone may occur through their interaction with FXR, whereas others are via FXR-independent yet unidentified pathways. Our data suggest that in addition to functional inhibition, repression of BSEP expression may play an important role in drug-induced cholestatic liver toxicity. Thus, a combination of the two would reveal a more accurate prediction of drug-induced cholestasis than does either repression or inhibition alone. C1 [Garzel, Brandy; Yang, Hui; Polli, James E.; Wang, Hongbing] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Zhang, Lei; Huang, Shiew-Mei] US FDA, CDER, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. RP Wang, HB (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 20 Penn St, Baltimore, MD 21201 USA. EM hwang@rx.umaryland.edu FU US Food and Drug Administration [U01FD004320]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK061652] FX This work was supported by the US Food and Drug Administration [Award U01FD004320] and the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant DK061652]. The manuscript reflects the views of the authors and should not be construed to represent FDA's views or policies. NR 29 TC 10 Z9 10 U1 2 U2 8 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR PY 2014 VL 42 IS 3 BP 318 EP 322 DI 10.1124/dmd.113.054189 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AB2ID UT WOS:000331615500002 PM 24335466 ER PT J AU Gheorghiade, M Vaduganathan, M Greene, SJ Mentz, RJ Adams, KF Anker, SD Arnold, M Baschiera, F Cleland, JGF Cotter, G Fonarow, GC Giordano, C Metra, M Misselwitz, F Muhlhofer, E Nodari, S Peacock, WF Pieske, BM Sabbah, HN Sato, N Shah, MR Stockbridge, NL Teerlink, JR van Veldhuisen, DJ Zalewski, A Zannad, F Butler, J AF Gheorghiade, Mihai Vaduganathan, Muthiah Greene, Stephen J. Mentz, Robert J. Adams, Kirkwood F., Jr. Anker, Stefan D. Arnold, Malcolm Baschiera, Fabio Cleland, John G. F. Cotter, Gadi Fonarow, Gregg C. Giordano, Christopher Metra, Marco Misselwitz, Frank Muehlhofer, Eva Nodari, Savina Peacock, W. Frank Pieske, Burkert M. Sabbah, Hani N. Sato, Naoki Shah, Monica R. Stockbridge, Norman L. Teerlink, John R. van Veldhuisen, Dirk J. Zalewski, Andrew Zannad, Faiez Butler, Javed TI Site selection in global clinical trials in patients hospitalized for heart failure: perceived problems and potential solutions SO HEART FAILURE REVIEWS LA English DT Article DE Heart failure; Site selection; Clinical trials; FDA ID QUALITY-OF-CARE; UNITED-STATES; OPTIMIZE-HF; END-POINTS; OUTCOMES; ASSOCIATION; RATIONALE; REGISTRY; PROGRAM; DESIGN AB There are over 1 million hospitalizations for heart failure (HF) annually in the United States alone, and a similar number has been reported in Europe. Recent clinical trials investigating novel therapies in patients with hospitalized HF (HHF) have been negative, and the post-discharge event rate remains unacceptably high. The lack of success with HHF trials stem from problems with understanding the study drug, matching the drug to the appropriate HF subgroup, and study execution. Related to the concept of study execution is the importance of including appropriate study sites in HHF trials. Often overlooked issues include consideration of the geographic region and the number of patients enrolled at each study center. Marked differences in baseline patient co-morbidities, serum biomarkers, treatment utilization and outcomes have been demonstrated across geographic regions. Furthermore, patients from sites with low recruitment may have worse outcomes compared to sites with higher enrollment patterns. Consequently, sites with poor trial enrollment may influence key patient end points and likely do not justify the costs of site training and maintenance. Accordingly, there is an unmet need to develop strategies to identify the right study sites that have acceptable patient quantity and quality. Potential approaches include, but are not limited to, establishing a pre-trial registry, developing site performance metrics, identifying a local regionally involved leader and bolstering recruitment incentives. This manuscript summarizes the roundtable discussion hosted by the Food and Drug Administration between members of academia, the National Institutes of Health, industry partners, contract research organizations and academic research organizations on the importance of selecting optimal sites for successful trials in HHF. C1 [Gheorghiade, Mihai; Greene, Stephen J.] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA. [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Mentz, Robert J.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC USA. [Adams, Kirkwood F., Jr.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Anker, Stefan D.] Ctr Clin & Basic Res, IRCCS San Raffaele, Rome, Italy. [Arnold, Malcolm] Univ Western Ontario, Div Cardiol, London, ON, Canada. [Baschiera, Fabio] Novartis Pharma AG, Basel, Switzerland. [Cleland, John G. F.] Castle Hill Hosp, Kingston Upon Hull, Yorks, England. [Cotter, Gadi] Momentum Res Inc, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Giordano, Christopher] Quintiles, Cardiovasc & Metab Therapeut Delivery Unit, Durham, NC USA. [Metra, Marco; Nodari, Savina] Univ Brescia, Div Cardiol, Brescia, Italy. [Misselwitz, Frank] Bayer Healthcare Pharmaceut, Berlin, Germany. [Muehlhofer, Eva] Bayer Vital GmbH, Leverkusen, Germany. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. [Pieske, Burkert M.] Med Univ Graz, Div Cardiol, Graz, Austria. [Sabbah, Hani N.] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. [Sato, Naoki] Musahi Kosugi Hosp, Nippon Med Sch, Dept Internal Med & Cardiol, Kanagawa, Japan. [Shah, Monica R.] NHLBI, Bethesda, MD 20892 USA. [Stockbridge, Norman L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Teerlink, John R.] Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Zalewski, Andrew] Novartis Pharmaceut, E Hanover, NJ USA. [Zannad, Faiez] Univ Lorraine, CHU Cardiol, INSERM, CIC 9501, Nancy, France. [Zannad, Faiez] Univ Lorraine, CHU Cardiol, U961, Nancy, France. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI van Veldhuisen, Dirk Jan/E-8967-2014; OI Metra, Marco/0000-0001-6691-8568; Cleland, John/0000-0002-1471-7016 FU Vifor International; PsiOxus Therapeutics; Bayer Healthcare; Corthera; Novartis; Cytokinetics; Amgen; NIH; Roche Diagnostics; BG Medicine; Pfizer; Sorbent; Vifor; GE Healthcare; Medtronic FX Mihai Gheorghiade: Consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm S. A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical and Trevena Therapeutics. Stefan D Anker: Consultant for Vifor International, Amgen, Bayer, Bosch GmbH, PsiOxus Therapeutics, Professional Dietetics, Novartis. Research support from Vifor International, PsiOxus Therapeutics. John G F Cleland: Received an honorarium from Bayer for an advisory board. Gregg C Fonarow: Consultant to Medtronic, Novartis, Gambro and Ortho-McNeill. Marco Metra: Received honoraria from Bayer, Corthera, Novartis, and Servier for speeches or participation in advisory boards/steering committees. Frank Misselwitz and Eva Muhlhofer: Employed by Bayer Healthcare. Hani N Sabbah: Research Grants and Consultant to Bayer Healthcare. Naoki Sato: Consultant to Chugai Pharmaceutical Company and honoraria from Daiichi-Sankyo, Otsuka, Philips Respironics, Astellas, Ono, Eisai, Chugai, Mitsubishi-Tanabe, Sanofi-Aventis, and Novartis pharmaceuticals. John R Teerlink: Research Grants from Corthera, Novartis, Cytokinetics, Amgen, NIH. Consultant to Amgen, Anexon, Cardio3 Bioscience, CardioMEMS, Cytokinetics, Gambro, Johnson and Johnson, Merck, NovaCardia, Novartis, Scios, Sorbent Therapeutics, St. Jude Medical, Teva, Theravance, Trevena. Faiez Zannad: Reports receiving consultant honoraria from Servier, Pfizer, Novartis, ResMed, Takeda, and Boston Scientific, and that his institution receives research grants from Roche Diagnostics and BG Medicine. Dirk J van Veldhuisen: Board Membership fees from Amgen, BG Medicine, Pfizer, Sorbent and Vifor. Javed Butler: Consultant to Cardiomems, Trevena, Bayer Healthcare, Takeda, Gambro, Ono Pharma, and Amgen; Events Committee for WorldHeart, Corthera, Abbott Vascular, Celladon, Research Support, NIH, GE Healthcare and Medtronic. All other authors have no conflicts of interest to declare. NR 30 TC 24 Z9 24 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 EI 1573-7322 J9 HEART FAIL REV JI Heart Fail. Rev. PD MAR PY 2014 VL 19 IS 2 BP 135 EP 152 DI 10.1007/s10741-012-9361-8 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB5JY UT WOS:000331825900001 PM 23099992 ER PT J AU Tereshchenk, LG Rizzi, P Mewton, N Volpe, GJ Murthy, S Strauss, DG Liu, CY Marchlinski, FE Spooner, P Berger, RD Kellman, P Lima, JAC AF Tereshchenk, Larisa G. Rizzi, Patricia Mewton, Nathan Volpe, Gustavo Jardim Murthy, Sindhoora Strauss, David G. Liu, Chia Y. Marchlinski, Francis E. Spooner, Peter Berger, Ronald D. Kellman, Peter Lima, Joao A. C. TI Infiltrated atrial fat characterizes underlying atrial fibrillation substrate in patients at risk as defined by the ARIC atrial fibrillation risk score SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Atrial fibrillation; Cardiac magnetic resonance; Intraatrial infiltrated fat; Risk score ID QRS-T ANGLE; LIPOMATOUS HYPERTROPHY; INTERATRIAL SEPTUM; ADIPOSE-TISSUE; MAGNETIC-RESONANCE; PERICARDIAL FAT; FOLLOW-UP; HEART; ABLATION; POPULATION AB Background: It is known that expanded epicardial fat is associated with atrial fibrillation (AF). However, infiltrated intraatrial fat has not been previously quantified in individuals at risk as determined by the ARIC AF risk score. Methods: Patients in sinus rhythm (N = 90, age 57 +/- 10 years; 55 men [63.2%]), in 3 groups at risk of AF as determined by the ARIC AF risk score [low (<= 11 points; n = 15), moderate (12-18 points; n = 40), high (>= 19 points; n = 23) risk of AF], and paroxysmal AF (n = 12) underwent cardiac magnetic resonance study. Intraatrial and epicardial fat was analyzed with a Dark-blood DIR-prepared Fat-Water-separated sequence in the horizontal longitudinal axis. OsiriX DICOMviewer (Geneva, Switzerland) was used to quantify the intraatrial fat area. Width of the cephalad portion of the interatrial septum was measured at the level of the fossa ovalis. Results: Intraatrial fat monotonically increasedwith growing AF risk in study groups (low AF risk 16 > 4 vs. moderate AF risk 32 +/- 18 vs. high AF risk 81 +/- 83mm(2); ANOVA P= 0.012). Log-transformed intraatrial fat predicted ARIC AF risk score inmultivariate ordered probit regression after adjustment for sex, race, left and right atrial area indices, and body mass index (beta-coefficient 0.50 [95% CI 0.03-0.97]; P = 0.037), whereas epicardial fat did not. Interatrial septumwidth showed similar association (3.0 +/- 1.4 vs. 5.0 +/- 1.8 vs. 7.1 +/- 2.7mm; ANOVA P< 0.001; adjusted beta-coefficient 2.80 [95% CI 1.19-4.41]; P = 0.001). Conclusions: Infiltrated intraatrial fat characterizes evolving substrate in individuals at risk of AF. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Tereshchenk, Larisa G.; Rizzi, Patricia; Mewton, Nathan; Volpe, Gustavo Jardim; Liu, Chia Y.; Spooner, Peter; Berger, Ronald D.; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Murthy, Sindhoora] Johns Hopkins Univ, Whiting Sch Engn, Baltimore, MD 21205 USA. [Strauss, David G.] US FDA, Silver Spring, MD USA. [Marchlinski, Francis E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Kellman, Peter] NHLBI, NIH, Bethesda, MD 20892 USA. RP Tereshchenk, LG (reprint author), Carnegie 568,600 N Wolfe St, Baltimore, MD 21287 USA. EM lteresh1@jhmi.edu OI Tereshchenko, Larisa/0000-0002-6976-1313 FU NHLBI NIH HHS [R01 HL118277, P20HL101397, P20 HL101397] NR 31 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAR 1 PY 2014 VL 172 IS 1 BP 196 EP 201 DI 10.1016/j.ijcard.2014.01.012 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB3WT UT WOS:000331721600134 PM 24485635 ER PT J AU Imanishi, M Rotstein, DS Reimschuessel, R Schwensohn, CA Woody, DH Davis, SW Hunt, AD Arends, KD Achen, M Cui, J Zhang, Y Denny, LF Phan, QN Joseph, LA Tuite, CC Tataryn, JR Behravesh, CB AF Imanishi, Maho Rotstein, David S. Reimschuessel, Renate Schwensohn, Colin A. Woody, Dillard H., Jr. Davis, Samuel W. Hunt, April D. Arends, Katherine D. Achen, Maya Cui, Jing Zhang, Yan Denny, Lynn F. Phan, Quyen N. Joseph, Lavin A. Tuite, Carla C. Tataryn, Joanne R. Behravesh, Casey Barton TI Outbreak of Salmonella enterica serotype Infantis infection in humans linked to dry dog food in the United States and Canada, 2012 SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID PET FOOD; TREATS; PRODUCTS; UPDATE AB Case Description-In April 2012, Salmonella enterica serotype Infantis was detected in an unopened bag of dry dog food collected during routine retail surveillance. PulseNet, a national bacterial subtyping network, identified humans with Salmonella Infantis infection with the same genetic fingerprint as the dog food sample. Clinical Findings-An outbreak investigation identified 53 ill humans infected with the outbreak strain during January 1 to July 5, 2012, in 21 states and 2 provinces in Canada; 20 (38%) were children <= 2 years old, and 12 of 37 (32%) were hospitalized. Of 21 ill people who remembered the dog food brand, 12 (57%) reported a brand produced at a plant in Gaston, SC. Traceback investigations also identified that plant. The outbreak strain was isolated from bags of dry dog food and fecal specimens obtained from dogs that lived with ill people and that ate the implicated dry dog food. Treatment and Outcome-The plant was closed temporarily for cleaning and disinfection. Sixteen brands involving > 27,000 metric tons (> 30,000 tons) of dry dog and cat food were recalled. Thirty-one ill dogs linked to recalled products were reported through the FDA consumer complaint system. Clinical Relevance-A one-health collaborative effort on epidemiological, laboratory, and traceback investigations linked dry dog foods produced at a plant to illnesses in dogs and humans. More efforts are needed to increase awareness among pet owners, health-care professionals, and the pet food industry on the risk of illness in pets and their owners associated with dry pet foods and treats. C1 [Imanishi, Maho; Schwensohn, Colin A.; Joseph, Lavin A.; Behravesh, Casey Barton] CDC, Natl Ctr Emerging & Zoonot Infect Dis, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA. [Rotstein, David S.; Tuite, Carla C.] US FDA, Off Coordinated Outbreak Response & Evaluat Netwo, College Pk, MD 20740 USA. [Reimschuessel, Renate] US FDA, Ctr Vet Med, Res Off, Vet Lab Investigat & Response Network, Laurel, MD 20708 USA. [Woody, Dillard H., Jr.] US FDA, Ctr Vet Med, Div Compliance, Rockville, MD 20855 USA. [Davis, Samuel W.] South Carolina Dept Agr, Columbia, SC 29211 USA. [Hunt, April D.] Michigan Dept Agr & Rural Dev, Pesticide & Plant Pest Management Div, Lansing, MI 48933 USA. [Arends, Katherine D.] Michigan Dept Community Hlth, Communicable Dis Div, Lansing, MI 48933 USA. [Achen, Maya] Ohio Dept Agr, Consumer Protect Lab, Reynoldsburg, OH 43068 USA. [Cui, Jing; Zhang, Yan] Ohio Dept Agr, Anim Dis Diagnost Lab, Reynoldsburg, OH 43068 USA. [Denny, Lynn F.] Ohio Dept Hlth, Bur Infect Dis, Columbus, OH 43215 USA. [Phan, Quyen N.] Connecticut Dept Publ Hlth, Epidemiol & Emerging Infect Program, Hartford, CT 06134 USA. [Tataryn, Joanne R.] Publ Hlth Agcy Canada, Ctr Food Borne Environm & Zoonot Infect Dis, Outbreak Management Div, Saskatoon, SK S7N 5B4, Canada. RP Behravesh, CB (reprint author), CDC, Natl Ctr Emerging & Zoonot Infect Dis, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA. EM CBartonBehravesh@cdc.gov NR 34 TC 9 Z9 9 U1 3 U2 20 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 EI 1943-569X J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD MAR 1 PY 2014 VL 244 IS 5 BP 545 EP 553 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA AB4RS UT WOS:000331778200008 PM 24548229 ER PT J AU Mishina, EV Hoffman, AC AF Mishina, Elena V. Hoffman, Allison C. TI Clinical Pharmacology Research Strategy for Dissolvable Tobacco Products SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID REDUCED EXPOSURE PRODUCTS; SMOKELESS TOBACCO; NICOTINE CONTENT; N-NITROSAMINES; MOIST SNUFF; DELIVERY; PHARMACOKINETICS; METABOLITES; WITHDRAWAL; ADDICTION AB Introduction: Dissolvable tobacco products (DTPs) are relatively new to the market. Some researchers and manufacturers describe them as finely ground tobacco that has been compressed into sticks, strips, and orbs that dissolve or disintegrate in the mouth and do not require spitting. While the pharmacokinetic profiles of nicotine and other tobacco-associated compounds and pharmacological effects of these products are complex, their clinical pharmacology has not been systematically evaluated. We reviewed the scientific literature regarding the known pharmacokinetic (PK) characteristics and pharmacodynamic (PD) effects of DTPs with the purpose of identifying research gaps and informing future studies. To evaluate current knowledge of the pharmacological properties of DTPs; to assess their similarities and differences with other tobacco products, especially smokeless tobacco products, and Food and Drug Administrationapproved nicotine replacement therapies; to identify gaps in existing information; and to propose a strategy for future clinical pharmacology studies of DTPs. We reviewed the peer-reviewed literature and generated research questions for future clinical pharmacology studies. Data on the PK and PD of DTPs are sparse and inconsistent. The results of existing studies are limited and inconclusive, and their interpretation is complicated by methodological and/or study design issues. This review identifies a need for larger, comprehensive, and prospectively designed studies that include PK/PD measurements and data analyses. We propose a research agenda for future DTP studies related to the clinical pharmacology of nicotine, its metabolites, tobacco-specific nitrosamines, and other toxic compounds. C1 [Mishina, Elena V.; Hoffman, Allison C.] Ctr Tobacco Prod Food & Drug Adm, Off Sci, Rockville, MD 20850 USA. RP Mishina, EV (reprint author), Ctr Tobacco Prod Food & Drug Adm, Off Sci, 9200 Corp Blvd, Rockville, MD 20850 USA. EM elena.mishina@fda.hhs.gov NR 43 TC 2 Z9 2 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAR PY 2014 VL 16 IS 3 BP 253 EP 262 DI 10.1093/ntr/ntt182 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA AB6BQ UT WOS:000331872900001 PM 24253379 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Postmarketing safety of biologics and biological devices SO SPINE JOURNAL LA English DT Review DE Postmarketing safety; Adverse events; FDA; Medical devices; Biological products; Surveillance; FAERS; MAUDE ID ADVERSE EVENTS AB BACKGROUND CONTEXT: Regardless of study design, the approval process of biologics and biological devices cannot identify every possible safety concern. Postmarketing safety surveillance can provide information based on real-world use of medical products in heterogeneous populations and is critical for identifying potentially serious adverse events, events that are too rare to be detected during premarketing studies, late complications, and events involving individuals or uses that were not evaluated in clinical trials. PURPOSE: To review why adverse event reporting is important and how the information is used, with emphasis on the points that are most applicable for surgeons and other spine professionals. METHODS: This is an overview of postmarketing safety surveillance. RESULTS: Review of adverse event reports has resulted in safety notifications, label changes, and publications regarding the safety of biologics and biological devices, such as the risk of airway compromise after the use of recombinant human bone morphogenetic protein in cervical spine fusion, the occurrence of a fatal air embolism after the use of a fibrin sealant that had been applied with a spray device, and infections after allograft transplantation of human tissues. CONCLUSIONS: In light of the rapid development of new biologics, postmarketing surveillance is imperative for ensuring that these products are as safe as possible. By reporting adverse events, surgeons and other health care professionals play a key role in improving and refining our understanding of the safety of biologics. Published by Elsevier Inc. C1 US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, HFM 222,1401 Rockville Pike, Rockville, MD 20852 USA. EM jane.woo@fda.hhs.gov NR 29 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD MAR PY 2014 VL 14 IS 3 SI SI BP 560 EP 565 DI 10.1016/j.spinee.2013.09.056 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AB3TY UT WOS:000331714300023 PM 24342704 ER PT J AU Kuhar, DT Struble, KA Henderson, DK AF Kuhar, David T. Struble, Kimberly A. Henderson, David K. TI Selecting an Antiretroviral Regimen for Human Immunodeficiency Virus Postexposure Prophylaxis in the Occupational Setting Reply SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Letter ID EMTRICITABINE; TOLERABILITY; RALTEGRAVIR; ADHERENCE; TENOFOVIR; SAFETY C1 [Kuhar, David T.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Struble, Kimberly A.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Henderson, David K.] NIH, Off Deputy Director Clin Care, Ctr Clin, Bethesda, MD 20892 USA. RP Kuhar, DT (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, 1600 Clifton Rd NE,MS A-31, Atlanta, GA 30333 USA. EM jto7@cdc.gov FU Intramural CDC HHS [CC999999] NR 7 TC 1 Z9 1 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAR 1 PY 2014 VL 35 IS 3 BP 328 EP 329 DI 10.1086/675350 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AA6MH UT WOS:000331211900023 PM 24521605 ER PT J AU Basch, E Trentacosti, AM Burke, LB Kwitkowski, V Kane, RC Autio, KA Papadopoulos, E Stansbury, JP Kluetz, PG Smith, H Justice, R Pazdur, R AF Basch, Ethan Trentacosti, Ann Marie Burke, Laurie B. Kwitkowski, Virginia Kane, Robert C. Autio, Karen A. Papadopoulos, Elektra Stansbury, James P. Kluetz, Paul G. Smith, Harry Justice, Robert Pazdur, Richard TI Pain Palliation Measurement in Cancer Clinical Trials SO CANCER LA English DT Article ID PATIENT-REPORTED OUTCOMES; IMMPACT RECOMMENDATIONS; LABELING CLAIMS; END-POINTS; BACK-PAIN; SEVERITY; CUTPOINTS; INVENTORY; APPROVAL; MODERATE C1 [Basch, Ethan] Univ N Carolina, Canc Outcomes Res Program, Chapel Hill, NC 27599 USA. [Trentacosti, Ann Marie; Burke, Laurie B.; Kwitkowski, Virginia; Kane, Robert C.; Papadopoulos, Elektra; Stansbury, James P.; Kluetz, Paul G.; Justice, Robert; Pazdur, Richard] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Autio, Karen A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Smith, Harry] US FDA, Off Commun, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Basch, E (reprint author), Univ N Carolina, Canc Outcomes Res Program, 170 Manning Dr,CB 7305,Phys Off Bldg,Suite 3185, Chapel Hill, NC 27599 USA. EM ebasch@med.unc.edu FU National Cancer Institute; Department of Defense [W81XWH-11-1-0639] FX Subsequent to the completion of this work and his Guest Worker position at the US Food and Drug Administration, Dr. Basch has provided uncompensated input regarding analysis and publication of patient-reported outcome assessments for Exelixis and Janssen, and served as the uncompensated study chair for a prostate cancer pain trial by Exelixis. Dr. Basch's research is supported by grants from the National Cancer Institute and the Department of Defense (grant W81XWH-11-1-0639). This work does not represent the views or opinions of the Department of Defense. NR 34 TC 6 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAR 1 PY 2014 VL 120 IS 5 BP 761 EP 767 PG 7 WC Oncology SC Oncology GA AB0AM UT WOS:000331454200018 PM 24375398 ER PT J AU Senior, JR AF Senior, John R. TI New biomarkers for drug-induced liver injury: are they really better? what do they diagnose? SO LIVER INTERNATIONAL LA English DT Editorial Material ID MECHANISTIC BIOMARKERS; TRANSAMINASE ACTIVITY; HEPATOTOXICITY; HUMANS C1 US FDA, Off Pharmacovigilance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Senior, JR (reprint author), US FDA, Off Pharmacovigilance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 14 TC 4 Z9 4 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-3223 EI 1478-3231 J9 LIVER INT JI Liver Int. PD MAR PY 2014 VL 34 IS 3 BP 325 EP 327 DI 10.1111/liv.12384 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 304KB UT WOS:000330744400001 PM 25839081 ER PT J AU Agyingi, L Mayr, LM Kinge, T Orock, GE Ngai, J Asaah, B Mpoame, M Hewlett, I Nyambi, P AF Agyingi, Lucy Mayr, Luzia M. Kinge, Thompson Orock, George Enow Ngai, Johnson Asaah, Bladine Mpoame, Mbida Hewlett, Indira Nyambi, Phillipe TI The Evolution of HIV-1 Group M Genetic Variability in Southern Cameroon is Characterized by Several Emerging Recombinant Forms of CRF02_AG and Viruses With Drug Resistance Mutations SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE Cameroon; genetic diversity; unique recombinant forms; drug resistance mutations ID EQUATORIAL RAIN-FORESTS; WEST CENTRAL-AFRICA; INTERSUBTYPE RECOMBINANTS; SEQUENCE ALIGNMENT; VIRAL VARIANTS; TYPE-1 HIV-1; SUBTYPE-A; DIVERSITY; STRAINS; NAIVE AB The HIV epidemic in Cameroon is marked by a broad genetic diversity dominated by circulating recombinant forms (CRFs). Studies performed more than a decade ago in urban settings of Southern Cameroon revealed a dominance of the CRF02_AG and clade A variants in >90% of the infected subjects; however, little is known about the evolving viral variants circulating in this region. To document circulating HIV viral diversity, four regions of the viral genome (gag, PR, reverse transcriptase, env) in 116 HIV-1 positive individuals in Limbe, Southern Cameroon, were PCR-amplified. Sequences obtained at the RT and protease regions were analyzed for mutations that conferred drug resistance using the Stanford Drug Resistance Database. The present study reveals a broad genetic diversity characterized by several unique recombinant forms (URF) accounting for 36% of infections, 48.6% of patients infected with CRF02_AG, and the emergence of CRF22_01A1 in 7.2% of patients. Three out of 15 (20%) treated patients and 13 out of 93 (13.9%) drug naive patients harbor drug resistance mutations to RT inhibitors, while 3.2% of drug naive patients harbor drug resistance mutations associated with protease inhibitors. The high proportion (13.9%) of drug resistance mutations among the drug naive patients reveals the ongoing transmission of these viruses in this region of Cameroon and highlights the need for drug resistance testing before starting treatment for patients infected with HIV-1. J. Med. Virol. 86:385-393, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Agyingi, Lucy; Mpoame, Mbida] Univ Dschang, Fac Sci, West Region, Cameroon. [Agyingi, Lucy; Mayr, Luzia M.; Nyambi, Phillipe] NYU, Sch Med, Dept Pathol, New York, NY 10010 USA. [Kinge, Thompson] Limbe Reg Hosp, Limbe, South West Regi, Cameroon. [Orock, George Enow] Buea Reg Hosp, Buea, South West Regi, Cameroon. [Ngai, Johnson; Asaah, Bladine] Med Diagnost Ctr, Yaounde, Center Region, Cameroon. [Hewlett, Indira] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Nyambi, Phillipe] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA. RP Nyambi, P (reprint author), NYU, Sch Med, VA Med Ctr, Dept Pathol, 423 East 23rd St,Room 18124N, New York, NY 10010 USA. EM phillipe.nyambi@nyumc.org FU Department of Veterans Affairs; National Institute of Allergy and Infectious Diseases (NIAID) [AI083142]; National Cancer Institute (NCI) [CA153726]; Fogarty International Center (FIC) [TW001409] FX Grant sponsor: Department of Veterans Affairs (Merit Review Award and the Research Enhancement Program); Grant sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Grant number: AI083142; Grant sponsor: National Cancer Institute (NCI); Grant number: CA153726; Grant sponsor: Fogarty International Center (FIC); Grant number: TW001409 NR 42 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0146-6615 EI 1096-9071 J9 J MED VIROL JI J. Med. Virol. PD MAR PY 2014 VL 86 IS 3 BP 385 EP 393 DI 10.1002/jmv.23846 PG 9 WC Virology SC Virology GA 286IJ UT WOS:000329461000003 PM 24248638 ER PT J AU Colin-Gonzalez, AL Luna-Lopez, A Konigsberg, M Ali, SF Pedraza-Chaverri, J Santamaria, A AF Colin-Gonzalez, A. L. Luna-Lopez, A. Koenigsberg, M. Ali, S. F. Pedraza-Chaverri, J. Santamaria, A. TI EARLY MODULATION OF THE TRANSCRIPTION FACTOR NRF2 IN RODENT STRIATAL SLICES BY QUINOLINIC ACID, A TOXIC METABOLITE OF THE KYNURENINE PATHWAY SO NEUROSCIENCE LA English DT Article DE kynurenine pathway; oxidative stress; antioxidant defense; excitotoxicity; Nrf2 ID OXIDATIVE STRESS; NEURODEGENERATIVE DISORDERS; HUNTINGTONS-DISEASE; BEHAVIORAL ALTERATIONS; INDUCED NEUROTOXICITY; RESPONSE ELEMENT; HEME OXYGENASE-1; S-ALLYLCYSTEINE; RAT-BRAIN; ANTIOXIDANT AB Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor involved in the orchestration of antioxidant responses. Although its pharmacological activation has been largely hypothesized as a promising tool to ameliorate the progression of neurodegenerative events, the actual knowledge about its modulation in neurotoxic paradigms remains scarce. In this study, we investigated the early profile of Nrf2 modulation in striatal slices of rodents incubated in the presence of the toxic kynurenine pathway metabolite, quinolinic acid (QUIN). Tissue slices from rats and mice were obtained and used throughout the experiments in order to compare inter-species responses. Nuclear Nrf2 protein levels and oxidative damage to lipids were compared. Time-and concentration-response curves of all markers were explored. Nrf2 nuclear activation was corroborated through phase 2 antioxidant protein expression. The effects of QUIN on Nrf2 modulation and oxidative stress were also compared between slices of wild-type (Nrf2(+/+)) and Nrf2 knock-out (Nrf2(-/-)) mice. The possible involvement of the N-methyl-D-aspartate receptor (NMDAr) in the Nrf2 modulation and lipid peroxidation was further explored in mice striatal slices. In rat striatal slices, QUIN stimulated the Nrf2 nuclear translocation. This effect was accompanied by augmented lipid peroxidation. In the mouse striatum, QUIN per se exerted an induction of Nrf2 factor only at 1 h of incubation, and a concentration-response effect on lipid peroxidation after 3 h of incubation. QUIN stimulated the striatal content of phase 2 enzymes. Nrf2(-/-) mice were slightly more responsive than Nrf2(+/+) mice to the QUINinduced oxidative damage, and completely unresponsive to the NMDAr antagonist MK-801 when tested against QUIN. Findings of this study indicate that: (1) Nrf2 is modulated in rodent striatal tissue in response to QUIN; (2) Nrf2(-/-) striatal tissue was moderately more vulnerable to oxidative damage than the Wt condition; and (3) early Nrf2 up-regulation reflects a compensatory response to the QUIN-induced oxidative stress in course as part of a general defense system, whereas Nrf2 down-regulation might contribute to more intense oxidative cell damage. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Colin-Gonzalez, A. L.; Santamaria, A.] Inst Nacl Neurol & Neurocirugia SSA, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. [Luna-Lopez, A.] Inst Nacl Geriatria SSA, Mexico City, DF, Mexico. [Koenigsberg, M.] Univ Autonoma Metropolitana Iztapalapa, DCBS, Dept Ciencias Salud, Mexico City 09340, DF, Mexico. [Ali, S. F.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Pedraza-Chaverri, J.] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico. RP Santamaria, A (reprint author), Inst Nacl Neurol & Neurocirugia SSA, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. EM absada@yahoo.com FU CONACyT [205648]; CONACyT-Mexico [239954] FX This work was supported by CONACyT Grant 205648 (A. S.). We thank Dr. Antonio Cuadrado (Autonomous University of Madrid, Spain) for technical help to conduct the experiments with striatal mice slices. We are also grateful to Dr. Ismael Torres and Dr. Enrique Pinzon for the technical support with the experimental animals. Ana Laura Colin-Gonzalez is scholarship holder of CONACyT-Mexico (239954). NR 46 TC 6 Z9 6 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD FEB 28 PY 2014 VL 260 BP 130 EP 139 DI 10.1016/j.neuroscience.2013.12.025 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 302IM UT WOS:000330598100012 PM 24361737 ER PT J AU Shim, YK Rachel, JM Ghia, P Boren, J Abbasi, F Dagklis, A Venable, G Kang, J Degheidy, H Plapp, FV Vogt, RF Menitove, JE Marti, GE AF Shim, Youn K. Rachel, Jane M. Ghia, Paolo Boren, Jeff Abbasi, Fatima Dagklis, Antonis Venable, Geri Kang, Jiyeon Degheidy, Heba Plapp, Fred V. Vogt, Robert F. Menitove, Jay E. Marti, Gerald E. TI Monoclonal B-cell lymphocytosis in healthy blood donors: an unexpectedly common finding SO BLOOD LA English DT Article ID NATURAL-HISTORY; FLOW-CYTOMETRY; LEUKEMIA; PREVALENCE; CLL; TRANSPLANTATION; EXPRESSION; CLONES; SHOWS; RISK AB Circulating monoclonal B cells may be detected in healthy adults, a condition called monoclonal B-cell lymphocytosis (MBL). MBL has also been identified in donated blood, but no systematic study of blood donors has been reported. Using sensitive and specific laboratory methods, we detected MBL in 149 (7.1%; 95% confidence interval, 6.0% to 8.3%) of 2098 unique donors ages 45 years or older in a Midwestern US regional blood center between 2010 and 2011. Most of the 149 donors had low-count MBL, including 99 chronic lymphocytic leukemia-like (66.4%), 22 atypical (14.8%), and 19 CD5(-) (12.8%) immunophenotypes. However, 5 donors (3.4%) had B-cell clonal counts above 500 cells per mu L, including 3 with 1693 to 2887 cells per mL; the clone accounted for nearly all their circulating B cells. Four donors (2.7%) had 2 distinct MBL clones. Of 51 MBL samples in which immunoglobulin heavy chain (IGH) V-D-J genotypes could be determined, 71% and 29% used IGHV3-and IGHV4-family genes, respectively. Sequencing revealed 82% with somatic hypermutation, whereas 18% had >98% germ-line identity, including 5 with entirely germ-line sequences. In conclusion, MBL prevalence is much higher in blood donors than previously reported, and although uncommon, the presence of high-count MBL warrants further investigations to define the biological fate of the transfused cells in recipients. C1 [Shim, Youn K.] Agcy Tox Subst & Dis Registry, Div Toxicol & Human Hlth Sci, Atlanta, GA 30341 USA. [Rachel, Jane M.; Boren, Jeff; Plapp, Fred V.] St Lukes Hosp, Dept Pathol, Kansas City, MO USA. [Ghia, Paolo; Dagklis, Antonis] Univ Vita Salute San Raffaele, Div Mol Oncol, Milan, Italy. [Ghia, Paolo; Dagklis, Antonis] Univ Vita Salute San Raffaele, Dept Oncohematol, Milan, Italy. [Ghia, Paolo; Dagklis, Antonis] Ist Sci San Raffaele, Milan, Italy. [Abbasi, Fatima; Degheidy, Heba] US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Venable, Geri; Menitove, Jay E.] Community Blood Ctr, Kansas City, MO USA. [Kang, Jiyeon] MeSun Hlth Serv, Lawrenceville, GA USA. [Vogt, Robert F.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. [Marti, Gerald E.] US FDA, Div Immunol & Hematol Devices, Off Vitro Diagnost Device Evaluat & Safety, Silver Spring, MD USA. RP Shim, YK (reprint author), Agcy Tox Subst & Dis Registry, Div Toxicol & Human Hlth Sci, 4770 Buford Highway, Atlanta, GA 30341 USA. EM yshim@cdc.gov RI Ghia, Paolo/K-7138-2016 OI Ghia, Paolo/0000-0003-3750-7342 FU Agency for Toxic Substances and Disease Registry; Associazione Italiana per la Ricerca sul Cancro AIRC [9965]; Ricerca Finalizzata; Ministero della salute, Roma; Progetti di Ricerca di Interesse Nazionale - Ministero Istruzione, Universita e Ricerca, Roma, Italy FX This project was supported in part by the Agency for Toxic Substances and Disease Registry and in part by the Associazione Italiana per la Ricerca sul Cancro AIRC (Investigator Grant and Special Program Molecular Clinical Oncology - 5 per mille #9965), Ricerca Finalizzata 2010, Ministero della salute, Roma; Progetti di Ricerca di Interesse Nazionale - Ministero Istruzione, Universita e Ricerca, Roma, Italy. NR 33 TC 22 Z9 22 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD FEB 27 PY 2014 VL 123 IS 9 BP 1319 EP 1326 DI 10.1182/blood-2013-08-523704 PG 8 WC Hematology SC Hematology GA AH0VR UT WOS:000335839300014 PM 24345750 ER PT J AU Egan, AG Blind, E Dunder, K de Graeff, PA Hummer, BT Bourcier, T Rosebraugh, C AF Egan, Amy G. Blind, Eberhard Dunder, Kristina de Graeff, Pieter A. Hummer, B. Timothy Bourcier, Todd Rosebraugh, Curtis TI Pancreatic Safety of Incretin-Based Drugs - FDA and EMA Assessment SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material AB After evaluating a safety signal regarding pancreatitis and pancreatic cancer in patients using incretin-based drugs, the Food and Drug Administration and the European Medicines Agency conclude that assertions of a causal association are inconsistent with the data. With approximately 25.8 million diabetic patients in the United States and 33 million in the European Union alone, the growing prevalence of diabetes worldwide poses a major public health challenge. Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are committed to ensuring the safety of drug products marketed for the treatment of diabetes, and postmarketing reports of pancreatitis and pancreatic cancer in patients taking certain antidiabetic medications have been of concern to both agencies. Working in parallel, the agencies have reviewed nonclinical toxicology studies, clinical trial data, and epidemiologic data pertaining to blood glucose-lowering ... C1 [Egan, Amy G.; Hummer, B. Timothy; Bourcier, Todd; Rosebraugh, Curtis] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Blind, Eberhard] European Med Agcy, London, England. [Dunder, Kristina] Lakemedelsverket, Uppsala, Sweden. [de Graeff, Pieter A.] Dutch Med Evaluat Board, Utrecht, Netherlands. RP Egan, AG (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 5 TC 173 Z9 178 U1 0 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 27 PY 2014 VL 370 IS 9 BP 794 EP 797 DI 10.1056/NEJMp1314078 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AB8AR UT WOS:000332013000004 PM 24571751 ER PT J AU He, X Sahiner, B Gallas, BD Chen, WJ Petrick, N AF He, Xin Sahiner, Berkman Gallas, Brandon D. Chen, Weijie Petrick, Nicholas TI Computerized characterization of lung nodule subtlety using thoracic CT images SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE computer-aided detection; lung nodules; lung CT; subtlety; agreement ID DATABASE CONSORTIUM; AIDED DETECTION; PULMONARY NODULES; ASSOCIATION; SEGMENTATION; ACCURACY; RESOURCE; MASSES; LIDC AB The goal of this work is to design computerized image analysis techniques for automatically characterizing lung nodule subtlety in CT images. Automated subtlety estimation methods may help in computer-aided detection (CAD) assessment by quantifying dataset difficulty and facilitating comparisons among different CAD algorithms. A dataset containing 813 nodules from 499 patients was obtained from the Lung Image Database Consortium. Each nodule was evaluated by four radiologists regarding nodule subtlety using a 5-point rating scale (1: most subtle). We developed a 3D technique for segmenting lung nodules using a prespecified initial ROI. Texture and morphological features were automatically extracted from the segmented nodules and their margins. The dataset was partitioned into trainers and testers using a 1: 1 ratio. An artificial neural network (ANN) was trained with average reader subtlety scores as the reference. Effective features for characterizing nodule subtlety were selected based on the training set using the ANN and a stepwise feature selection method. The performance of the classifier was evaluated using prediction probability (PK) as an agreement measure, which is considered a generalization of the area under the receiver operating characteristic curve when the reference standard is multi-level. Using an ANN classifier trained with a set of 2 features (selected from a total of 30 features), including compactness and average gray value, the test concordance between computer scores and the average reader scores was 0.789 +/- 0.014. Our results show that the proposed method had strong agreement with the average of subtlety scores provided by radiologists. C1 [He, Xin; Sahiner, Berkman; Gallas, Brandon D.; Chen, Weijie; Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP He, X (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM xin.he@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 18 TC 4 Z9 4 U1 0 U2 13 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 21 PY 2014 VL 59 IS 4 BP 897 EP 910 DI 10.1088/0031-9155/59/4/897 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AB6YZ UT WOS:000331937500008 PM 24487773 ER PT J AU Alosh, M Bretz, F Huque, M AF Alosh, Mohamed Bretz, Frank Huque, Mohammad TI Advanced multiplicity adjustment methods in clinical trials SO STATISTICS IN MEDICINE LA English DT Article DE multiple testing; -propagation; adaptive alpha; gatekeeping; graphical methods ID CLOSED-TESTING PROCEDURES; SECONDARY END-POINTS; FIXED-SEQUENCE; GATEKEEPING STRATEGIES; BONFERRONI PROCEDURE; CONFIDENCE-REGIONS; DOSE-RESPONSE; HYPOTHESES; OBJECTIVES; MULTISTAGE AB During the last decade, many novel approaches for addressing multiplicity problems arising in clinical trials have been introduced in the literature. These approaches provide great flexibility in addressing given clinical trial objectives and yet maintain strong control of the familywise error rate. In this tutorial article, we review multiple testing strategies that are related to the following: (a) recycling local significance levels to test hierarchically ordered hypotheses; (b) adapting the significance level for testing a hypothesis to the findings of testing previous hypotheses within a given test sequence, also in view of certain consistency requirements; (c) grouping hypotheses into hierarchical families of hypotheses along with recycling the significance level between those families; and (d) graphical methods that permit repeated recycling of the significance level. These four different methodologies are related to each other, and we point out some connections as we describe and illustrate them. By contrasting the main features of these approaches, our objective is to help practicing statisticians to select an appropriate method for their applications. In this regard, we discuss how to apply some of these strategies to clinical trial settings and provide algorithms to calculate critical values and adjusted p-values for their use in practice. The methods are illustrated with several numerical examples. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Alosh, Mohamed] US FDA, Div Biometr 3, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. [Bretz, Frank] Novartis Pharma AG, Basel, Switzerland. [Bretz, Frank] Hannover Med Sch, Hannover, Germany. [Huque, Mohammad] US FDA, Off Biostat, OTS, CDER, Silver Spring, MD USA. RP Alosh, M (reprint author), US FDA, Div Biometr 3, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. EM Mohamed.Alosh@fda.hhs.gov RI Bretz, Frank/F-6927-2014 NR 67 TC 10 Z9 10 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD FEB 20 PY 2014 VL 33 IS 4 BP 693 EP 713 DI 10.1002/sim.5974 PG 21 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA AA0QS UT WOS:000330802300012 PM 24105821 ER PT J AU Laksanalamai, P Huang, BX Sabo, J Burall, LS Zhao, SH Bates, J Datta, AR AF Laksanalamai, Pongpan Huang, Bixing Sabo, Jonathan Burall, Laurel S. Zhao, Shaohua Bates, John Datta, Atin R. TI Genomic Characterization of Novel Listeria monocytogenes Serotype 4b Variant Strains SO PLOS ONE LA English DT Article ID FIELD GEL-ELECTROPHORESIS; TANDEM-REPEAT ANALYSIS; MULTIPLEX PCR; UNITED-STATES; NUMBER; OUTBREAK; IDENTIFICATION; VIRULENCE; MICROARRAYS; DIVERSITY AB Over 90% of the human listeriosis cases are caused by Listeria monocytogenes serotypes 1/2a, 1/2b and 4b strains. As an alternative to antigen-antibody based serotyping, a PCR-based method for serogrouping has been developed and validated. In this communication, we report an in-depth analysis of five 4b variant strains, four clinical isolates from Australia and one environmental isolate from USA. Although these five strains were serotype 4b by classical serotyping method, the serogrouping PCR profiles of these strains show the presence of a 1/2a-3a specific amplicon in addition to the standard 4b-4d-4e specific amplicons. These strains were further analyzed by pulsed field gel electrophoresis, binary gene typing, multilocus variable-number-tandem-repeat analysis and a high density pan-genomic Listeria microarray. Using these sub-typing results, the clinical isolates were grouped into two distinct genomic groups-one of which could be part of an unidentified outbreak. The microarray results when compared with our database of other 4b outbreak isolates indicated that the serotype 4b variant strains represent very different genotypic profiles than the known reported 4b outbreak strains representing major epidemic clones. The acquisition of serotype 1/2a gene clusters by the 4b variant strains appears to be independent in origin, spanning large areas of geographical and temporal space and may indicate predisposition of some 4b strains towards accepting DNA from related organisms. C1 [Laksanalamai, Pongpan; Burall, Laurel S.; Datta, Atin R.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Huang, Bixing; Bates, John] Queensland Hlth Forens & Sci Serv, Publ Hlth Microbiol Lab, Coopers Plains, Qld, Australia. [Sabo, Jonathan; Zhao, Shaohua] US FDA, Ctr Vet Med, Laurel, MD USA. RP Datta, AR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM atin.datta@fda.hhs.gov NR 56 TC 4 Z9 4 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 19 PY 2014 VL 9 IS 2 AR e89024 DI 10.1371/journal.pone.0089024 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AB3TA UT WOS:000331711900071 PM 24586485 ER PT J AU Scholl, PF Farris, SM Mossoba, MM AF Scholl, Peter F. Farris, Samantha M. Mossoba, Magdi M. TI Rapid Turbidimetric Detection of Milk Powder Adulteration with Plant Proteins SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE allergen; deterrent; economically motivated adulteration; infrared; legume; mass spectrometry; milk; pea; plant storage protein; protein; protein concentrate; protein isolate; rapid screening; rice; simple; soy; tetra borate; turbidimetry; wheat ID ECONOMICALLY MOTIVATED ADULTERATION; PERFORMANCE LIQUID-CHROMATOGRAPHY; NEAR-INFRARED SPECTROSCOPY; TANDEM MASS-SPECTROMETRY; DAIRY-PRODUCTS; SOYBEAN PROTEINS; CAPILLARY-ELECTROPHORESIS; BIOSENSOR IMMUNOASSAYS; VEGETABLE PROTEINS; CASEIN MICELLES AB Development of assays to screen milk for economically motivated adulteration with foreign proteins has been stalled since 2008 due to strong international reactions to the melamine poisoning incident in China and the surveillance emphasis placed on low molecular weight nitrogen-rich adulterants. New screening assays are still needed to detect high molecular weight foreign protein adulterants and characterize this understudied potential risk. A rapid turbidimetric method was developed to screen milk powder for adulteration with insoluble plant proteins. Milk powder samples spiked with 0.03-3% by weight of soy, pea, rice, and wheat protein isolates were extracted in 96-well plates, and resuspended pellet solution absorbance was measured. Limits of detection ranged from 100 to 200 mu g, or 0.1-0.2% of the sample weight, and adulterant pellets were visually apparent even at similar to 0.1%. Extraction recoveries ranged from 25 to 100%. Assay sensitivity and simplicity indicate that it would be ideally suitable to rapidly screen milk samples in resource poor environments where adulteration with plant protein is suspected. C1 [Scholl, Peter F.; Farris, Samantha M.; Mossoba, Magdi M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Scholl, PF (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 707,Room BE-006, College Pk, MD 20740 USA. EM peter.scholl@fda.hhs.gov OI Scholl, Peter/0000-0002-8870-3266 NR 49 TC 5 Z9 6 U1 2 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD FEB 19 PY 2014 VL 62 IS 7 BP 1498 EP 1505 DI 10.1021/jf405617f PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA AB4SE UT WOS:000331779400009 PM 24484379 ER PT J AU Warfel, JM Merkel, TJ AF Warfel, Jason M. Merkel, Tod J. TI Reply to Domenech de Celles et al.: Infection and transmission of pertussis in the baboon model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID DISEASE C1 [Warfel, Jason M.; Merkel, Tod J.] US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. EM tod.merkel@fda.hhs.gov FU NIH HHS [P40 OD010431, P40 OD010988] NR 5 TC 1 Z9 1 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 2014 VL 111 IS 7 BP E718 EP E718 DI 10.1073/pnas.1324074111 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AA9EL UT WOS:000331396500004 PM 24693544 ER EF