FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mei, Y Simmonett, AC Pickard, FC DiStasio, RA Brooks, BR Shao, YH AF Mei, Ye Simmonett, Andrew C. Pickard, Frank C. DiStasio, Robert A., Jr. Brooks, Bernard R. Shao, Yihan TI Numerical Study on the Partitioning of the Molecular Polarizability into Fluctuating Charge and Induced Atomic Dipole Contributions SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID CLASSICAL DRUDE OSCILLATORS; QUANTUM-MECHANICAL CALCULATIONS; ELECTROSTATIC POTENTIAL FIT; DENSITY-FUNCTIONAL THEORY; PROTEIN-SPECIFIC CHARGES; FORCE-FIELD; DYNAMICS SIMULATIONS; INTERMOLECULAR INTERACTIONS; CONFORMATIONAL DEPENDENCE; BIOMOLECULAR SIMULATION AB In order to carry out a detailed analysis of the molecular static polarizability, which is the response of the molecule to a uniform external electric field, the molecular polarizability was computed using the finite-difference method for 21 small molecules, using density functional theory. Within nine charge population schemes (Lowdin, Mulliken, Becke, Hirshfeld, CM5, Hirshfeld-I, NPA, CHELPG, MK-ESP) in common use, the charge fluctuation contribution is found to dominate the molecular polarizability, with its ratio ranging from 59.9% with the Hirshfeld or CM5 scheme to 96.2% with the Mulliken scheme. The Hirshfeld-I scheme is also used to compute the other contribution to the molecular polarizability coming from the induced atomic dipoles, and the atomic polarizabilities in eight small molecules and water pentamer are found to be highly anisotropic for most atoms. Overall, the results suggest that (a) more emphasis probably should be placed on the charge fluctuation terms in future polarizable force field development and (b) an anisotropic polarizability might be more suitable than an isotropic one in polarizable force fields based entirely or partially on the induced atomic dipoles. C1 [Mei, Ye] E China Normal Univ, State Key Lab Precis Spect, Dept Phys, Shanghai 200062, Peoples R China. [Mei, Ye] E China Normal Univ, Inst Theoret & Computat Sci, Shanghai 200062, Peoples R China. [Mei, Ye] NYU Shanghai, NYU ECNU Ctr Computat Chem, Shanghai 200062, Peoples R China. [Mei, Ye; Simmonett, Andrew C.; Pickard, Frank C.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Rockville, MD 20852 USA. [DiStasio, Robert A., Jr.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA. [Shao, Yihan] Q Chem Inc, Pleasanton, CA 94588 USA. RP Mei, Y (reprint author), E China Normal Univ, State Key Lab Precis Spect, Dept Phys, Shanghai 200062, Peoples R China. EM ymei@phy.ecnu.edu.cn; yihan@q-chem.com RI MEI, Ye/C-5843-2009 OI MEI, Ye/0000-0002-3953-8508 FU National Natural Science Foundation of China [21173082]; China Scholarship Council [201208310344]; NIH Grant [GM096678-02]; DOE Grant [DE-SC0011297]; Intramural Research Program of the NIH, NHLBI FX Y.M. is supported by the National Natural Science Foundation of China (Grant No. 21173082) and the China Scholarship Council (Grant No. 201208310344). Y.S. is supported by NIH Grant GM096678-02 and DOE Grant No. DE-SC0011297. A.C.S, F.C.P. and B.R.B. are supported by the Intramural Research Program of the NIH, NHLBI. Computational resources and services used in this work were partially provided by the LoBoS cluster of the National Institutes of Health. Several charge partitioning schemes in Q-Chem were employed in this study, and Y.S. thanks the Troy van Voorhis group for their implementation of Becke and Hirshfeld charges, Drs. Alek Marenich and Don Truhlar for the implementation of CM5 charges, Dr. Eric Glendening for the implementation of natural population analysis, and the John Herbert group for the implementation of CHELPG charges. Y.S. also thanks Dr. Ramkumar Rajamani for helpful discussions on Hirshfeld charges, Mr. Ka Un Lao and Dr. John Herbert for helpful discussions on iterative Hirshfeld charges, and Dr. Qin Wu for discussions about Becke charges. NR 135 TC 4 Z9 4 U1 5 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD JUN 4 PY 2015 VL 119 IS 22 BP 5865 EP 5882 DI 10.1021/acs.jpca.5b03159 PG 18 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA CK0KD UT WOS:000355893200036 PM 25945749 ER PT J AU Vassilopoulos, A Tominaga, Y Kim, HS Lahusen, T Li, B Yu, H Gius, D Deng, CX AF Vassilopoulos, A. Tominaga, Y. Kim, H-Seok Lahusen, T. Li, B. Yu, H. Gius, D. Deng, C-X TI WEE1 murine deficiency induces hyper-activation of APC/C and results in genomic instability and carcinogenesis SO ONCOGENE LA English DT Article ID CELL-CYCLE CHECKPOINTS; DNA-DAMAGING AGENTS; FISSION YEAST; TYROSINE KINASE; CDC25 PROTEIN; MITOTIC INHIBITOR; G(2) CHECKPOINT; GENE DELETION; CANCER; P53 AB The tyrosine kinase WEE1 controls the timing of entry into mitosis in eukaryotes and its genetic deletion leads to pre-implantation lethality in mice. Here, we show that besides the premature mitotic entry phenotype, Wee1 mutant murine cells fail to complete mitosis properly and exhibit several additional defects that contribute to the deregulation of mitosis, allowing mutant cells to progress through mitosis at the expense of genomic integrity. WEE1 interacts with the anaphase promoting complex, functioning as a negative regulator, and the deletion of Wee1 results in hyper-activation of this complex. Mammary specific knockout mice overcome the DNA damage response pathway triggered by the mis-coordination of the cell cycle in mammary epithelial cells and heterozygote mice spontaneously develop mammary tumors. Thus, WEE1 functions as a haploinsufficient tumor suppressor that coordinates distinct cell division events to allow correct segregation of genetic information into daughter cells and maintain genome integrity. C1 [Vassilopoulos, A.; Tominaga, Y.; Kim, H-Seok; Lahusen, T.; Deng, C-X] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Vassilopoulos, A.; Gius, D.] Northwestern Univ, Feinberg Sch Med, Dept Radiat Oncol, Chicago, IL 60611 USA. [Kim, H-Seok] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea. [Li, B.; Yu, H.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dept Pharmacol, Dallas, TX 75390 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10 Room 9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU NIDDK; NCI [1R01CA152601-01]; DOD [BC093803]; SPORE [P50CA98131]; Hirshberg Foundation for Pancreatic Cancer Research Seed Grant Award; CCR, NIH FX We are grateful for the critical reading and helpful discussion of members of the Deng laboratory. This work was supported in part by the Intramural Research Program of the NIDDK, NCI and CCR, NIH. DG is supported by 1R01CA152601-01 from the NCI, BC093803 from the DOD, SPORE P50CA98131 and a Hirshberg Foundation for Pancreatic Cancer Research Seed Grant Award. Melissa Stauffer, PhD, of Scientific Editing Solutions, provided editorial assistance. NR 59 TC 2 Z9 2 U1 0 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 JUN 4 PY 2015 VL 34 IS 23 BP 3023 EP 3035 DI 10.1038/onc.2014.239 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CK3EX UT WOS:000356100500008 PM 25088202 ER PT J AU Dmitrieva, NI Burg, MB AF Dmitrieva, Natalia I. Burg, Maurice B. TI Elevated Sodium and Dehydration Stimulate Inflammatory Signaling in Endothelial Cells and Promote Atherosclerosis SO PLOS ONE LA English DT Article ID CORONARY-HEART-DISEASE; PLASMA SODIUM; CARDIOVASCULAR-DISEASE; VASCULAR ENDOTHELIUM; MULTIVARIABLE ANALYSIS; LEUKOCYTE RECRUITMENT; BLOOD-PRESSURE; SHEAR-STRESS; SALT INTAKE; RISK-FACTOR AB Cardiovascular diseases (CVDs) are a leading health problem worldwide. Epidemiologic studies link high salt intake and conditions predisposing to dehydration such as low water intake, diabetes and old age to increased risk of CVD. Previously, we demonstrated that elevation of extracellular sodium, which is a common consequence of these conditions, stimulates production by endothelial cells of clotting initiator, von Willebrand Factor, increases its level in blood and promotes thrombogenesis. In present study, by PCR array, using human umbilical vein endothelial cells (HUVECs), we analyzed the effect of high NaCl on 84 genes related to endothelial cell biology. The analysis showed that the affected genes regulate many aspects of endothelial cell biology including cell adhesion, proliferation, leukocyte and lymphocyte activation, coagulation, angiogenesis and inflammatory response. The genes whose expression increased the most were adhesion molecules VCAM1 and E-selectin and the chemoattractant MCP-1. These are key participants in the leukocyte adhesion and transmigration that play a major role in the inflammation and pathophysiology of CVD, including atherosclerosis. Indeed, high NaCl increased adhesion of mononuclear cells and their transmigration through HUVECs monolayers. In mice, mild water restriction that elevates serum sodium by 5 mmol/l, increased VCAM1, E-selectin and MCP-1 expression in mouse tissues, accelerated atherosclerotic plaque formation in aortic root and caused thickening or walls of coronary arteries. Multivariable linear regression analysis of clinical data from the Atherosclerosis Risk in Communities Study (n = 12779) demonstrated that serum sodium is a significant predictor of 10 Years Risk of coronary heart disease. These findings indicate that elevation of extracellular sodium within the physiological range is accompanied by vascular changes that facilitate development of CVD. The findings bring attention to serum sodium as a risk factor for CVDs and give additional support to recommendations for dietary salt restriction and adequate water intake as preventives of CVD. C1 [Dmitrieva, Natalia I.; Burg, Maurice B.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Dmitrieva, NI (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dmitrien@nhlbi.nih.gov RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 FU Intramural Program of National Lung Heart and Blood Institute FX The study was supported by the Intramural Program of National Lung Heart and Blood Institute. NR 69 TC 7 Z9 8 U1 0 U2 5 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 4 PY 2015 VL 10 IS 6 AR UNSP e0128870 DI 10.1371/journal.pone.0128870 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ7TC UT WOS:000355701600069 PM 26042828 ER PT J AU Mahdi, Y Xu, XM Carlson, BA Fradejas, N Gunter, P Braun, D Southon, E Tessarollo, L Hatfield, DL Schweizer, U AF Mahdi, Yassin Xu, Xue-Ming Carlson, Bradley A. Fradejas, Noelia Guenter, Paul Braun, Doreen Southon, Eileen Tessarollo, Lino Hatfield, Dolph L. Schweizer, Ulrich TI Expression of Selenoproteins Is Maintained in Mice Carrying Mutations in SECp43, the tRNA Selenocysteine 1 Associated Protein (Trnau1ap) SO PLOS ONE LA English DT Article ID SECIS ELEMENTS; INCORPORATION MACHINERY; SELENIUM DEFICIENCY; GENETIC-CODE; LIVER; BRAIN; UGA; EXTINCTION; DISRUPTION; INSERTION AB Selenocysteine tRNA 1 associated protein (Trnau1ap) has been characterized as a tRNA([Ser]Sec)-binding protein of 43 kDa, hence initially named SECp43. Previous studies reported its presence in complexes containing tRNA([Ser]Sec) implying a role of SECp43 as a co-factor in selenoprotein expression. We generated two conditionally mutant mouse models targeting exons 3+4 and exons 7+8 eliminating parts of the first RNA recognition motif or of the tyrosine-rich domain, respectively. Constitutive inactivation of exons 3+4 of SECp43 apparently did not affect the mice or selenoprotein expression in several organs. Constitutive deletion of exons 7+8 was embryonic lethal. We therefore generated hepatocyte-specific Secp43 knockout mice and characterized selenoprotein expression in livers of mutant mice. We found no significant changes in the levels of Se-75-labelled hepatic proteins, selenoprotein levels as determined by Western blot analysis, enzymatic activity or selenoprotein mRNA abundance. The methylation pattern of tRNA([Ser]Sec) remained unchanged. Truncated Secp43(Delta 7,8)mRNA increased in Secp43-mutant livers suggesting auto-regulation of Secp43 mRNA abundance. We found no signs of liver damage in Secp433-mutant mice, but neuron-specific deletion of exons 7+8 impaired motor performance, while not affecting cerebral selenoprotein expression or cerebellar development. These findings suggest that the targeted domains in the SECp43 protein are not essential for selenoprotein biosynthesis in hepatocytes and neurons. Whether the remaining second RNA recognition motif plays a role in selenoprotein biosynthesis and which other cellular process depends on SECp43 remains to be determined. C1 [Mahdi, Yassin; Fradejas, Noelia; Guenter, Paul; Braun, Doreen; Schweizer, Ulrich] Univ Bonn, Inst Biochem & Mol Biol, Bonn, Germany. [Xu, Xue-Ming; Carlson, Bradley A.; Southon, Eileen; Tessarollo, Lino; Hatfield, Dolph L.] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schweizer, U (reprint author), Univ Bonn, Inst Biochem & Mol Biol, Bonn, Germany. EM uschweiz@uni-bonn.de OI Schweizer, Ulrich/0000-0003-1380-4780 FU Deutsche Forschungsgemeinschaft (DFG) [Schw914/2-1US]; Intramural Research Program National Cancer Institute, DLH FX This work was supported by Deutsche Forschungsgemeinschaft (DFG), www.dfg.de Schw914/2-1US; Intramural Research Program National Cancer Institute, DLH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 2 Z9 2 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 JUN 4 PY 2015 VL 10 IS 6 AR UNSP e0127349 DI 10.1371/journal.pone.0127349 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ7TC UT WOS:000355701600012 PM 26043259 ER PT J AU Rehm, HL Berg, JS Brooks, LD Bustamante, CD Evans, JP Landrum, MJ Ledbetter, DH Maglott, DR Martin, CL Nussbaum, RL Plon, SE Ramos, EM Sherry, ST Watson, MS AF Rehm, Heidi L. Berg, Jonathan S. Brooks, Lisa D. Bustamante, Carlos D. Evans, James P. Landrum, Melissa J. Ledbetter, David H. Maglott, Donna R. Martin, Christa Lese Nussbaum, Robert L. Plon, Sharon E. Ramos, Erin M. Sherry, Stephen T. Watson, Michael S. CA ClinGen TI ClinGen - The Clinical Genome Resource SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AMERICAN-COLLEGE; GENETIC-VARIANTS; MEDICAL GENETICS; ASSOCIATION; GUIDELINES; STANDARDS; PHENOTYPE AB On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient's family pursues genetic testing that shows a "likely pathogenic" variant for the condition on the basis of a study in an original research publication. Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are tested for the genetic variant to determine their risk. Several family members test negative and are told that they are not at risk for hypertrophic cardiomyopathy and sudden cardiac death, and those who test positive are told that they need to be regularly monitored for cardiomyopathy on echocardiography. Five years later, during a routine clinic visit of one of the genotype-positive family members, the cardiologist queries a database for current knowledge on the genetic variant and discovers that the variant is now interpreted as "likely benign" by another laboratory that uses more recently derived population-frequency data. A newly available testing panel for additional genes that are implicated in hypertrophic cardiomyopathy is initiated on an affected family member, and a different variant is found that is determined to be pathogenic. Family members are retested, and one member who previously tested negative is now found to be positive for this new variant. An immediate clinical workup detects evidence of cardiomyopathy, and an intracardiac defibrillator is implanted to reduce the risk of sudden cardiac death. C1 [Rehm, Heidi L.] Harvard Univ, Sch Med, Boston, MA USA. [Rehm, Heidi L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rehm, Heidi L.] Partners HealthCare, Boston, MA USA. [Berg, Jonathan S.; Evans, James P.] Univ N Carolina, Chapel Hill, NC USA. [Brooks, Lisa D.; Ramos, Erin M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Landrum, Melissa J.; Maglott, Donna R.; Sherry, Stephen T.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Watson, Michael S.] Amer Coll Med Genet & Genom, Bethesda, MD USA. [Bustamante, Carlos D.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ledbetter, David H.; Martin, Christa Lese] Geisinger Hlth Syst, Danville, PA USA. [Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA. RP Rehm, HL (reprint author), Partners HealthCare Personalized Med, Mol Med Lab, 65 Landsdowne St, Cambridge, MA 02139 USA. EM hrehm@partners.org OI Irving, Stephanie/0000-0001-7437-6797; Coughlin II, Curtis/0000-0002-3545-7903; Strande, Natasha/0000-0001-5148-9772; Overby, Casey/0000-0001-9302-5968; Lebo, Matthew/0000-0002-9733-5207; Berg, Jonathan/0000-0003-2360-2664 FU National Human Genome Research Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute [U41 HG006834, U01 HG007436, U01 HG007437, HHSN261200800001E]; Intramural Research Program of the NIH, National Library of Medicine FX ClinGen is funded by the National Human Genome Research Institute, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute (U41 HG006834, U01 HG007436, U01 HG007437, HHSN261200800001E). ClinVar is supported by the Intramural Research Program of the NIH, National Library of Medicine. NR 25 TC 104 Z9 107 U1 6 U2 15 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 JUN 4 PY 2015 VL 372 IS 23 BP 2235 EP 2242 DI 10.1056/NEJMsr1406261 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CK1GK UT WOS:000355955100013 PM 26014595 ER PT J AU Prescott, J DeBuysscher, BL Feldmann, F Gardner, DJ Haddock, E Martellaro, C Scott, D Feldmann, H AF Prescott, Joseph DeBuysscher, Blair L. Feldmann, Friederike Gardner, Donald J. Haddock, Elaine Martellaro, Cynthia Scott, Dana Feldmann, Heinz TI Single-dose live-attenuated vesicular stomatitis virus-based vaccine protects African green monkeys from Nipah virus disease SO VACCINE LA English DT Article DE Nipah virus; Vaccine; Vesicular stomatitis virus; Immune response; Paramyxovirus ID TO-PERSON TRANSMISSION; NONHUMAN-PRIMATES; POSTEXPOSURE PROTECTION; CLINICAL-FEATURES; HEMORRHAGIC-FEVER; MARBURG VIRUSES; SYRIAN-HAMSTER; EBOLA; BANGLADESH; ENCEPHALITIS AB Nipah virus is a zoonotic paramyxovirus that causes severe respiratory and/or encephalitic disease in humans, often resulting in death. It is transmitted from pteropus fruit bats, which serve as the natural reservoir of the virus, and outbreaks occur on an almost annual basis in Bangladesh or India. Outbreaks are small and sporadic, and several cases of human-to-human transmission have been documented as an important feature of the epidemiology of Nipah virus disease. There are no approved countermeasures to combat infection and medical intervention is supportive. We recently generated a recombinant replication-competent vesicular stomatitis virus-based vaccine that encodes a Nipah virus glycoprotein as an antigen and is highly efficacious in the hamster model of Nipah virus disease. Herein, we show that this vaccine protects African green monkeys, a well-characterized model of Nipah virus disease, from disease one month after a single intramuscular administration of the vaccine. Vaccination resulted in a rapid and strong virus-specific immune response which inhibited virus shedding and replication. This vaccine platform provides a rapid means to afford protection from Nipah virus in an outbreak situation. Published by Elsevier Ltd. C1 [Prescott, Joseph; DeBuysscher, Blair L.; Feldmann, Friederike; Gardner, Donald J.; Haddock, Elaine; Martellaro, Cynthia; Scott, Dana; Feldmann, Heinz] NIH, Hamilton, MT 59840 USA. [DeBuysscher, Blair L.] Univ Montana, Missoula, MT 59812 USA. RP Feldmann, H (reprint author), NIH, Hamilton, MT 59840 USA. EM feldmannh@niaid.nih.gov FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The authors would like to thank the Rocky Mountain Veterinary Branch for their care and handling of the animals. We also thank Anita Mora and Austin Athman (Visual Arts, NIAID, NIH) for graphics. This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 34 TC 3 Z9 3 U1 1 U2 14 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 4 PY 2015 VL 33 IS 24 BP 2823 EP 2829 DI 10.1016/j.vaccine.2015.03.089 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA CJ7UO UT WOS:000355705700015 PM 25865472 ER PT J AU Filichia, E Shen, H Zhou, X Qi, X Jin, K Greig, N Hoffer, B Luo, Y AF Filichia, E. Shen, H. Zhou, X. Qi, X. Jin, K. Greig, N. Hoffer, B. Luo, Y. TI FOREBRAIN NEURONAL SPECIFIC ABLATION OF P53 GENE PROVIDES PROTECTION IN A CORTICAL ISCHEMIC STROKE MODEL SO NEUROSCIENCE LA English DT Article DE conditional p53 knockout; stroke; neuroprotection ID FOCAL CEREBRAL-ISCHEMIA; MOUSE-BRAIN; CELL-DEATH; APOPTOSIS; INHIBITOR; MICE; EXPRESSION; MITOCHONDRIA; PROTEIN; DAMAGE AB Cerebral ischemic injury involves death of multiple cell types at the ischemic sites. As a key regulator of cell death, the p53 gene has been implicated in the regulation of cell loss in stroke. Less focal damage is found in stroke animals pre-treated with a p53 inhibitor or in traditional p53 knockout (ko) mice. However, whether the p53 gene plays a direct role in regulating neuronal cell death is unknown. In this study, in contrast to the global inhibition of p53 function by pharmacological inhibitors and in traditional p53 ko mice, we utilized a neuronal specific conditional ko mouse line (CamcreTRP53(loxP/loxP)) to achieve forebrain neuronal specific deletion of p53 and examined the role of the p53 gene in ischemia-induced cell death in neurons. Expression of p53 after stroke is examined using the immunohistochemical method and the outcome of stroke is examined by analysis of infarction size and behavioral deficits caused by stroke. Our data showed that p53 expression is upregulated in the ischemic region in neuronal cells in wildtype (wt) mice but not in CamcreTRP53(loxP/loxP) ko mice. Deletion of the p53 gene in forebrain neurons results in a decreased infarction area in ko mice. Locomotor behavior, measured in automated activity chambers, showed that CamcreTRP53 loxP/loxP ko mice have less locomotor deficits compared to wt mice after middle cerebral artery occlusion (MCAo). We conclude that manipulation of p53 expression in neurons may lead to unique therapeutic development in stroke. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Filichia, E.; Zhou, X.; Jin, K.; Hoffer, B.; Luo, Y.] Case Western Reserve Univ, Dept Neurol Surg, Cleveland, OH 44106 USA. [Shen, H.] Natl Inst Drug Abuse, Baltimore, MD USA. [Qi, X.] Case Western Reserve Univ, Dept Physiol, Cleveland, OH 44106 USA. [Greig, N.] Natl Inst Aging, Baltimore, MD USA. RP Luo, Y (reprint author), Case Western Reserve Univ, Dept Neurol Surg, 2109 Adelbert Rd, Cleveland, OH 44106 USA. EM yxl710@case.edu RI Qi, Xin/D-1512-2013 OI Qi, Xin/0000-0002-9578-3890 FU American Heart Association National Scientist Development Award; National Institute on Aging, NIH FX Dr. Yu Luo is funded by the American Heart Association National Scientist Development Award. This work is supported in part by the Intramural Research Program of the National Institute on Aging, NIH. NR 51 TC 5 Z9 6 U1 1 U2 4 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 JUN 4 PY 2015 VL 295 BP 1 EP 10 DI 10.1016/j.neuroscience.2015.03.018 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CG3VQ UT WOS:000353208100001 PM 25779964 ER PT J AU Zimmer, ER Torrez, VR Kalinine, E Augustin, MC Zenki, KC Almeida, RF Hansel, G Muller, AP Souza, DO Machado-Vieira, R Portela, LV AF Zimmer, Eduardo R. Torrez, Vitor R. Kalinine, Eduardo Augustin, Marina C. Zenki, Kamila C. Almeida, Roberto F. Hansel, Gisele Muller, Alexandre P. Souza, Diogo O. Machado-Vieira, Rodrigo Portela, Luis V. TI Long-term NMDAR antagonism correlates reduced astrocytic glutamate uptake with anxiety-like phenotype SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE anxiety; astrocytes; behavior; glutamate; memantine ID RAT-BRAIN; MEMANTINE; MODELS; TRANSPORTER; DISORDERS; BEHAVIORS; BLOCKADE; MEMORY; MICE AB The role of glutamate N-methyl-D-aspartate receptor (NMDAR) hypofunction has been extensively studied in schizophrenia; however, less is known about its role in anxiety disorders. Recently, it was demonstrated that astrocytic GLT-1 blockade leads to an anxiety-like phenotype. Although astrocytes are capable of modulating NMDAR activity through glutamate uptake transporters, the relationship between astrocytic glutamate uptake and the development of an anxiety phenotype remains poorly explored. Here, we aimed to investigative whether long-term antagonism of NMDAR impacts anxiety-related behaviors and astrocytic glutamate uptake. Memantine, an NMDAR antagonist, was administered daily for 24 days to healthy adult CF-1 mice by oral gavage at doses of 5, 10, or 20 mg/kg. The mice were submitted to a sequential battery of behavioral tests (open field, light dark box and elevated plus-maze tests). We then evaluated glutamate uptake activity and the immunocontents of glutamate transporters in the frontoparietal cortex and hippocampus. Our results demonstrated that long-term administration of memantine induces anxiety-like behavior in mice in the light dark box and elevated plus-maze paradigms. Additionally, the administration of memantine decreased glutamate uptake activity in both the frontoparietal cortex and hippocampus without altering the immunocontent of either GLT-1 or GLAST. Remarkably, the memantine-induced reduction in glutamate uptake was correlated with enhancement of an anxiety-like phenotype. In conclusion, long-term NMDAR antagonism with memantine induces anxiety-like behavior that is associated with reduced glutamate uptake activity but that is not dependent on GLT-1 or GLAST protein expression. Our study suggests that NMDAR and glutamate uptake hypofunction may contribute to the development of conditions that fall within the category of anxiety disorders. C1 [Zimmer, Eduardo R.; Torrez, Vitor R.; Kalinine, Eduardo; Augustin, Marina C.; Zenki, Kamila C.; Almeida, Roberto F.; Hansel, Gisele; Muller, Alexandre P.; Souza, Diogo O.; Portela, Luis V.] Univ Fed Rio Grande do Sul, Dept Biochem, BR-90035003 Porto Alegre, RS, Brazil. [Kalinine, Eduardo] Univ Fed Sergipe, Dept Physiol, Sao Cristovao, Brazil. [Muller, Alexandre P.] Univ Extremo Sul Catarinense, Lab Exercise Biochem & Physiol, Criciuma, Brazil. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Neurosci Lab, Inst & Dept Psychiat, LIM 27, Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. RP Portela, LV (reprint author), Univ Fed Rio Grande do Sul, Dept Biochem, 2600 Ramiro Barcelos St, BR-90035003 Porto Alegre, RS, Brazil. EM roskaportela@gmail.com RI Torrez, Vitor/F-6045-2016; MACHADO-VIEIRA, RODRIGO/D-8293-2012; Zimmer, Eduardo/I-2932-2015 OI Torrez, Vitor/0000-0003-2471-0165; MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Zimmer, Eduardo/0000-0002-5349-0053 FU Brazilian agency National Counsel of Technological and Scientific Development (CNPq); Brazilian agency CAPES; Brazilian agency FAPERGS; Brazilian agency Brazilian Institute of Neuroscience (IBNnet); Brazilian agency FINEP; Brazilian agency National Institute of Science and Technology (INCT) Excitotoxicity and Neuroprotection FX This work was supported by the following Brazilian agencies and grants: National Counsel of Technological and Scientific Development (CNPq), CAPES, FAPERGS, Brazilian Institute of Neuroscience (IBNnet), FINEP, and National Institute of Science and Technology (INCT) Excitotoxicity and Neuroprotection. NR 39 TC 8 Z9 9 U1 1 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD JUN 3 PY 2015 VL 9 AR 219 DI 10.3339/fnce1.2015.00219 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CM3VG UT WOS:000357612500001 PM 26089779 ER PT J AU Cheng, JJ Giguere, PM Lv, W Roth, BL Kozikowski, AP AF Cheng, Jianjun Giguere, Patrick M. Lv, Wei Roth, Bryan L. Kozikowski, Alan P. TI Design and synthesis of (2-(5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)cyclopropyl)methana mine as a selective serotonin 2C agonist SO TETRAHEDRON LETTERS LA English DT Article DE Serotonin 2C; Agonist; Benzofuran; Cyclopropylmethanamine ID RECEPTOR ANTAGONIST; LY277359 MALEATE; ZATOSETRON; POTENT; DRUGS AB A conformationally restricted analog of a selective cyclopropane-bearing serotonin 2C agonist was designed and synthesized. A 2,2-dimethyl-2,3-dihydrobenzofuran scaffold was investigated as a constrained variant of a biologically active isopropyl phenyl ether. Construction of the required dimethyl2,3-dihydrobenzofuran intermediate began using a procedure that relied on a microwave-assisted alkylation reaction. The synthesis of the designed compound as its HCl salt is reported in a total of 12 steps and 17% overall yield. Biological evaluation revealed the constrained analog to be a selective serotonin 2C agonist with modest potency. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Cheng, Jianjun; Lv, Wei; Kozikowski, Alan P.] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. [Giguere, Patrick M.; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Natl Inst Mental Hlth, Psychoact Drug Screening Program,Chapel Hill Med, Chapel Hill, NC 27599 USA. [Giguere, Patrick M.; Roth, Bryan L.] Univ N Carolina, Div Chem Biol & Med Chem, Chapel Hill Med Sch, Chapel Hill, NC 27599 USA. RP Kozikowski, AP (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, 833 South Wood St, Chicago, IL 60612 USA. EM kozikowa@uic.edu RI Roth, Bryan/F-3928-2010; OI Cheng, Jianjun/0000-0001-6065-2682 FU NIMH NIH HHS [R01 MH099993] NR 18 TC 3 Z9 3 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUN 3 PY 2015 VL 56 IS 23 BP 3420 EP 3422 DI 10.1016/j.tetlet.2015.01.060 PG 3 WC Chemistry, Organic SC Chemistry GA CK9FA UT WOS:000356544800112 PM 26120215 ER PT J AU Zheng, XH Perera, L Mueller, GA DeRose, EF London, RE AF Zheng, Xunhai Perera, Lalith Mueller, Geoffrey A. DeRose, Eugene F. London, Robert E. TI Asymmetric conformational maturation of HIV-1 reverse transcriptase SO ELIFE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DYNAMICS IN-VIVO; RNASE-H DOMAIN; P66/P51 HETERODIMER; EFAVIRENZ BINDING; TEMPLATE-PRIMER; P51 SUBUNIT; INHIBITORS; NMR; POLYMERIZATION AB HIV-1 reverse transcriptase utilizes a metamorphic polymerase domain that is able to adopt two alternate structures that fulfill catalytic and structural roles, thereby minimizing its coding requirements. This ambiguity introduces folding challenges that are met by a complex maturation process. We have investigated this conformational maturation using NMR studies of methyl-labeled RT for the slower processes in combination with molecular dynamics simulations for rapid processes. Starting from an inactive conformation, the p66 precursor undergoes a unimolecular isomerization to a structure similar to its active form, exposing a large hydrophobic surface that facilitates initial homodimer formation. The resulting p66/p66' homodimer exists as a conformational heterodimer, after which a series of conformational adjustments on different time scales can be observed. Formation of the inter-subunit RH:thumb' interface occurs at an early stage, while maturation of the connection' and unfolding of the RH' domains are linked and occur on a much slower time scale. C1 [Zheng, Xunhai; Perera, Lalith; Mueller, Geoffrey A.; DeRose, Eugene F.; London, Robert E.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov FU National Institute of Environmental Health Sciences (NIEHS) [Z01-ES050147, HHSN273200700046U] FX National Institute of Environmental Health Sciences (NIEHS) Z01-ES050147 Robert E London; National Institute of Environmental Health Sciences (NIEHS) HHSN273200700046U Eugene F DeRose NR 33 TC 3 Z9 3 U1 2 U2 8 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD JUN 3 PY 2015 VL 4 AR e06359 DI 10.7554/eLife.06359 PG 24 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CK3VI UT WOS:000356144000001 ER PT J AU Massa, C Thomas, C Wang, E Marincola, F Seliger, B AF Massa, Chiara Thomas, Carolin Wang, Ena Marincola, Francesco Seliger, Barbara TI Different maturation cocktails provide dendritic cells with different chemoattractive properties SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE DC; Vaccination; Chemokines; Human; Innate immunity; T cells ID REGULATORY T-CELLS; NATURAL-KILLER; CHEMOKINE RECEPTORS; PROSTAGLANDIN E-2; MELANOMA PATIENTS; CANCER-PATIENTS; EXPRESSION; MIGRATION; INDUCE; LYMPHOCYTES AB Background: Dendritic cells (DC) are currently implemented as immunotherapeutic strategy for the treatment of tumor patients based on their central role in the immune system. Despite good results were obtained in vitro and in animal models, their clinical use has provided limited success suggesting the requirement to optimise the protocol for their production. Methods: A cDNA array was performed on FastDC obtained from the differentiation of human peripheral blood monocytes stimulated with the clinical gold standard or with two alternative maturation cocktails combining interferon (IFN)gamma and ligands for different toll like receptors (TLR). Results: A stronger modulation of the DC transcriptome with respect to immature DC was found in alternatively stimulated DC when compared to DC stimulated with the clinical gold standard. A major class of molecules differentially expressed using distinct DC stimulation protocols were chemokines. Validation of their differential expression pattern at the mRNA and protein level confirmed the secretion of inflammatory chemokines by the alternative DC. Functional analyses of the chemotactic properties of DC "wash out" supernatants highlighted the ability of alternative, but not of gold standard DC to efficiently recruit immune cells with a prevalence of monocytes. Effector cells belonging to the innate as well as adaptive immunity were also attracted and the interaction with alternative DC resulted in enhanced secretion of IFN gamma and induction of cytotoxic activity. Using leukocytes from cancer patients, it was demonstrated that the monocyte-attracting activity targeted cells with an inflammatory phenotype characterised by high levels of HLA-DR expression. Conclusions: Despite other classes of immune modulatory genes differently expressed in the alternative DC require to be investigated and characterised regarding their functional consequences, the reduced maturation state and chemoattractive properties of the gold standard versus alternative DC clearly promote the necessity to change the clinically used maturation cocktail of DC in order to improve the outcome of patients treated with DC-based vaccines. C1 [Massa, Chiara; Thomas, Carolin; Seliger, Barbara] Univ Halle Wittenberg, Inst Med Immunol, D-06112 Halle, Germany. [Wang, Ena; Marincola, Francesco] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco] Sidra Med & Res Ctr, Doha, Qatar. RP Seliger, B (reprint author), Univ Halle Wittenberg, Inst Med Immunol, Magdeburger Str 2, D-06112 Halle, Germany. EM barbara.seliger@uk-halle.de FU Mildred Scheel Foundation [111105] FX This work was supported from the Mildred Scheel Foundation (111105, to CM and BS). NR 58 TC 3 Z9 3 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 3 PY 2015 VL 13 AR 175 DI 10.1186/s12967-015-0528-7 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CK3VG UT WOS:000356143700001 PM 26695182 ER PT J AU Arem, H Yu, K Xiong, XQ Moy, K Freedman, ND Mayne, ST Albanes, D Amundadottir, LT Arslan, AA Austin, M Bamlet, WR Beane-Freeman, L Bracci, P Canzian, F Chanock, SJ Cotterchio, M Duell, EJ Gallinger, S Giles, GG Goggins, M Goodman, PJ Hartge, P Hassan, M Helzlsouer, K Henderson, B Holly, EA Hoover, R Jacobs, EJ Kamineni, A Klein, A Klein, E Kolonel, LN Li, DH Malats, N Mannisto, S McCullough, ML Olson, SH Orlow, I Peters, U Petersen, GM Porta, M Severi, G Shu, XO Van den Eeden, S Visvanathan, K White, E Yu, H Zeleniuch-Jacquotte, A Zheng, W Tobias, GS Maeder, D Brotzman, M Risch, H Sampson, JN Stolzenberg-Solomon, RZ AF Arem, Hannah Yu, Kai Xiong, Xiaoqin Moy, Kristin Freedman, Neal D. Mayne, Susan T. Albanes, Demetrius Amundadottir, Laufey T. Arslan, Alan A. Austin, Melissa Bamlet, William R. Beane-Freeman, Laura Bracci, Paige Canzian, Federico Chanock, Stephen J. Cotterchio, Michelle Duell, Eric J. Gallinger, Steve Giles, Graham G. Goggins, Michael Goodman, Phyllis J. Hartge, Patricia Hassan, Manal Helzlsouer, Kathy Henderson, Brian Holly, Elizabeth A. Hoover, Robert Jacobs, Eric J. Kamineni, Aruna Klein, Alison Klein, Eric Kolonel, Laurence N. Li, Donghui Malats, Nria Maennistoe, Satu McCullough, Marjorie L. Olson, Sara H. Orlow, Irene Peters, Ulrike Petersen, Gloria M. Porta, Miquel Severi, Gianluca Shu, Xiao-Ou Van den Eeden, Stephen Visvanathan, Kala White, Emily Yu, Herbert Zeleniuch-Jacquotte, Anne Zheng, Wei Tobias, Geoffrey S. Maeder, Dennis Brotzman, Michelle Risch, Harvey Sampson, Joshua N. Stolzenberg-Solomon, Rachael Z. TI Vitamin D Metabolic Pathway Genes and Pancreatic Cancer Risk (vol 10, e0117574, 2015) SO PLOS ONE LA English DT Correction C1 [Amundadottir, Laufey T.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Van den Eeden, Stephen] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Van den Eeden, Stephen] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. RI Malats, Nuria/H-7041-2015; Porta, Miquel/B-5787-2008; Freedman, Neal/B-9741-2015; Tobias, Geoffrey/M-4135-2016; Beane Freeman, Laura/C-4468-2015 OI Malats, Nuria/0000-0003-2538-3784; Porta, Miquel/0000-0003-1684-7428; Freedman, Neal/0000-0003-0074-1098; Tobias, Geoffrey/0000-0002-2878-8253; Beane Freeman, Laura/0000-0003-1294-4124 NR 1 TC 0 Z9 0 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 JUN 3 PY 2015 VL 10 IS 6 AR e0129983 DI 10.1371/journal.pone.0129983 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ7ST UT WOS:000355700700152 PM 26039095 ER PT J AU Dworzak, J Renvoise, B Habchi, J Yates, EV Combadiere, C Knowles, TP Dobson, CM Blackstone, C Paulsen, O Murphy, PM AF Dworzak, Jenny Renvoise, Benoit Habchi, Johnny Yates, Emma V. Combadiere, Christophe Knowles, Tuomas P. Dobson, Christopher M. Blackstone, Craig Paulsen, Ole Murphy, Philip M. TI Neuronal Cx3cr1 Deficiency Protects against Amyloid beta-Induced Neurotoxicity SO PLOS ONE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; RAT HIPPOCAMPAL-NEURONS; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; A-BETA; GLUTAMATERGIC SYNAPSES; MICROGLIAL ACTIVATION; FRACTALKINE RECEPTOR; SYNAPTIC PLASTICITY; CHEMOKINE RECEPTORS AB Cx3cr1, the receptor for the chemokine Cx3cl1 (fractalkine), has been implicated in the progression and severity of Alzheimer's disease-like pathology in mice, but the underlying mechanisms remain unclear. A complicating factor is that Cx3cr1 has been demonstrated in both neurons and microglia. Here, we have dissected the differences between neuronal and microglial Cx3cr1, specifically by comparing direct amyloid-beta-induced toxicity in cultured, mature, microglia-depleted hippocampal neurons from wild-type and Cx3cr1(-/-) mice. Wild-type neurons expressed both Cx3cl1 and Cx3cr1 and released Cx3cl1 in response to amyloid-beta. Knockout of neuronal Cx3cr1 abated amyloid-beta-induced lactate dehydrogenase release. Furthermore, amyloid-beta differentially induced depression of pre- and postsynaptic components of miniature excitatory postsynaptic currents, in a peptide conformation-dependent manner. Knockout of neuronal Cx3cr1 abated effects of both amyloid-beta conformational states, which were differentiable by aggregation kinetics and peptide morphology. We obtained similar results after both acute and chronic treatment of cultured neurons with the Cx3cr1 antagonist F1. Thus, neuronal Cx3cr1 may impact Alzheimer's disease-like pathology by modulating conformational state-dependent amyloid-beta-induced synaptotoxicity. C1 [Dworzak, Jenny; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Dworzak, Jenny; Paulsen, Ole] Univ Cambridge, Dept Physiol Dev & Neurosci, Neuronal Oscillat Grp, Cambridge, England. [Dworzak, Jenny; Renvoise, Benoit; Blackstone, Craig] NINDS, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Habchi, Johnny; Yates, Emma V.; Knowles, Tuomas P.; Dobson, Christopher M.; Murphy, Philip M.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Combadiere, Christophe] INSERM, Ctr Immunol & Malad Infect Paris, Paris, France. RP Paulsen, O (reprint author), Univ Cambridge, Dept Physiol Dev & Neurosci, Neuronal Oscillat Grp, Cambridge, England. EM op210@cam.ac.uk; pmm@nih.gov RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 FU Division of Intramural Research, NIAID; NINDS, NIH; Alzheimer's Research UK [ARUK-PPG2012B-12]; NIH-Oxford-Cambridge Biomedical Scholars fellowship; Medical Scientist Training Program of Icahn School of Medicine at Mount Sinai FX This work was supported by the Division of Intramural Research, NIAID and NINDS, NIH and Alzheimer's Research UK (ARUK-PPG2012B-12). JD is a MD/PhD biomedical scholar supported by the NIH-Oxford-Cambridge Biomedical Scholars fellowship and Medical Scientist Training Program of Icahn School of Medicine at Mount Sinai. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 4 Z9 4 U1 1 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 3 PY 2015 VL 10 IS 6 AR e0127730 DI 10.1371/journal.pone.0127730 PG 25 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ7ST UT WOS:000355700700072 PM 26038823 ER PT J AU Lindner, MD Nakamura, RK AF Lindner, Mark D. Nakamura, Richard K. TI Examining the Predictive Validity of NIH Peer Review Scores SO PLOS ONE LA English DT Review ID CARDIOVASCULAR R01 GRANTS; CITATION BIAS; GENETIC ASSOCIATION; CLINICAL-TRIALS; STATISTICAL-ANALYSIS; PERCENTILE RANKING; FACULTY SALARIES; COMPLEX DISEASES; PUBLICATION BIAS; MEDICAL-RESEARCH AB The predictive validity of peer review at the National Institutes of Health (NIH) has not yet been demonstrated empirically. It might be assumed that the most efficient and expedient test of the predictive validity of NIH peer review would be an examination of the correlation between percentile scores from peer review and bibliometric indices of the publications produced from funded projects. The present study used a large dataset to examine the rationale for such a study, to determine if it would satisfy the requirements for a test of predictive validity. The results show significant restriction of range in the applications selected for funding. Furthermore, those few applications that are funded with slightly worse peer review scores are not selected at random or representative of other applications in the same range. The funding institutes also negotiate with applicants to address issues identified during peer review. Therefore, the peer review scores assigned to the submitted applications, especially for those few funded applications with slightly worse peer review scores, do not reflect the changed and improved projects that are eventually funded. In addition, citation metrics by themselves are not valid or appropriate measures of scientific impact. The use of bibliometric indices on their own to measure scientific impact would likely increase the inefficiencies and problems with replicability already largely attributed to the current over-emphasis on bibliometric indices. Therefore, retrospective analyses of the correlation between percentile scores from peer review and bibliometric indices of the publications resulting from funded grant applications are not valid tests of the predictive validity of peer review at the NIH. C1 [Lindner, Mark D.; Nakamura, Richard K.] NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Lindner, MD (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM Mark.Lindner@nih.gov NR 108 TC 3 Z9 3 U1 2 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 JUN 3 PY 2015 VL 10 IS 6 AR UNSP e0126938 DI 10.1371/journal.pone.0126938 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ7ST UT WOS:000355700700045 PM 26039440 ER PT J AU Pendrak, ML Roberts, DD AF Pendrak, Michael L. Roberts, David D. TI Hbr1 Activates and Represses Hyphal Growth in Candida albicans and Regulates Fungal Morphogenesis under Embedded Conditions SO PLOS ONE LA English DT Article ID INVASIVE FILAMENTOUS GROWTH; TRANSCRIPTION FACTOR; GENE DISRUPTION; PESCADILLO HOMOLOG; ADENYLYL-CYCLASE; IN-VIVO; YEAST; VIRULENCE; PROTEINS; FARNESOL AB Transitions between yeast and hyphae are essential for Candida albicans pathogenesis. The genetic programs that regulate its hyphal development can be distinguished by embedded versus aerobic surface agar invasion. Hbr1, a regulator of white-opaque switching, is also a positive and negative regulator of hyphal invasion. During embedded growth at 24 degrees C, an HBR1/hbr1 strain formed constitutively filamentous colonies throughout the matrix, resembling EFG1 null colonies, and a subset of long unbranched hyphal aggregates enclosed in a spindle-shaped capsule. Inhibition of adenylate cyclase with farnesol perturbed the filamentation of HBR1/hbr1 cells producing cytokinesis-defective hyphae whereas farnesol treated EFG1 null cells produced abundant opaque-like cells. Point mutations in the Hbr1 ATP-binding domain caused distinct filamentation phenotypes including uniform radial hyphae, hyphal sprouts, and massive yeast cell production. Conversely, aerobic surface colonies of the HBR1 heterozygote on Spider and GlcNAc media lacked filamentation that could be rescued by growth under low (5%) O-2. Consistent with these morphogenesis defects, the HBR1 heterozygote exhibited attenuated virulence in a mouse candidemia model. These data define Hbr1 as an ATP-dependent positive and negative regulator of hyphal development that is sensitive to hypoxia. C1 [Pendrak, Michael L.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pendrak, ML (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 2A33, Bethesda, MD 20892 USA. EM pendrakm@mail.nih.gov; droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 65 TC 0 Z9 0 U1 0 U2 2 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 3 PY 2015 VL 10 IS 6 AR UNSP e0126919 DI 10.1371/journal.pone.0126919 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ7ST UT WOS:000355700700043 PM 26039220 ER PT J AU Thanos, PK Michaelides, M Subrize, M Miller, ML Bellezza, R Cooney, RN Leggio, L Wang, GJ Rogers, AM Volkow, ND Hajnal, A AF Thanos, Panayotis K. Michaelides, Mike Subrize, Mike Miller, Mike L. Bellezza, Robert Cooney, Robert N. Leggio, Lorenzo Wang, Gene-Jack Rogers, Ann M. Volkow, Nora D. Hajnal, Andras TI Roux-en-Y Gastric Bypass Alters Brain Activity in Regions that Underlie Reward and Taste Perception SO PLOS ONE LA English DT Article ID CONDITIONED PLACE PREFERENCE; VERTICAL BANDED GASTROPLASTY; BINGE-EATING DISORDER; WEIGHT-LOSS SURGERY; INDUCED OBESE RATS; TERM FOLLOW-UP; BARIATRIC SURGERY; NUCLEUS-ACCUMBENS; SWEET TASTE; DOPAMINE-D4 RECEPTORS AB Background Roux-en-Y gastric bypass (RYGB) surgery is a very effective bariatric procedure to achieve significant and sustained weight loss, yet little is known about the procedure's impact on the brain. This study examined the effects of RYGB on the brain's response to the anticipation of highly palatable versus regular food. Methods High fat diet-induced obese rats underwent RYGB or sham operation and were then tested for conditioned place preference (CPP) for the bacon-paired chamber, relative to the chow-paired chamber. After CPP, animals were placed in either chamber without the food stimulus, and brain-glucose metabolism (BGluM) was measured using positron emission tomography (mu PET). Results Bacon CPP was only observed in RYGB rats that had stable weight loss following surgery. BGluM assessment revealed that RYGB selectively activated regions of the right and midline cerebellum (Lob 8) involved in subjective processes related to reward or expectation. Also, bacon anticipation led to significant activation in the medial parabrachial nuclei (important in gustatory processing) and dorsomedial tegmental area (key to reward, motivation, cognition and addiction) in RYGB rats; and activation in the retrosplenial cortex (default mode network), and the primary visual cortex in control rats. Conclusions RYGB alters brain activity in areas involved in reward expectation and sensory (taste) processing when anticipating a palatable fatty food. Thus, RYGB may lead to changes in brain activity in regions that process reward and taste-related behaviors. Specific cerebellar regions with altered metabolism following RYGB may help identify novel therapeutic targets for treatment of obesity. C1 [Thanos, Panayotis K.; Subrize, Mike; Bellezza, Robert] SUNY Stony Brook, Dept Psychol, Behav Neuropharmacol & Neuroimaging Lab, Stony Brook, NY 11794 USA. [Michaelides, Mike; Miller, Mike L.] Mt Sinai Med Ctr, Dept Neurosci, New York, NY USA. [Cooney, Robert N.] SUNY Upstate Med Univ, Dept Surg, Syracuse, NY 13210 USA. [Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Leggio, Lorenzo] Brown Univ, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Providence, RI 02912 USA. [Wang, Gene-Jack; Volkow, Nora D.] NIAAA, Intramural Res Program, NIH, Bethesda, MD USA. [Hajnal, Andras] Penn State Univ, Dept Neural & Behav Sci, Hershey, PA USA. [Rogers, Ann M.; Hajnal, Andras] Penn State Univ, Dept Surg, Hershey, PA USA. RP Thanos, PK (reprint author), SUNY Stony Brook, Dept Psychol, Behav Neuropharmacol & Neuroimaging Lab, Stony Brook, NY 11794 USA. EM peter.thanos@stonybrook.edu RI Leggio, Lorenzo/M-2972-2016; OI Miller, Michael/0000-0002-6350-5706 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK080899]; National Institute on Alcohol Abuse and Alcoholism [AA 11034] FX National Institute of Diabetes and Digestive and Kidney Diseases (DK080899) and National Institute on Alcohol Abuse and Alcoholism (AA 11034). NR 100 TC 3 Z9 3 U1 1 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 JUN 3 PY 2015 VL 10 IS 6 AR UNSP e0125570 DI 10.1371/journal.pone.0125570 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ7ST UT WOS:000355700700009 PM 26039080 ER PT J AU Song, XR Wang, XY Yu, SX Cao, JB Li, SH Li, J Liu, G Yang, HH Chen, XY AF Song, Xiao-Rong Wang, Xiaoyong Yu, Shu-Xian Cao, Jianbo Li, Shi-Hua Li, Juan Liu, Gang Yang, Huang-Hao Chen, Xiaoyuan TI Co9Se8 Nanoplates as a New Theranostic Platform for Photoacoustic/Magnetic Resonance Dual-Modal-Imaging-Guided Chemo-Photothermal Combination Therapy SO ADVANCED MATERIALS LA English DT Article DE chemotherapy; magnetic resonance imaging; nanoplates; photoacoustic imaging; photothermal therapy ID IN-VIVO; DRUG-DELIVERY; BIOMEDICAL APPLICATIONS; COBALT NANOPARTICLES; CARBON NANOTUBES; CANCER-CELLS; MAGNETIC NANOPARTICLES; MESOPOROUS SILICA; CONTRAST AGENTS; MRI CONTRAST C1 [Song, Xiao-Rong; Yu, Shu-Xian; Li, Shi-Hua; Li, Juan; Yang, Huang-Hao] Fuzhou Univ, Coll Chem, Key Lab Anal & Detect Technol Food Safety, MOE,State Key Lab Photocatalysis Energy & Environ, Fuzhou 350108, Peoples R China. [Wang, Xiaoyong; Cao, Jianbo; Liu, Gang] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361005, Peoples R China. [Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. RP Liu, G (reprint author), Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361005, Peoples R China. EM gangliu.cmitm@xmu.edu.cn; hhyang@fio.org.cn FU National Basic Research Program of China [2010CB732403, 2014CB744503]; National Natural Science Foundation of China [21125524, 21475026, 81422023, 51273165]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1116]; National Science Foundation of Fujian Province [2010J06003]; Program for New Century Excellent Talents in University [NCET-13-0502]; Fundamental Research Funds for the Central Universities [2013121039] FX X.R.S. and X.Y.W. contributed equally to this work. The authors gratefully acknowledge the financial support from the National Basic Research Program of China (No. 2010CB732403, 2014CB744503), the National Natural Science Foundation of China (No. 21125524, 21475026, 81422023, 51273165), the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1116), the National Science Foundation of Fujian Province (No. 2010J06003), Program for New Century Excellent Talents in University (NCET-13-0502), and Fundamental Research Funds for the Central Universities (2013121039). NR 86 TC 56 Z9 56 U1 49 U2 170 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0935-9648 EI 1521-4095 J9 ADV MATER JI Adv. Mater. PD JUN 3 PY 2015 VL 27 IS 21 BP 3285 EP 3291 DI 10.1002/adma.201405634 PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CJ7CA UT WOS:000355650300008 PM 25885638 ER PT J AU Pignatelli, M Bonci, A AF Pignatelli, Marco Bonci, Antonello TI Role of Dopamine Neurons in Reward and Aversion: A Synaptic Plasticity Perspective SO NEURON LA English DT Review ID VENTRAL TEGMENTAL AREA; LONG-TERM DEPRESSION; METABOTROPIC GLUTAMATE RECEPTORS; NUCLEUS-ACCUMBENS; AMPA RECEPTOR; PREFRONTAL CORTEX; NMDA RECEPTORS; FIRING PATTERN; IN-VIVO; SUBSYNAPTIC DISTRIBUTION AB The brain is wired to predict future outcomes. Experience-dependent plasticity at excitatory synapses within dopamine neurons of the ventral tegmental area, a key region for a broad range of motivated behaviors, is thought to be a fundamental cellular mechanism that enables adaptation to a dynamic environment. Thus, depending on the circumstances, dopamine neurons are capable of processing both positive and negative reinforcement learning strategies. In this review, we will discuss how changes in synaptic plasticity of dopamine neurons may affect dopamine release, as well as behavioral adaptations to different environmental conditions falling at opposite ends of a saliency spectrum ranging from reward to aversion. C1 [Pignatelli, Marco; Bonci, Antonello] NIDA, Intramural Res Program, Synapt Plast Sect, Baltimore, MD 21224 USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, MD 21205 USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. RP Bonci, A (reprint author), NIDA, Intramural Res Program, Synapt Plast Sect, Baltimore, MD 21224 USA. EM antonello.bonci@nih.gov NR 125 TC 28 Z9 29 U1 7 U2 47 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD JUN 3 PY 2015 VL 86 IS 5 BP 1145 EP 1157 DI 10.1016/j.neuron.2015.04.015 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CJ7HV UT WOS:000355666400006 PM 26050034 ER PT J AU Johansen, LM DeWald, LE Shoemaker, CJ Hoffstrom, BG Lear-Rooney, CM Stossel, A Nelson, E Delos, SE Simmons, JA Grenier, JM Pierce, LT Pajouhesh, H Lehar, J Hensley, LE Glass, PJ White, JM Olinger, GG AF Johansen, Lisa M. DeWald, Lisa Evans Shoemaker, Charles J. Hoffstrom, Benjamin G. Lear-Rooney, Calli M. Stossel, Andrea Nelson, Elizabeth Delos, Sue E. Simmons, James A. Grenier, Jill M. Pierce, Laura T. Pajouhesh, Hassan Lehar, Joseph Hensley, Lisa E. Glass, Pamela J. White, Judith M. Olinger, Gene G. TI A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID NIEMANN-PICK C1; CELL ENTRY; HEMORRHAGIC-FEVER; FILOVIRUS ENTRY; MOUSE MODEL; GLYCOPROTEIN; INFECTION; BINDING; FUSION; ACID AB Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested similar to 2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections. C1 [Johansen, Lisa M.; Hoffstrom, Benjamin G.; Grenier, Jill M.; Pierce, Laura T.; Pajouhesh, Hassan; Lehar, Joseph] Horizon Discovery Inc, Cambridge, MA 02142 USA. [DeWald, Lisa Evans; Lear-Rooney, Calli M.; Stossel, Andrea; Hensley, Lisa E.; Glass, Pamela J.; Olinger, Gene G.] US Army Med Res Inst Infect Dis, Frederick, MD 21702 USA. [Shoemaker, Charles J.; Nelson, Elizabeth; Delos, Sue E.; Simmons, James A.; White, Judith M.] Univ Virginia, Charlottesville, VA 22908 USA. [Lehar, Joseph] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. RP Olinger, GG (reprint author), NIAID, Integrated Res Facil, Div Clin Res, B-8200 Res Plaza, Frederick, MD 21702 USA. EM gene.olinger@nih.gov FU Defense Threat Reduction Agency project [4.10007_08_RD_B]; USAMRIID [W81XWH-08-0051]; NIH [U54 AI057168]; DTRA [W81XWH-12-P-0007]; National Research Council Research Associateship Award at USAMRIID FX This work is funded by Defense Threat Reduction Agency project 4.10007_08_RD_B awarded to G.G.O. and subcontract (W81XWH-08-0051) awarded to L.M.J. from USAMRIID and an NIH grant U54 AI057168 and DTRA subcontract W81XWH-12-P-0007 awarded to J.M.W. This research was performed while L.E.D. held a National Research Council Research Associateship Award at USAMRIID. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. NR 57 TC 19 Z9 19 U1 7 U2 20 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 JUN 3 PY 2015 VL 7 IS 290 AR 290ra89 DI 10.1126/scitranslmed.aaa5597 PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CJ6WI UT WOS:000355635500007 PM 26041706 ER PT J AU Manolio, TA Abramowicz, M Al-Mulla, F Anderson, W Balling, R Berger, AC Bleyl, S Chakravarti, A Chantratita, W Chisholm, RL Dissanayake, VHW Dunn, M Dzau, VJ Han, BG Hubbard, T Kolbe, A Korf, B Kubo, M Lasko, P Leego, E Mahasirimongkol, S Majumdar, PP Matthijs, G McLeod, HL Metspalu, A Meulien, P Miyano, S Naparstek, Y O'Rourke, PP Patrinos, GP Rehm, HL Relling, MV Rennert, G Rodriguez, LL Roden, DM Shuldiner, AR Sinha, S Tan, P Ulfendahl, M Ward, R Williams, MS Wong, JEL Green, ED Ginsburg, GS AF Manolio, Teri A. Abramowicz, Marc Al-Mulla, Fahd Anderson, Warwick Balling, Rudi Berger, Adam C. Bleyl, Steven Chakravarti, Aravinda Chantratita, Wasun Chisholm, Rex L. Dissanayake, Vajira H. W. Dunn, Michael Dzau, Victor J. Han, Bok-Ghee Hubbard, Tim Kolbe, Anne Korf, Bruce Kubo, Michiaki Lasko, Paul Leego, Erkki Mahasirimongkol, Surakameth Majumdar, Partha P. Matthijs, Gert McLeod, Howard L. Metspalu, Andres Meulien, Pierre Miyano, Satoru Naparstek, Yaakov O'Rourke, P. Pearl Patrinos, George P. Rehm, Heidi L. Relling, Mary V. Rennert, Gad Rodriguez, Laura Lyman Roden, Dan M. Shuldiner, Alan R. Sinha, Sukdeb Tan, Patrick Ulfendahl, Mats Ward, Robyn Williams, Marc S. Wong, John E. L. Green, Eric D. Ginsburg, Geoffrey S. TI Global implementation of genomic medicine: We are not alone SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID ECONOMIC-EVALUATION; PHARMACOGENOMICS; PROJECT; RECONSTRUCTION; OPPORTUNITIES; EPIDEMIOLOGY; CHALLENGES; PHENOTYPE; SINGAPORE; COUNTRIES AB Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual efforts might benefit from the sharing of approaches and lessons learned in other locales. The U.S. National Human Genome Research Institute and the National Academy of Medicine recently brought together 25 of these groups to compare projects, to examine the current state of implementation and desired near-term capabilities, and to identify opportunities for collaboration that promote the responsible practice of genomic medicine. Efforts to coalesce these groups around concrete but compelling signature projects should accelerate the responsible implementation of genomic medicine in efforts to improve clinical care worldwide. C1 [Manolio, Teri A.; Rodriguez, Laura Lyman; Green, Eric D.] NHGRI, NIH, Bethesda, MD 20892 USA. [Abramowicz, Marc] Univ Libre Bruxelles, B-1070 Brussels, Belgium. [Al-Mulla, Fahd] Kuwait Univ, Genatak Global Med Clin, Kuwait 46300, Kuwait. [Anderson, Warwick] Nat Hlth & Med Res Council, Canberra, ACT 2601, Australia. [Balling, Rudi] Univ Luxembourg, Luxembourg Ctr Syst Biomed, L-4362 Esch Sur Alzette, Luxembourg. [Berger, Adam C.] Inst Med, Board Hlth Sci Policy, Washington, DC 20001 USA. [Bleyl, Steven] Intermt Healthcare, Salt Lake City, UT 84111 USA. [Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Chantratita, Wasun] Mahidol Univ, Ramathibodi Hosp, Bangkok 10400, Thailand. [Chisholm, Rex L.] Northwestern Univ Feinberg, Sch Med, Ctr Genet Med, Chicago, IL 60611 USA. [Dissanayake, Vajira H. W.] Univ Colombo, Fac Med, Human Genet Unit, Colombo 00800, Sri Lanka. [Dunn, Michael] Wellcome Trust Res Labs, Genet & Mol Sci, London NW1 2BE, England. [Dzau, Victor J.] Nat Acad Med, Washington, DC 20001 USA. [Han, Bok-Ghee] Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do 363951, South Korea. [Hubbard, Tim] Kings Coll London, London SE1 9RT & Genom England, Dept Med & Mol Genet, London EC1M 6BQ, England. [Kolbe, Anne] Natl Hlth Comm, Auckland 1050, New Zealand. [Korf, Bruce] Univ Alabama Birmingham, Ctr Genom Sci, Birmingham, AL 35294 USA. [Kubo, Michiaki] RIKEN, Ctr Integrat Med Sci IMS, Yokohama, Kanagawa 2300045, Japan. [Lasko, Paul] Canadian Inst Hlth Res, Inst Genet, Montreal, PQ H3A 0G4, Canada. [Lasko, Paul] McGill Univ, Montreal, PQ H3A 0G4, Canada. [Leego, Erkki; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia. [Mahasirimongkol, Surakameth] Minist Publ Hlth, Dept Med Sci, Nonthaburi 11000, Thailand. [Majumdar, Partha P.] Nat Inst Biomed Genom, Kalyani 741251, W Bengal, India. [Majumdar, Partha P.] Indian Stat Inst, Kalyani 741251, W Bengal, India. [Matthijs, Gert] Univ Leuven, KU Leuven, Ctr Human Genet, B-3000 Leuven, Belgium. [McLeod, Howard L.] Mofitt Canc Ctr, DeBartolo Family Personalized Med Inst, Tampa, FL 33612 USA. [Meulien, Pierre] Genome Canada, Ottawa, ON K2P 1P1, Canada. [Miyano, Satoru] Univ Tokyo, Inst Med Sci, Tokyo 1088639, Japan. [Naparstek, Yaakov] Hadassah Hebrew Univ Hosp, Res & Acad Affairs, IL-91120 Jerusalem, Israel. [O'Rourke, P. Pearl] Partners HealthCare, Off Human Res Affairs, Boston, MA 02199 USA. [Patrinos, George P.] Univ Patras, Sch Hlth Sci, Dept Pharm, Patras 26504, Greece. [Rehm, Heidi L.] Partners Healthcare Syst, Mol Med Lab, Boston, MA 02139 USA. [Relling, Mary V.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Rennert, Gad] Clalit Natl Personalized Med Program, Carmel Med Ctr, Dept Community Med & Epidemiol, IL-34362 Haifa, Israel. [Roden, Dan M.] Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. [Shuldiner, Alan R.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Sinha, Sukdeb] Minist Sci & Technol Govt, Dept Biotechnol, New Delhi 110003, India. [Tan, Patrick] Duke Natl Univ Singapore, Grad Sch Med, Singapore 169857, Singapore. [Ulfendahl, Mats] Swedish Res Council, SE-10138 Stockholm, Sweden. [Ward, Robyn] Univ Queensland, St Lucia, Qld 4067, Australia. [Williams, Marc S.] Genom Med Inst, Geisinger Hlth Syst, Danville, PA 18510 USA. [Wong, John E. L.] Natl Univ Singapore, Singapore 119228, Singapore. [Ginsburg, Geoffrey S.] Duke Univ, Ctr Appl Genom & Precis Med, Durham, NC 27710 USA. RP Manolio, TA (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM manolio@nih.gov; geoffrey.ginsburg@dm.duke.edu RI Hubbard, Tim/C-2567-2008; Lasko, Paul/C-6761-2014; Kubo, Michiaki/N-7947-2015; Ward, Robyn/I-2313-2013; OI Hubbard, Tim/0000-0002-1767-9318; Lasko, Paul/0000-0002-4037-3501; Ward, Robyn/0000-0002-6877-8906; Abramowicz, Marc/0000-0003-0623-8768 FU Intramural NIH HHS [Z99 HG999999]; NHGRI NIH HHS [U01 HG006388] NR 44 TC 17 Z9 18 U1 2 U2 23 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 JUN 3 PY 2015 VL 7 IS 290 AR 290ps13 DI 10.1126/scitranslmed.aab0194 PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CJ6WI UT WOS:000355635500001 PM 26041702 ER PT J AU Oliveira, F Rowton, E Aslan, H Gomes, R Castrovinci, PA Alvarenga, PH Abdeladhim, M Teixeira, C Meneses, C Kleeman, LT Guimaraes-Costa, AB Rowland, TE Gilmore, D Doumbia, S Reed, SG Lawyer, PG Andersen, JF Kamhawi, S Valenzuela, JG AF Oliveira, Fabiano Rowton, Edgar Aslan, Hamide Gomes, Regis Castrovinci, Philip A. Alvarenga, Patricia H. Abdeladhim, Maha Teixeira, Clarissa Meneses, Claudio Kleeman, Lindsey T. Guimaraes-Costa, Anderson B. Rowland, Tobin E. Gilmore, Dana Doumbia, Seydou Reed, Steven G. Lawyer, Phillip G. Andersen, John F. Kamhawi, Shaden Valenzuela, Jesus G. TI A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; PHLEBOTOMUS-PAPATASI; VISCERAL LEISHMANIASIS; IMMUNE-RESPONSE; MAJOR INFECTION; LUTZOMYIA-LONGIPALPIS; CYTOKINE PRODUCTION; PROTECTION; FLIES; ANTIGEN AB Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with salivary protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly-exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4(+)IFN-gamma(+) lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis. C1 [Oliveira, Fabiano; Aslan, Hamide; Gomes, Regis; Castrovinci, Philip A.; Abdeladhim, Maha; Teixeira, Clarissa; Meneses, Claudio; Kleeman, Lindsey T.; Guimaraes-Costa, Anderson B.; Gilmore, Dana; Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Rowton, Edgar; Rowland, Tobin E.; Lawyer, Phillip G.] Walter Reed Army Inst Res, Dept Entomol, Silver Spring, MD 20910 USA. [Gomes, Regis; Teixeira, Clarissa] Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz CPqGM, BR-40296710 Salvador, BA, Brazil. [Alvarenga, Patricia H.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Lab Bioquim Resposta Estresse, BR-21941902 Rio De Janeiro, Brazil. [Alvarenga, Patricia H.] Univ Fed Rio de Janeiro, INCT EM, BR-21941902 Rio De Janeiro, Brazil. [Doumbia, Seydou] Univ Bamako, Fac Med Pharm & Odontostomatol, Bamako 1805, Mali. [Reed, Steven G.] Infectious Dis Res Inst, Seattle, WA 98102 USA. [Andersen, John F.] NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM skamhawi@niaid.nih.gov; jvalenzuela@niaid.nih.gov FU Intramural Research Program at the NIAID, NIH; Grand Challenges Explorations grant from the Bill and Melinda Gates Foundation; Science Without Borders Fellowship from the National Council for Scientific and Technological Development (CNPq)-Brazil FX Support for this work was provided by the Intramural Research Program at the NIAID, NIH, and by the Grand Challenges Explorations grant from the Bill and Melinda Gates Foundation. A.B.G.-C. was partially funded by a Science Without Borders Fellowship from the National Council for Scientific and Technological Development (CNPq)-Brazil. Fundacao de Amparo a Pesquisa do Rio de Janeiro Carlos Chagas Filho and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (P.H.A.). NR 59 TC 13 Z9 13 U1 1 U2 13 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 JUN 3 PY 2015 VL 7 IS 290 AR 290ra90 DI 10.1126/scitranslmed.aaa3043 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CJ6WI UT WOS:000355635500009 PM 26041707 ER PT J AU Wasserman, D AF Wasserman, David TI Disability, Diversity, and Preference for the Status Quo: Bias or Justifiable Preference? SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Wasserman, David] NIH, Bethesda, MD 20982 USA. RP Wasserman, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20982 USA. EM dtwasserm@gmail.com NR 5 TC 0 Z9 0 U1 2 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JUN 3 PY 2015 VL 15 IS 6 BP 11 EP 12 DI 10.1080/15265161.2015.1028676 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CJ3TN UT WOS:000355407000003 PM 26030485 ER PT J AU Bayefsky, MJ AF Bayefsky, Michelle J. TI Imposing Genetic Diversity: An Imposition on Reproductive Freedom SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Bayefsky, Michelle J.] NIH, Washington, DC 20008 USA. RP Bayefsky, MJ (reprint author), NIH, Dept Bioeth, 2950 Van Ness St NW 704, Washington, DC 20008 USA. EM michelle.bayefsky@nih.gov NR 6 TC 0 Z9 0 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JUN 3 PY 2015 VL 15 IS 6 BP 27 EP 28 DI 10.1080/15265161.2015.1028662 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA CJ3TN UT WOS:000355407000010 PM 26030492 ER PT J AU Atienza, AA Zarcadoolas, C Vaughon, W Hughes, P Patel, V Chou, WYS Pritts, J AF Atienza, Audie A. Zarcadoolas, Christina Vaughon, Wendy Hughes, Penelope Patel, Vaishali Chou, Wen-Ying Sylvia Pritts, Joy TI Consumer Attitudes and Perceptions on mHealth Privacy and Security: Findings From a Mixed-Methods Study SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID RECORDS AB This study examined consumers' attitudes and perceptions regarding mobile health (mHealth) technology use in health care. Twenty-four focus groups with 256 participants were conducted in 5 geographically diverse locations. Participants were also diverse in age, education, race/ethnicity, gender, and rural versus urban settings. Several key themes emerged from the focus groups. Findings suggest that consumer attitudes regarding mHealth privacy/security are highly contextualized, with concerns depending on the type of information being communicated, where and when the information is being accessed, who is accessing or seeing the information, and for what reasons. Consumers frequently considered the tradeoffs between the privacy/security of using mHealth technologies and the potential benefits. Having control over mHealth privacy/security features and trust in providers were important issues for consumers. Overall, this study found significant diversity in attitudes regarding mHealth privacy/security both within and between traditional demographic groups. Thus, to address consumers' concerns regarding mHealth privacy and security, a one-size-fits-all approach may not be adequate. Health care providers and technology developers should consider tailoring mHealth technology according to how various types of information are communicated in the health care setting, as well as according to the comfort, skills, and concerns individuals may have with mHealth technology. C1 [Atienza, Audie A.; Chou, Wen-Ying Sylvia] NCI, NIH, Rockville, MD 20892 USA. [Zarcadoolas, Christina; Vaughon, Wendy] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA. [Hughes, Penelope; Patel, Vaishali; Pritts, Joy] US Dept HHS, Off Natl Coordinator Hlth Informat Technol, Washington, DC 20201 USA. RP Atienza, AA (reprint author), NCI, Sci Res & Technol Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, 9609 Med Ctr Dr 3E608, Rockville, MD 20892 USA. EM atienzaa@mail.nih.gov FU Department of Health and Human Services, Office of the National Coordinator for Health Information Technology FX This study was not supported by external funding. The Department of Health and Human Services, Office of the National Coordinator for Health Information Technology provided funds for the data collection. The National Cancer Institute, the Department of Health and Human Services, and the Office of the National Coordinator for Health Information Technology reviewed and approved this article before submission. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Department of Health and Human Services, the National Institutes of Health, or the National Cancer Institute. NR 30 TC 6 Z9 6 U1 1 U2 15 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PD JUN 3 PY 2015 VL 20 IS 6 BP 673 EP 679 DI 10.1080/10810730.2015.1018560 PG 7 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA CJ0RS UT WOS:000355186000006 PM 25868685 ER PT J AU Gold, PW Pavlatou, MG Michelson, D Mouro, CM Kling, MA Wong, ML Licinio, J Goldstein, SA AF Gold, P. W. Pavlatou, M. G. Michelson, D. Mouro, C. M. Kling, M. A. Wong, M-L Licinio, J. Goldstein, S. A. TI Chronic administration of anticonvulsants but not antidepressants impairs bone strength: clinical implications SO TRANSLATIONAL PSYCHIATRY LA English DT Review ID SYMPATHETIC-NERVOUS-SYSTEM; SEROTONIN-REUPTAKE INHIBITORS; MINERAL DENSITY; MAJOR DEPRESSION; BIOCHEMICAL MANIFESTATIONS; WOMEN; RISK; INTERLEUKIN-6; NEUROBIOLOGY; FRACTURES AB Major depression and bipolar disorder are associated with decreased bone mineral density (BMD). Antidepressants such as imipramine (IMIP) and specific serotonin reuptake inhibitors (SSRIs) have been implicated in reduced BMD and/or fracture in older depressed patients. Moreover, anticonvulsants such as valproate (VAL) and carbamazepine (CBZ) are also known to increase fracture rates. Although BMD is a predictor of susceptibility to fracture, bone strength is a more sensitive predictor. We measured mechanical and geometrical properties of bone in 68 male Sprague Dawley rats on IMIP, fluoxetine (FLX), VAL, CBZ, CBZ vehicle and saline (SAL), given intraperitoneally daily for 8 weeks. Distinct regions were tested to failure by four-point bending, whereas load displacement was used to determine stiffness. The left femurs were scanned in a MicroCT system to calculate mid-diaphyseal moments of inertia. None of these parameters were affected by antidepressants. However, VAL resulted in a significant decrease in stiffness and a reduction in yield, and CBZ induced a decrease in stiffness. Only CBZ induced alterations in mechanical properties that were accompanied by significant geometrical changes. These data reveal that chronic antidepressant treatment does not reduce bone strength, in contrast to chronic anticonvulsant treatment. Thus, decreased BMD and increased fracture rates in older patients on antidepressants are more likely to represent factors intrinsic to depression that weaken bone rather than antidepressants per se. Patients with affective illness on anticonvulsants may be at particularly high risk for fracture, especially as they grow older, as bone strength falls progressively with age. C1 [Gold, P. W.; Pavlatou, M. G.] NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. [Michelson, D.] Merck, Whitehouse Stn, NJ USA. [Mouro, C. M.; Goldstein, S. A.] Univ Michigan, Orthopaed Res Labs, Ann Arbor, MI 48109 USA. [Kling, M. A.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. [Kling, M. A.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Wong, M-L; Licinio, J.] Australian Natl Univ, John Curtin Sch Med Res, Dept Translat Med, Canberra, ACT 2601, Australia. RP Gold, PW (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, 10 Ctr Dr,Room 2D46, Bethesda, MD 20892 USA. EM philipgold@mail.nih.gov OI Kling, Mitchel/0000-0002-2232-1409 FU Clinical Neuroendocrinology Branch, National Institute of Mental Health, NIH [AR34399]; Whittaker Foundation; National Institute of Aging, NIA [T32 AG00114]; GAANN FX We acknowledge the substantial contributions of Erica Smith and Cameron Mouro for conducting many of the MicroCT and mechanical tests. We also acknowledge Mark Stock and Rick Zanecki for their technical assistance. This work was supported by funding from the Clinical Neuroendocrinology Branch, National Institute of Mental Health, NIH AR34399, the Whittaker Foundation and a Multidisciplinary Research Training Grant in Aging from the National Institute of Aging, NIA T32 AG00114 and a GAANN Fellowship. NR 29 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD JUN 2 PY 2015 VL 5 AR e576 DI 10.1038/tp.2015.38 PG 6 WC Psychiatry SC Psychiatry GA DA2WQ UT WOS:000367658300003 PM 26035060 ER PT J AU Peng, YC Wane, BB Talaae, K Karron, R Powell, TJ Zeng, H Dong, DN Luke, CJ McMichael, A Subbarao, K Dong, T AF Peng, YanChun Wane, Beibei Talaae, Kawsar Karron, Ruth Powell, Timothy J. Zeng, Hui Dong, Danning Luke, Catherine J. McMichael, Andrew Subbarao, Kanta Dong, Tao TI Boosted influenza-specific T cell responses after H5N1 pandemic live attenuated influenza virus vaccination SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE influenza; H5N1; vaccine; T cells; LAIV; peptide; epitope; antigenic sin ID A H7N9 VIRUS; YOUNG-CHILDREN; INFECTION; EFFICACY; VACCINES; IMMUNITY; PROTECTION; CORRELATE AB Background: In a phase I clinical trial, a H5N1 pandemic live attenuated influenza virus (pLAIV) VN2004 vaccine bearing avian influenza H5N1 hemagglutinin (HA) and NA genes on the A/Ann Arbor cold-adapted vaccine backbone displayed very restricted replication. We evaluated T cell responses to H5N1 pLAIV vaccination and assessed pre-existing T cell responses to determine whether they were associated with restricted replication of the H5N1 pLAIV. Method: ELISPOT assays were performed using pools of overlapping peptides spanning the entire H5N1 proteome and the HA proteins of relevant seasonal H1N1 and H3N2 viruses. We tested stored peripheral blood mononuclear cells (PBMCs) from 21 study subjects who received two doses of the H5N1 pLAIV. The PBMCs were collected 1 day before and 7 days after the first and second pLAIV vaccine doses, respectively. Result: T cell responses to conserved internal proteins M and NP were significantly boosted by vaccination (p = 0.036). In addition, H5N1 pLAIV appeared to preferentially stimulate and boost pre-existing seasonal influenza virus HA-specific T cell responses that showed low cross-reactivity with the H5 HA. We confirmed this observation by T cell cloning and identified a novel HA-specific epitope. However, we did not find any evidence that pre-existing T cells prevented pLAIV replication and take. Conclusion: We found that cross-reactive T cell responses could be boosted by pLAIV regardless of the induction of antibody. The impact of the "original antigenic sin" phenomenon in a subset of volunteers, with preferential expansion of seasonal influenza-specific but not H5N1-specific T cell responses merits further investigation. C1 [Peng, YanChun; Wane, Beibei; Powell, Timothy J.; Dong, Danning; McMichael, Andrew; Dong, Tao] Univ Oxford, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford YANCHUN PEN, England. [Wane, Beibei; Zeng, Hui] Capital Med Univ, Beijing Ditan Hosp, Inst Infect Dis, Beijing, Peoples R China. [Talaae, Kawsar; Karron, Ruth] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD USA. [Luke, Catherine J.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3E13C-1,33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov; tao.dong@imm.ox.ac.uk FU Medical Research Council, UK; Division of Intramural Research, NIAID, NIH FX This research was supported in part by the Medical Research Council, UK and the Division of Intramural Research, NIAID, NIH. NR 23 TC 1 Z9 1 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD JUN 2 PY 2015 VL 6 BP 1 EP 9 AR 287 DI 10.3389/fimmu.2015.00287 PG 9 WC Immunology SC Immunology GA CL7MB UT WOS:000357155100001 PM 26082783 ER PT J AU Song, SM Graham-Engeland, JE Corwin, EJ Ceballos, RM Taylor, SE Seeman, T Klein, LC AF Song, Sunmi Graham-Engeland, Jennifer E. Corwin, Elizabeth J. Ceballos, Rachel M. Taylor, Shelley E. Seeman, Teresa Klein, Laura Cousino TI The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor SO PEERJ LA English DT Article DE Stress; Multiple negative social relationships; Hostility; Inflammatory cytokine response; Depressed mood; A Trier Social Stress Task ID GENE-EXPRESSION; HOSTILITY; HEALTH; INTERLEUKIN-6; WOMEN; MEN; AGE AB The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-alpha from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood. C1 [Song, Sunmi] NHGRI, Social Behav Res Branch, NIH, Bethesda, MD USA. [Graham-Engeland, Jennifer E.; Klein, Laura Cousino] Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. [Corwin, Elizabeth J.] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA. [Ceballos, Rachel M.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA USA. [Taylor, Shelley E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Seeman, Teresa] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Klein, Laura Cousino] Penn State Univ, Penn State Inst Neurosci, University Pk, PA 16802 USA. RP Klein, LC (reprint author), Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. EM lcklein@psu.edu FU General Clinical Research Center of The Pennsylvania State University (NIH) [MO1-RR-10732]; National Science Foundataion [SBR9905157]; College of Health and Human Development of The Pennsylvania State University [223-15-3605]; Kligman Graduate Fellowship via the College of Health and Human Development at The Pennsylvania State University FX This research was conducted at The Pennsylvania State University. Funding was provided by the General Clinical Research Center of The Pennsylvania State University (NIH grant MO1-RR-10732). Funding was also provided by the National Science Foundataion (SBR9905157; SET and LCK) and a grant from the College of Health and Human Development of The Pennsylvania State University (223-15-3605; LCK and EJC). The first author is currently a postdoctoral fellow at the Social and Behavioral Research Branch at the National Human Genome Research Institute and was supported by a Kligman Graduate Fellowship via the College of Health and Human Development at The Pennsylvania State University (S Song). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 0 Z9 0 U1 1 U2 1 PU PEERJ INC PI LONDON PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND SN 2167-8359 J9 PEERJ JI PeerJ PD JUN 2 PY 2015 VL 3 AR e959 DI 10.7717/peerj.959 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CK6OL UT WOS:000356347300001 PM 26056615 ER PT J AU Byrd, AL Segre, JA AF Byrd, Allyson L. Segre, Julia A. TI Elucidating microbial codes to distinguish individuals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID HUMAN GUT MICROBIOME; ENTEROTYPES C1 [Byrd, Allyson L.; Segre, Julia A.] NHGRI, Microbial Genom Sect, Translat & Funct Genom Branch, Bethesda, MD 20892 USA. [Byrd, Allyson L.] Boston Univ, Dept Bioinformat, Boston, MA 02215 USA. RP Segre, JA (reprint author), NHGRI, Microbial Genom Sect, Translat & Funct Genom Branch, Bethesda, MD 20892 USA. EM jsegre@nhgri.nih.gov NR 14 TC 1 Z9 1 U1 1 U2 12 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 JUN 2 PY 2015 VL 112 IS 22 BP 6778 EP 6779 DI 10.1073/pnas.1507731112 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ9OO UT WOS:000355832200027 PM 26015565 ER PT J AU Tian, HY Zhou, S Dong, L Van Boeckel, TP Cui, YJ Newman, SH Takekawa, JY Prosser, DJ Xiao, XM Wu, YR Cazelles, B Huang, SQ Yang, RF Grenfell, BT Xu, B AF Tian, Huaiyu Zhou, Sen Dong, Lu Van Boeckel, Thomas P. Cui, Yujun Newman, Scott H. Takekawa, John Y. Prosser, Diann J. Xiao, Xiangming Wu, Yarong Cazelles, Bernard Huang, Shanqian Yang, Ruifu Grenfell, Bryan T. Xu, Bing TI Avian influenza H5N1 viral and bird migration networks in Asia (vol 112, pg 172, 2014) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Correction C1 [Tian, Huaiyu; Huang, Shanqian; Xu, Bing] Beijing Normal Univ, Coll Global Change & Earth Syst Sci, State Key Lab Remote Sensing Sci, Beijing 100875, Peoples R China. [Zhou, Sen; Xu, Bing] Tsinghua Univ, Ctr Earth Syst Sci, Key Lab Earth Syst Modelling, Minist Educ, Beijing 100084, Peoples R China. [Zhou, Sen; Xu, Bing] Tsinghua Univ, Sch Environm, Beijing 100084, Peoples R China. [Dong, Lu] Beijing Normal Univ, Coll Life Sci, Key Lab Biodivers & Ecol Engn, Minist Educ, Beijing 100875, Peoples R China. [Van Boeckel, Thomas P.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Cui, Yujun; Wu, Yarong; Yang, Ruifu] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing 100071, Peoples R China. [Newman, Scott H.] ECTAD, Food & Agr Org United Nations, Hanoi 10000, Vietnam. [Takekawa, John Y.] US Geol Survey, Western Ecol Res Ctr, Vallejo, CA 94592 USA. [Takekawa, John Y.] Natl Audubon Soc, Div Sci, San Francisco, CA 94104 USA. [Prosser, Diann J.] US Geol Survey, Patuxent Wildlife Res Ctr, Beltsville, MD 20705 USA. [Xiao, Xiangming] Univ Oklahoma, Dept Microbiol & Plant Biol, Norman, OK 73019 USA. [Xiao, Xiangming] Fudan Univ, Inst Biodivers Sci, Shanghai 200433, Peoples R China. [Cazelles, Bernard] Univ Paris 06, CNRS, Ecol & Evolut, UMR 7625, F-75230 Paris 05, France. [Cazelles, Bernard] Ecole Normale Super, F-75230 Paris 05, France. [Cazelles, Bernard] Inst Rech Dev, Unite Modelisat Math & Informat Syst Complexes, Unite Mixte Int 209, F-93142 Bondy, France. [Cazelles, Bernard] Univ Paris 06, F-93142 Bondy, France. [Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Xu, Bing] Univ Utah, Dept Geog, Salt Lake City, UT 84112 USA. RP Tian, HY (reprint author), Beijing Normal Univ, Coll Global Change & Earth Syst Sci, State Key Lab Remote Sensing Sci, Beijing 100875, Peoples R China. RI Cazelles, Bernard/B-1572-2013; Tian, Huaiyu/G-1934-2016 OI Cazelles, Bernard/0000-0002-7972-361X; FU NICHD NIH HHS [P2C HD047879] NR 1 TC 0 Z9 0 U1 2 U2 16 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 JUN 2 PY 2015 VL 112 IS 22 BP E2980 EP E2980 DI 10.1073/pnas.1505041112 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CJ9OO UT WOS:000355832200022 PM 25964339 ER PT J AU Best, RB Hofmann, H Nettels, D Schuler, B AF Best, Robert B. Hofmann, Hagen Nettels, Daniel Schuler, Benjamin TI Quantitative Interpretation of FRET Experiments via Molecular Simulation: Force Field and Validation SO BIOPHYSICAL JOURNAL LA English DT Article ID INTRINSICALLY DISORDERED PROTEINS; RESONANCE ENERGY-TRANSFER; DER-WAALS INTERACTIONS; FLUORESCENCE SPECTROSCOPY; UNFOLDED PROTEINS; INTERNAL-FRICTION; PHOTON STATISTICS; DYNAMICS; COLLAPSE; MODEL AB Molecular simulation is a valuable and complementary tool that may assist with the interpretation of single-molecule Forster resonance energy transfer (FRET) experiments, if the energy function is of sufficiently high quality. Here we present force-field parameters for one of the most common pairs of chromophores used in experiments, AlexaFluor 488 and 594. From microsecond molecular-dynamics simulations, we are able to recover both experimentally determined equilibrium constants and association/dissociation rates of the chromophores with free tryptophan, as well as the decay of fluorescence anisotropy of a labeled protein. We find that it is particularly important to obtain a correct balance of solute-water interactions in the simulations in order to faithfully capture the experimental anisotropy decays, which provide a sensitive benchmark for fluorophore mobility. Lastly, by a combination of experiment and simulation, we address a potential complication in the interpretation of experiments on polyproline, used as a molecular ruler for FRET experiments, namely the potential association of one of the chromophores with the polyproline helix. Under conditions where simulations accurately capture the fluorescence anisotropy decay, we find at most a modest, transient population of conformations in which the chromophores associate with the polyproline. Explicit calculation of FRET transfer efficiencies for short polyprolines yields results in good agreement with experiment. These results illustrate the potential power of a combination of molecular simulation and experiment in quantifying biomolecular dynamics. C1 [Best, Robert B.] Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Hofmann, Hagen; Nettels, Daniel; Schuler, Benjamin] Univ Zurich, Dept Biochem, Zurich, Switzerland. RP Best, RB (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertbe@helix.nih.gov; schuler@bioc.uzh.ch RI Schuler, Benjamin/E-7342-2011; Best, Robert/H-7588-2016 OI Schuler, Benjamin/0000-0002-5970-4251; Best, Robert/0000-0002-7893-3543 FU Intramural Research Program of the National Institutes of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; Swiss National Science Foundation FX R.B. was supported by the Intramural Research Program of the National Institutes of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. B.S. was supported by the Swiss National Science Foundation. NR 74 TC 10 Z9 10 U1 5 U2 37 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JUN 2 PY 2015 VL 108 IS 11 BP 2721 EP 2731 DI 10.1016/j.bpj.2015.04.038 PG 11 WC Biophysics SC Biophysics GA CJ7IQ UT WOS:000355668800013 PM 26039173 ER PT J AU Pepper, DJ AF Pepper, Dominique J. TI Treatment for Hospitalized Patients With Severe Community-Acquired Pneumonia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID SEPTIC SHOCK; MANAGEMENT C1 [Pepper, Dominique J.] NIH, Bethesda, MD 20892 USA. RP Pepper, DJ (reprint author), NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. EM dominiquepepper@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 2 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 JUN 2 PY 2015 VL 313 IS 21 BP 2184 EP 2184 DI 10.1001/jama.2015.4774 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CJ4CC UT WOS:000355430900024 PM 26034964 ER PT J AU Chen, RJ Zhao, A Chen, HL Zhao, ZH Cai, J Wang, CC Yang, CY Li, HC Xu, XH Ha, SD Li, TT Kan, HD AF Chen, Renjie Zhao, Ang Chen, Honglei Zhao, Zhuohui Cai, Jing Wang, Cuicui Yang, Changyuan Li, Huichu Xu, Xiaohui Ha, Sandie Li, Tiantian Kan, Haidong TI Cardiopulmonary Benefits of Reducing Indoor Particles of Outdoor Origin SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE air pollution; air purification; cardiovascular health; intervention; pulmonary health; randomized controlled trial ID PARTICULATE AIR-POLLUTION; PULMONARY-FUNCTION; OXIDATIVE STRESS; HEALTHY-ADULTS; LUNG-FUNCTION; INFLAMMATION; FILTRATION; PRESSURE; EXPOSURE; VASOCONSTRICTION AB BACKGROUND Indoor exposure to fine particulate matter (PM2.5) from outdoor sources is a major health concern, especially in highly polluted developing countries such as China. Few studies have evaluated the effectiveness of indoor air purification on the improvement of cardiopulmonary health in these areas. OBJECTIVES This study sought to evaluate whether a short-term indoor air purifier intervention improves cardiopulmonary health. METHODS We conducted a randomized, double-blind crossover trial among 35 healthy college students in Shanghai, China, in 2014. These students lived in dormitories that were randomized into 2 groups and alternated the use of true or sham air purifiers for 48 h with a 2-week washout interval. We measured 14 circulating biomarkers of inflammation, coagulation, and vasoconstriction; lung function; blood pressure (BP); and fractional exhaled nitric. We applied linear mixed-effect models to evaluate the effect of the intervention on health outcome variables. RESULTS On average, air purification resulted in a 57% reduction in PM2.5 concentration, from 96.2 to 41.3 mg/m(3), within hours of operation. Air purification was significantly associated with decreases in geometric means of several circulating inflammatory and thrombogenic biomarkers, including 17.5% in monocyte chemoattractant protein-1, 68.1% in interleukin-1 beta, 32.8% in myeloperoxidase, and 64.9% in soluble CD40 ligand. Furthermore, systolic BP, diastolic BP, and fractional exhaled nitrous oxide were significantly decreased by 2.7%, 4.8%, and 17.0% in geometric mean, respectively. The impacts on lung function and vasoconstriction biomarkers were beneficial but not statistically significant. CONCLUSIONS This intervention study demonstrated clear cardiopulmonary benefits of indoor air purification among young, healthy adults in a Chinese city with severe ambient particulate air pollution. (C) 2015 by the American College of Cardiology Foundation. C1 [Chen, Renjie; Zhao, Ang; Zhao, Zhuohui; Cai, Jing; Wang, Cuicui; Yang, Changyuan; Li, Huichu; Kan, Haidong] Fudan Univ, Sch Publ Hlth, Key Lab Publ Hlth Safety, Minist Educ, Shanghai 200032, Peoples R China. [Chen, Renjie; Kan, Haidong] Fudan Univ, Shanghai Key Lab Atmospher Particle Pollut & Prev, Shanghai 200032, Peoples R China. [Chen, Renjie; Kan, Haidong] Fudan Univ, Key Lab Hlth Technol Assessment, Minist Hlth, Shanghai 200032, Peoples R China. [Chen, Honglei] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Xu, Xiaohui; Ha, Sandie] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Epidemiol, Gainesville, FL USA. [Xu, Xiaohui; Ha, Sandie] Univ Florida, Coll Med, Gainesville, FL USA. [Li, Tiantian] Chinese Ctr Dis Control & Prevent, Inst Environm Hlth & Related Prod Safety, Beijing, Peoples R China. RP Kan, HD (reprint author), Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, POB 249,130 Dong An Rd, Shanghai 200032, Peoples R China. EM haidongkan@gmail.com RI 刘, 李陆/H-8469-2015 FU National Natural Science Foundation of China [81222036]; China Medical Board Collaborating Program [13-152]; Cyrus Tang Foundation [CTF-FD2014001]; Public Welfare Research Program of National Health and Family Planning Commission of China [201402022]; intramural research program of the U.S. National Institutes of Health, National Institute of Environmental Health Sciences FX The National Natural Science Foundation of China (81222036), China Medical Board Collaborating Program (13-152), Cyrus Tang Foundation (CTF-FD2014001), and Public Welfare Research Program of National Health and Family Planning Commission of China (201402022) supported this study. Dr. H. Chen is supported by the intramural research program of the U.S. National Institutes of Health, National Institute of Environmental Health Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. R. Chen and Mr. Zhao contributed equally to this work. NR 28 TC 14 Z9 15 U1 13 U2 64 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 JUN 2 PY 2015 VL 65 IS 21 BP 2279 EP 2287 DI 10.1016/j.jacc.2015.03.553 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CJ0VH UT WOS:000355196300003 PM 26022815 ER PT J AU Shah, SK Wilfond, BS AF Shah, Seema K. Wilfond, Benjamin S. TI HIV REMISSION IN NEONATES ethical and human rights considerations SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Editorial Material C1 [Shah, Seema K.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD USA. [Shah, Seema K.] NIH, Div Aids, Bethesda, MD USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Wilfond, Benjamin S.] Trueman Katz Ctr Pediat Bioeth, Seattle, WA USA. RP Wilfond, BS (reprint author), Seattle Childrens Res Inst, Trueman Katz Ctr Pediat Bioeth, M-S JMB 6,1900 Ninth Ave, Seattle, WA 98101 USA. EM benjamin.wilfond@seattlechildrens.org NR 1 TC 1 Z9 1 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0031-5982 EI 1529-8795 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD SUM PY 2015 VL 58 IS 3 SI SI BP 341 EP 343 PG 3 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA DL2ZV UT WOS:000375504800011 ER PT J AU Shah, SK Wilfond, BS AF Shah, Seema K. Wilfond, Benjamin S. TI THE ROLE OF COMMUNITY ENGAGEMENT IN NOVEL HIV RESEARCH IN INFANTS SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Article ID DEVELOPING-COUNTRIES AB The proposed study would be a single-arm interventional trial in a community where HIV is endemic. Beginning with a high-dose triple-drug treatment right after birth, treatment would continue in those who test HIV positive for the next two years and then stop to see if HIV has been eradicated. While we believe the general approach can be justified, and some important questions about this study have already been raised in the literature, three additional questions need to be addressed to determine an ethically sound study design. First is whether this study will be perceived by the community as an opportunity or a burden. A second question regards the ideal permission process and whether permission should be obtained by someone who is not involved in clinical care.A third question regards the implications of withdrawing from a study that involves treatment discontinuation and the expectations of the participants and community, about subsequent obligations of the researchers. For these questions, there may be more than one acceptable approach, and the critical issue is to work with the community respectfully and as a partner in the study design process. C1 [Shah, Seema K.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD USA. [Shah, Seema K.] NIH, Div Aids, Bethesda, MD USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Wilfond, Benjamin S.] Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA. RP Wilfond, BS (reprint author), Seattle Childrens Res Inst, Truernan Katz Ctr Pediat Bioeth, M-S JMB 6,1900 Ninth Ave, Seattle, WA 98101 USA. EM benjamin.wilfond@seatdechildrens.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0031-5982 EI 1529-8795 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD SUM PY 2015 VL 58 IS 3 SI SI BP 344 EP 347 PG 4 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA DL2ZV UT WOS:000375504800012 ER PT J AU Shirota, H Tross, D Klinman, DM AF Shirota, Hidekazu Tross, Debra Klinman, Dennis M. TI CpG Oligonucleotides as Cancer Vaccine Adjuvants SO VACCINES LA English DT Review DE CpG; TLR; vaccine; cancer ID PLASMACYTOID DENDRITIC CELLS; REGULATORY T-CELLS; TOLL-LIKE RECEPTORS; IMIQUIMOD 5-PERCENT CREAM; IN-SITU VACCINATION; SUPPRESSOR-CELLS; MELANOMA PATIENTS; B-CELL; ANTITUMOR IMMUNITY; NY-ESO-1 PROTEIN AB Adjuvants improve host responsiveness to co-delivered vaccines through a variety of mechanisms. Agents that trigger cells expressing Toll-like receptors (TLR) activate an innate immune response that enhances the induction of vaccine-specific immunity. When administered in combination with vaccines designed to prevent or slow tumor growth, TLR agonists have significantly improved the generation of cytotoxic T lymphocytes. Unfortunately, vaccines containing TLR agonists have rarely been able to eliminate large established tumors when administered systemically. To improve efficacy, attention has focused on delivering TLR agonists intra-tumorally with the intent of altering the tumor microenvironment. Agonists targeting TLRs 7/8 or 9 can reduce the frequency of Tregs while causing immunosuppressive MDSC in the tumor bed to differentiate into tumoricidal macrophages thereby enhancing tumor elimination. This work reviews pre-clinical and clinical studies concerning the utility of TLR 7/8/9 agonists as adjuvants for tumor vaccines. C1 [Shirota, Hidekazu] Tohoku Univ Hosp, Dept Clin Oncol, Sendai, Miyagi 9808577, Japan. [Tross, Debra; Klinman, Dennis M.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. EM Shirota@idac.tohoku.ac.jp; Trossd@mail.nih.gov; klinmand@mail.nih.gov NR 128 TC 5 Z9 5 U1 3 U2 12 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2076-393X J9 VACCINES JI Vaccines PD JUN PY 2015 VL 3 IS 2 BP 390 EP 407 DI 10.3390/vaccines3020390 PG 18 WC Immunology SC Immunology GA DG0XR UT WOS:000371789900009 PM 26343193 ER PT J AU Rogers, T Ratnayaka, K Schenke, WH Sonmez, M Kocaturk, O Mazal, JR Chen, MY Flugelman, MY Troendle, JF Faranesh, AZ Lederman, RJ AF Rogers, Toby Ratnayaka, Kanishka Schenke, William H. Sonmez, Merdim Kocaturk, Ozgur Mazal, Jonathan R. Chen, Marcus Y. Flugelman, Moshe Y. Troendle, James F. Faranesh, Anthony Z. Lederman, Robert J. TI Fully Percutaneous Transthoracic Left Atrial Entry and Closure as a Potential Access Route for Transcatheter Mitral Valve Interventions SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE catheterization; endovascular procedures; heart valve prosthesis implantation; magnetic resonance imaging, interventional; mitral valve ID EXPANDABLE BIOLOGICAL VALVE; ASSISTED THORACIC-SURGERY; LUNG-CANCER; CARDIAC-CATHETERIZATION; HEART-DISEASE; REPLACEMENT; IMPLANTATION; EXPERIENCE; LOBECTOMY; DIAGNOSIS AB Background-Percutaneous access for mitral interventions is currently limited to transapical and transseptal routes, both of which have shortcomings. We hypothesized that the left atrium could be accessed directly through the posterior chest wall under imaging guidance. Methods and Results-We tested percutaneous transthoracic left atrial access in 12 animals (10 pigs and 2 sheep) under real-time magnetic resonance imaging or x-ray fluoroscopy plus C-arm computed tomographic guidance. The pleural space was insufflated with CO2 to displace the lung, an 18F sheath was delivered to the left atrium, and the left atrial port was closed using an off-the-shelf nitinol cardiac occluder. Animals were survived for a minimum of 7 days. The left atrial was accessed, and the port was closed successfully in 12/12 animals. There was no procedural mortality and only 1 hemodynamically insignificant pericardial effusion was observed at follow-up. We also successfully performed the procedure on 3 human cadavers. A simulated trajectory to the left atrium was present in all of 10 human cardiac computed tomographic angiograms analyzed. Conclusions-Percutaneous transthoracic left atrial access is feasible without instrumenting the left ventricular myocardium. In our experience, magnetic resonance imaging offers superb visualization of anatomic structures with the ability to monitor and address complications in real-time, although x-ray guidance seems feasible. Clinical translation seems realistic based on human cardiac computed tomographic analysis and cadaver testing. This technique could provide a direct nonsurgical access route for future transcatheter mitral implantation. C1 [Rogers, Toby; Ratnayaka, Kanishka; Schenke, William H.; Sonmez, Merdim; Kocaturk, Ozgur; Mazal, Jonathan R.; Chen, Marcus Y.; Faranesh, Anthony Z.; Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Troendle, James F.] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Ratnayaka, Kanishka] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA. [Kocaturk, Ozgur] Bogazici Univ, Inst Biomed Engn, Istanbul, Turkey. [Flugelman, Moshe Y.] Carmel Hosp, Dept Cardiol, Haifa, Israel. RP Lederman, RJ (reprint author), NHLBI, NIH, Bldg 10,Room 2c713, Bethesda, MD 20892 USA. EM lederman@nih.gov OI Rogers, Toby/0000-0002-6043-3137 FU Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health [Z01-HL005062, Z01-HL006040] FX This work was supported by the Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health (Z01-HL005062 and Z01-HL006040). NR 32 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD JUN PY 2015 VL 8 IS 6 AR e002538 DI 10.1161/CIRCINTERVENTIONS.114.002538 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DF4NX UT WOS:000371327100019 PM 26022536 ER PT J AU Doumatey, AP Xu, HC Huang, HX Trivedi, NS Lei, L Elkahloun, A Adeyemo, A Rotimi, CN AF Doumatey, Ayo P. Xu, Huichun Huang, Hanxia Trivedi, Niraj S. Lei, Lin Elkahloun, Abdel Adeyemo, Adebowale Rotimi, Charles N. TI Global Gene Expression Profiling in Omental Adipose Tissue of Morbidly Obese Diabetic African Americans SO JOURNAL OF ENDOCRINOLOGY AND METABOLISM LA English DT Article DE Obesity; Global gene expression; Type 2 diabetes; African Americans ID 3T3-L1 ADIPOCYTES; INSULIN-RESISTANCE; GLUCOSE-TRANSPORT; COMPLICATIONS; TELOMERASE; MICRORNA; GLUT4; RATS; ASSOCIATION; POPULATIONS AB Background: Adipose tissues play an important role in the pathophysiology of obesity-related diseases including type 2 diabetes (T2D). To describe gene expression patterns and functional pathways in obesity-related T2D, we performed global transcript profiling of omental adipose tissue (OAT) in morbidly obese individuals with or without T2D. Methods: Twenty morbidly obese (mean BMI: about 54 kg/m(2)) subjects were studied, including 14 morbidly obese individuals with T2D (cases) and six morbidly obese individuals without T2D (reference group). Gene expression profiling was performed using the Affy-metrix U133 Plus 2.0 human genome expression array. Analysis of covariance was performed to identify differentially expressed genes (DEGs). Bioinformatics tools including PANTHER and Ingenuity Pathway Analysis (IPA) were applied to the DEGs to determine biological functions, networks and canonical pathways that were over-represented in these individuals. Results: At an absolute fold change threshold of 2 and false discovery rate (FDR) of < 0.05, 68 DEGs were identified in cases compared to the reference group. Myosin X (MYO10) and transforming growth factor beta regulator 1 (TBRG1) were upregulated. MYO10 encodes for an actin-based motor protein that has been associated with T2D. Telomere extension by telomerase (HNRNPA1, TNKS2), D-myo-inositol (1,4,5)-trisphosphate biosynthesis (PIP5K1A, PIP4K2A), and regulation of actin-based motility by Rho (ARPC3) were the most significant canonical pathways and overlay with T2D signaling path-way. Upstream regulator analysis predicted five miRNAs (miR-320b, miR-381-3p, miR-3679-3p, miR-494-3p, and miR-141-3p), as regulators of the expression changes identified. Conclusion: This study identified a number of transcripts and miRNAs in OAT as candidate novel players in the pathophysiology of T2D in African Americans. C1 [Doumatey, Ayo P.; Xu, Huichun; Huang, Hanxia; Lei, Lin; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, 12 South Dr Bldg12A-4047, Bethesda, MD 20892 USA. [Trivedi, Niraj S.] NHGRI, Computat & Stat Genom Branch, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel] NHGRI, Core Lab Canc Genet, NIH, Bethesda, MD 20892 USA. [Xu, Huichun] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Doumatey, AP (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, 12 South Dr Bldg12A-4047, Bethesda, MD 20892 USA. EM doumateya@mail.nih.gov; rotimic@mail.nih.gov FU FIC NIH HHS [T37 TW000041]; Intramural NIH HHS [Z99 HG999999]; NHGRI NIH HHS [Z01 HG200362]; NIMHD NIH HHS [P20 MD006899] NR 47 TC 1 Z9 1 U1 0 U2 0 PU ELMER PRESS INC PI QUEBEC PA 9160 BOUL LEDUC, BUREAU 410, BROSSARD, QUEBEC, J4Y 0E3, CANADA SN 1923-2861 EI 1923-287X J9 J ENDOCRINOL METAB JI J. Endocrinol. Metab. PD JUN PY 2015 VL 5 IS 3 BP 199 EP 210 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DE0ZF UT WOS:000370353700001 PM 26504501 ER PT J AU Patel, J Al Rifai, M Blaha, MJ Budoff, MJ Post, WS Polak, JF Bluemke, DA Scheuner, MT Kronmal, RA Blumenthal, RS Nasir, K McEvoy, JW AF Patel, Jaideep Al Rifai, Mahmoud Blaha, Michael J. Budoff, Matthew J. Post, Wendy S. Polak, Joseph F. Bluemke, David A. Scheuner, Maren T. Kronmal, Richard A. Blumenthal, Roger S. Nasir, Khurram McEvoy, John W. TI Coronary Artery Calcium Improves Risk Assessment in Adults With a Family History of Premature Coronary Heart Disease Results From Multiethnic Study of Atherosclerosis SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; carotid intima-media thickness; primary prevention; vascular calcification ID INTIMA-MEDIA THICKNESS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PREVENTION; METAANALYSIS; PREDICTION; EVENTS; HEALTH; MESA AB Background-The prognostic value of coronary artery calcium (CAC) or carotid intima-media thickness (CIMT) among asymptomatic adults with a family history (FH) of premature coronary heart disease is unclear. Methods and Results-Multiethnic Study of Atherosclerosis enrolled 6814 adults without known atherosclerotic cardiovascular disease (ASCVD). Hard ASCVD events were ascertained over a median follow-up of 10.2 years. We estimated adjustedhazard ratios for CAC and CIMT categories using Cox regression, both within and across FH status groups. Improvement in discrimination with CAC or CIMT added to variables from the ASCVD pooled cohort equation was also evaluated using receiver-operating characteristic curve and likelihood ratio analysis. Of 6125 individuals (62 +/- 10 years; 47% men) who reported information on FH, 1262 (21%) had an FH of premature coronary heart disease. Among these, 104 hard ASCVD events occurred. Crude incidence rates (per 1000 person-years) for hard ASCVD were 4.4 for CAC, 0 (n= 574; 46% of the sample); 8.8 for CAC, 1 to 99 (n= 368); 14.9 for CAC, 100 to 399 (n= 178); and 20.8 for CAC, >= 400 (n= 142). Relative to CAC= 0, adjusted hard ASCVD hazard ratios for each CAC category among persons with an FH were 1.64 (95% confidence interval, 0.94-2.87), 2.45 (1.31-4.58), and 2.80 (1.44-5.43), respectively. However, there was no increased adjusted hazard for hard ASCVD in high versus low CIMT categories. In participants with an FH of premature coronary heart disease, CAC improved discrimination of hard ASCVD events (P< 0.001). However, CIMT did not discriminate ASCVD (P= 0.70). Conclusions-Nearly half of individuals reporting FH have zero CAC and may receive less net benefit from aspirin or statin therapy. Among persons with an FH, CAC is a robust marker of absolute and relative risk of ASCVD, whereas CIMT is not. C1 [Patel, Jaideep; Al Rifai, Mahmoud; Blaha, Michael J.; Post, Wendy S.; Blumenthal, Roger S.; Nasir, Khurram; McEvoy, John W.] Johns Hopkins Univ, Dept Med, Div Cardiol, Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA. [Patel, Jaideep] Virginia Commonwealth Univ, Med Ctr, Div Internal Med, Richmond, VA 23284 USA. [Budoff, Matthew J.] Univ Calif Los Angeles, Div Cardiol, Los Angeles Biomed Res Inst Harbor, Torrance, CA USA. [Polak, Joseph F.] Tufts Med Ctr, Dept Radiol Cardiovasc Ctr, Boston, MA USA. [Bluemke, David A.] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Scheuner, Maren T.] Greater Los Angeles Healthcare Syst, Dept Med, Vet Adm, Div Med Genet, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Kronmal, Richard A.] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Nasir, Khurram] Baptist Hlth South Florida, Ctr Healthcare Adv & Outcomes, Miami, FL USA. [Nasir, Khurram] Baptist Hlth South Florida, Miami Cardiac & Vasc Inst, Miami, FL USA. [Nasir, Khurram] Florida Int Univ, Robert Stempel Coll Publ Hlth, Herbert Wertheim Coll Med & Epidemiol, Dept Med, Miami, FL 33199 USA. RP McEvoy, JW (reprint author), Johns Hopkins Sch Med, Div Cardiol, Johns Hopkins Ciccarone Ctr Prevent Heart Dis, 600 N Wolfe St,Carnegie 568, Baltimore, MD 21287 USA. EM jmcevoy1@jhmi.edu OI Patel, Jaideep/0000-0001-5130-7772 FU Pollin Cardiovascular Prevention Fellowship; P.J. Schafer fund for early career investigators FX Dr McEvoy is supported by the Pollin Cardiovascular Prevention Fellowship and the P.J. Schafer fund for early career investigators. Dr Budoff is a consultant for General Electric. The other authors report no conflicts. NR 29 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JUN PY 2015 VL 8 IS 6 AR e003186 DI 10.1161/CIRCIMAGING.115.003186 PG 16 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DD1WT UT WOS:000369714500008 PM 26047825 ER PT J AU Norton, JA Krampitz, G Zemek, A Longacre, T Jensen, RT AF Norton, Jeffrey A. Krampitz, Geoffrey Zemek, Allison Longacre, Teri Jensen, Robert T. TI Better Survival But Changing Causes of Death in Patients With Multiple Endocrine Neoplasia Type 1 SO ANNALS OF SURGERY LA English DT Letter ID NEUROENDOCRINE-TUMORS; GUIDELINES C1 [Norton, Jeffrey A.; Krampitz, Geoffrey] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. [Zemek, Allison; Longacre, Teri] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Jensen, Robert T.] Natl Inst Arthrit Diabet Digest & Kidney Dis, Digest Dis Branch, NIH, Bethesda, MD USA. RP Norton, JA (reprint author), Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. EM janorton@stanford.edu NR 10 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JUN PY 2015 VL 261 IS 6 BP E147 EP E148 DI 10.1097/SLA.0000000000001211 PG 2 WC Surgery SC Surgery GA DD0LN UT WOS:000369611600001 PM 26291955 ER PT J AU Lange, CM Hue, S Violari, A Cotton, M Gibb, D Babiker, A Otwombe, K Panchia, R Dobbels, E Jean-Philippe, P McIntyre, JA Pillay, D Gupta, RK AF Lange, Camille Marie Hue, Stephane Violari, Avy Cotton, Mark Gibb, Diana Babiker, Abdel Otwombe, Kennedy Panchia, Ravindre Dobbels, Els Jean-Philippe, Patrick McIntyre, James A. Pillay, Deenan Gupta, Ravindra Kumar TI Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; resistance; single genome; multiclass drug resistance; children ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; VERTICAL TRANSMISSION; REVERSE-TRANSCRIPTASE; VIROLOGICAL FAILURE; HIV-1; NEVIRAPINE; INFANTS; MULTIPLE; WOMEN AB The WHO recommends protease inhibitor (PI)-based antiretroviral therapy (ART) for vertically infected children after failed nevirapine (NVP) prophylaxis. Emergence of PI resistance on the backdrop of preexisting non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance could compromise long-term treatment options in such children. We characterized multiclass drug resistance using single genome sequencing (SGS) in children with viremia while receiving PI-based ART. We applied SGS of HIV-1 protease (PR) and reverse transcriptase to longitudinal samples from a cohort of the Children with HIV Early Antiretroviral Therapy trial with viral loads >1000 copies per milliliter after 40 weeks of early ART. Bulk sequencing revealed NVP-selected resistance in 50% of these children, whereas SGS revealed NVP-selected resistance in 70%. Two children had baseline NRTI and PI mutations, suggesting previous maternal ART. Linked multiclass drug resistance after PI-based ART was detected by SGS in 2 of 10 children. In one child, the majority species contained M184V in reverse transcriptase linked to L10F, M46I/L, I54V, and V82A in PR and a triple-class drug-resistant variant with these mutations linked to the NNRTI mutation V108I. In the second child, the majority species contained M184V and V82A linked within viral genomes. We conclude that when PI-based ART is initiated soon after birth after single dose-NVP prophylaxis, PI and NRTI resistance can occur in the majority species as expected and also be selected on the same genomes as preexisting NNRTI-resistant mutations. These observations highlight a future therapeutic challenge for vertically infected children where antiretroviral drug classes are limited. C1 [Lange, Camille Marie; Hue, Stephane; Pillay, Deenan; Gupta, Ravindra Kumar] UCL, Div Infect & Immun, London, England. [Violari, Avy; Otwombe, Kennedy; Panchia, Ravindre; Dobbels, Els] Univ Witwatersrand, Perinatal HIV Res Unit, Fac Hlth Sci, ZA-2050 Johannesburg, South Africa. [Cotton, Mark] Univ Stellenbosch, Childrens Infect Dis Clin Res Unit, Fac Med & Hlth Sci, ZA-7505 Tygerberg, South Africa. [Gibb, Diana; Babiker, Abdel] UCL, MRC, Clin Trials Unit, London, England. [Jean-Philippe, Patrick] NIAID, HJF DAIDS, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike, Bethesda, MD 20892 USA. [McIntyre, James A.] Univ Cape Town, Anova Hlth Inst, Sch Publ Hlth & Family Med, ZA-7925 Cape Town, South Africa. [Pillay, Deenan] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, POB 198, Mtubatuba, South Africa. RP Pillay, D (reprint author), Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, POB 198, Mtubatuba, South Africa. EM dpillay@africacentre.ac.za; ravindra.gupta@ucl.ac.uk OI Pillay, Dorsamy/0000-0003-3640-2573 FU University College London Grand Challenges Global Health Program; US National Institutes of Health; Abbvie Laboratories; Wellcome Trust Fellowship [WT093722MA]; National Institute of Allergy and Infectious Diseases of the US National Institutes for Health, through the Comprehensive International Program of Research on AIDS network [U19 AI53217]; Departments of Health of the Western Cape Province, South Africa; Departments of Health of the Gauteng Province, South Africa; GlaxoSmithKline FX Supported by University College London Grand Challenges Global Health Program, US National Institutes of Health, and Abbvie Laboratories. R.K.G. is funded by a Wellcome Trust Fellowship (WT093722MA). Funding for the CHER study was provided by the National Institute of Allergy and Infectious Diseases of the US National Institutes for Health, through the Comprehensive International Program of Research on AIDS network (Grant number U19 AI53217). Additional support was provided by the Departments of Health of the Western Cape and Gauteng Provinces, South Africa, and GlaxoSmithKline. NR 26 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN 1 PY 2015 VL 69 IS 2 BP 138 EP 144 DI 10.1097/QAI.0000000000000568 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DC5GW UT WOS:000369250500009 PM 25923117 ER PT J AU Zidar, DA Juchnowski, S Ferrari, B Clagett, B Pilch-Cooper, HA Rose, S Rodriguez, B McComsey, GA Sieg, SF Mehta, NN Lederman, MM Funderburg, NT AF Zidar, David A. Juchnowski, Steven Ferrari, Brian Clagett, Brian Pilch-Cooper, Heather A. Rose, Shawn Rodriguez, Benigno McComsey, Grace A. Sieg, Scott F. Mehta, Nehal N. Lederman, Michael M. Funderburg, Nicholas T. TI Oxidized LDL Levels Are Increased in HIV Infection and May Drive Monocyte Activation SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT AIDS-Clinical-Trials-Group Meeting on End Organ Disease and Inflammation TSG Think Tank CY JUL 31, 2013 CL Washington, DC SP AIDS Clin Trials Grp DE HIV; monocytes; oxidized LDL; tissue factor ID HUMAN-IMMUNODEFICIENCY-VIRUS; TISSUE FACTOR EXPRESSION; ACUTE CORONARY SYNDROMES; ACTIVE ANTIRETROVIRAL THERAPY; ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; CARDIOVASCULAR RISK; VENOUS THROMBOEMBOLISM; STERILE INFLAMMATION; DISEASE PROGRESSION AB Background: HIV infection is associated with increased cardiovascular risk, and this risk correlates with markers of monocyte activation. We have shown that HIV is associated with a prothrombotic monocyte phenotype, which can be partially mitigated by statin therapy. We therefore explored the relationship between oxidized low-density lipoprotein (oxLDL) particles and monocyte activation. Methods: We performed phenotypic analysis of monocytes using flow cytometry on fresh whole blood in 54 patients with HIV and 24 controls without HIV. Plasma levels of oxLDL, soluble CD14, IL-6, and soluble CD163 were measured by enzyme-linked immunosorbent assay. In vitro experiments were performed using flow cytometry. Results: Plasma levels of oxLDL were significantly increased in HIV infection compared with controls (60.1 units vs. 32.1 units, P < 0.001). Monocyte expression of the oxLDL receptors, CD36 and Toll-like receptor 4, was also increased in HIV. OxLDL levels correlated with markers of monocyte activation, including soluble CD14, tissue factor expression on inflammatory monocytes, and CD36. In vitro stimulation with oxLDL, but not to low-density lipoprotein, resulted in expansion of inflammatory monocytes and increased monocyte expression of tissue factor, recapitulating the monocyte profile we find in HIV disease. Conclusions: OxLDL may contribute to monocyte activation, and further study in the context of HIV disease is warranted. C1 [Zidar, David A.; Juchnowski, Steven] Univ Hosp Case Med Ctr, Harrington Heart & Vasc Inst, Cleveland, OH USA. [Ferrari, Brian; Clagett, Brian; Pilch-Cooper, Heather A.; Rodriguez, Benigno; McComsey, Grace A.; Sieg, Scott F.; Lederman, Michael M.] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Med, Cleveland, OH 44106 USA. [Rose, Shawn; Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bldg 10, Bethesda, MD 20892 USA. [Rose, Shawn] NIAMSD, Bethesda, MD 20892 USA. [McComsey, Grace A.] Rainbow Babies & Childrens Hosp, 2101 Adelbert Rd, Cleveland, OH 44106 USA. [Funderburg, Nicholas T.] Ohio State Univ, Sch Hlth & Rehabil Sci, Columbus, OH 43210 USA. RP Funderburg, NT (reprint author), 453 W 10th Ave,535A Atwell Hall, Columbus, OH 43210 USA. EM Nicholas.funderburg@osumc.edu RI Funderburg, Nicholas/L-8022-2013 FU NCATS NIH HHS [KL2 TR000440, KL2TR000440]; NHLBI NIH HHS [1K99HL108743-01, K99 HL108743, R00 HL108743, R00HL108743, R56 HL126563, R56HL126563]; NIAID NIH HHS [AI-07164, AI-36219, AI-67039, AI-68636, P30 AI036219, R24 AI067039, U01 AI068636, UM1 AI068636] NR 50 TC 19 Z9 19 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN 1 PY 2015 VL 69 IS 2 BP 154 EP 160 DI 10.1097/QAI.0000000000000566 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DC5GW UT WOS:000369250500011 PM 25647528 ER PT J AU Himes, SK Huo, YL Siberry, GK Williams, PL Rice, ML Sirois, PA Frederick, T Hazra, R Huestis, MA AF Himes, Sarah K. Huo, Yanling Siberry, George K. Williams, Paige L. Rice, Mabel L. Sirois, Patricia A. Frederick, Toni Hazra, Rohan Huestis, Marilyn A. CA Pediatric HIV AIDS Cohort Study PH TI Meconium Atazanavir Concentrations and Early Language Outcomes in HIV-Exposed Uninfected Infants With Prenatal Atazanavir Exposure SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE meconium; atazanavir; antiretroviral; language; HIV-exposed uninfected infants ID SINGLE-DOSE NEVIRAPINE; SERUM BILIRUBIN LEVELS; HUMAN-LIVER; IN-UTERO; NEONATAL HYPERBILIRUBINEMIA; DRUG EXPOSURE; EXPRESSION; PREGNANCY; CYP3A7; TRANSMISSION AB Objective: To investigate whether prenatal atazanavir (ATV) exposure, assessed by meconium antiretroviral (ARV) quantification, predicts early child language outcomes. Prenatal ATV exposure previously was associated with poorer language development in 1-year olds. Methods: Pregnant women with HIV and their uninfected infants enrolled in the Surveillance Monitoring of Antiretroviral Therapy Toxicities study. Meconium ARV concentrations were quantified by liquid chromatography-tandem mass spectrometry. Language development at 1 year was assessed with MacArthur-Bates Communicative Development Inventory (CDI) and Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Late language emergence was defined as >= 1 of 4 CDI scores <= 10th percentile for age. Associations between fetal ATV exposure timing and duration, meconium ATV concentration, and language outcomes were evaluated, adjusting for potential confounders. Results: Through 2013, meconium samples were available from 175 of 432 infants with prenatal ATV exposure. Valid Bayley-III (n = 93) and CDI (n = 106) assessments also were available. After adjustment for potential confounders, higher ATV meconium concentrations were associated with lower late language emergence risk (P = 0.04) and cumulative ATV exposure duration also was associated with higher Bayley-III Language scores (P = 0.03). Maternal ATV duration and initiation week correlated with ATV meconium concentrations (positively and negatively, respectively). Conclusions: Higher meconium ATV concentrations were protective against developmental language delays at 1 year, suggesting the importance of fetal ATV detoxification into meconium. This information supports ATV exposure safety for infant language development. ATV is a preferred ARV for pregnant women with HIV, suggesting the importance of ATV safety investigations. Additionally, further pursuit of the influences on language development in HIV-exposed uninfected infants is required. C1 [Himes, Sarah K.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. [Huo, Yanling; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 665 Huntington Ave, Boston, MA 02115 USA. [Siberry, George K.; Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA. [Rice, Mabel L.] Univ Kansas, Speech, Language, Hearing Dept, Lawrence, KS 66045 USA. [Sirois, Patricia A.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. [Frederick, Toni] Keck Sch Med USC, Dept Res Pediat, Maternal Child & Adolescent Program Infect Dis &, Los Angeles, CA USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov OI Rice, Mabel/0000-0002-8150-5523 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Allergy and Infectious Diseases; Office of AIDS Research; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Heart Lung and Blood Institute; National Institute of Dental and Craniofacial Research; National Institute on Alcohol Abuse and Alcoholism; Harvard University School of Public Health [HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3]; Tulane University School of Medicine [HD052104, 3U01HD052104-06S1] FX The Pediatric HIV/AIDS Cohort Study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard University School of Public Health (HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3) (Principal Investigator: George Seage; Project Director: Julie Alperen) and the Tulane University School of Medicine (HD052104, 3U01HD052104-06S1) (Principal Investigator: Russell Van Dyke; Co-principal Investigator: Kenneth Rich; Project Director: Patrick Davis). NR 43 TC 1 Z9 1 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN 1 PY 2015 VL 69 IS 2 BP 178 EP 186 DI 10.1097/QAI.0000000000000558 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DC5GW UT WOS:000369250500014 PM 26009830 ER PT J AU Grobman, WA Bailit, JL Rice, MM Wapner, RJ Reddy, UM Varner, MW Thorp, JM Leveno, KJ Caritis, SN Iams, JD Tita, ATN Saade, G Rouse, DJ Blackwell, SC Tolosa, JE VanDorsten, JP AF Grobman, William A. Bailit, Jennifer L. Rice, Madeline Murguia Wapner, Ronald J. Reddy, Uma M. Varner, Michael W. Thorp, John M., Jr. Leveno, Kenneth J. Caritis, Steve N. Iams, Jay D. Tita, Alan T. N. Saade, George Rouse, Dwight J. Blackwell, Sean C. Tolosa, Jorge E. VanDorsten, J. Peter CA Eunice Kennedy Shriver Natl Inst C TI Racial and Ethnic Disparities in Maternal Morbidity and Obstetric Care SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID POSTPARTUM HEMORRHAGE; VAGINAL DELIVERY; SEVERE PERINEAL; WOMEN; LACERATIONS; MORTALITY; RISK AB OBJECTIVE: To evaluate whether racial and ethnic disparities exist in obstetric care and adverse outcomes. METHODS: We analyzed data from a cohort of women who delivered at 25 hospitals across the United States over a 3-year period. Race and ethnicity was categorized as non-Hispanic white, non-Hispanic black, Hispanic, or Asian. Associations between race and ethnicity and severe postpartum hemorrhage, peripartum infection, and severe perineal laceration at spontaneous vaginal delivery as well as between race and ethnicity and obstetric care (eg, episiotomy) relevant to the adverse outcomes were estimated by univariable analysis and multivariable logistic regression. RESULTS: Of 115,502 studied women, 95% were classified by one of the race and ethnicity categories. Non-Hispanic white women were significantly less likely to experience severe postpartum hemorrhage (1.6% non-Hispanic white compared with 3.0% non-Hispanic black compared with 3.1% Hispanic compared with 2.2% Asian) and peripartum infection (4.1% non-Hispanic white compared with 4.9% non-Hispanic black compared with 6.4% Hispanic compared with 6.2% Asian) than others (P<.001 for both). Severe perineal laceration at spontaneous vaginal delivery was significantly more likely in Asian women (2.5% non-Hispanic white compared with 1.2% non-Hispanic black compared with 1.5% Hispanic compared with 5.5% Asian; P<.001). These disparities persisted in multivariable analysis. Many types of obstetric care examined also were significantly different according to race and ethnicity in both univariable and multivariable analysis. There were no significant interactions between race and ethnicity and hospital of delivery. CONCLUSION: Racial and ethnic disparities exist for multiple adverse obstetric outcomes and types of obstetric care and do not appear to be explained by differences in patient characteristics or by delivery hospital. C1 Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA. Northwestern Univ, Dept Gynecol, Chicago, IL 60611 USA. Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. Columbia Univ, New York, NY USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Pittsburgh, Pittsburgh, PA USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Texas Med Branch, Galveston, TX 77555 USA. Brown Univ, Providence, RI 02912 USA. Univ Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Houston, TX 77030 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Med Univ S Carolina, Charleston, SC 29425 USA. George Washington Univ, Biostat Ctr, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Grobman, WA (reprint author), Northwestern Univ, Sch Med, Maternal Fetal Med, 250 East Super St,Suite 05-2175, Chicago, IL 60611 USA. EM w-grobman@northwestern.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD21410, HD27869, HD27915, HD27917, HD34116, HD34208, HD36801, HD40500, HD40512, HD40544, HD40545, HD40560, HD40485, HD53097, HD53118]; National Center for Research Resources [UL1 RR024989, 5UL1 RR025764] FX The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD21410, HD27869, HD27915, HD27917, HD34116, HD34208, HD36801, HD40500, HD40512, HD40544, HD40545, HD40560, HD40485, HD53097, HD53118) and the National Center for Research Resources (UL1 RR024989; 5UL1 RR025764). NR 20 TC 11 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2015 VL 125 IS 6 BP 1460 EP 1467 DI 10.1097/AOG.0000000000000735 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DD0VA UT WOS:000369637100026 PM 26000518 ER PT J AU Zhang, J Troendle, J Grantz, KL Reddy, UM AF Zhang, Jun Troendle, James Grantz, Katherine L. Reddy, Uma M. TI Statistical aspects of modeling the labor curve SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE deceleration phase; Friedman curve; labor curve; modeling; partogram ID GRAPHICOSTATISTICAL ANALYSIS AB In a recent review by Cohen and Friedman, several statistical questions on modeling labor curves were raised. This article illustrates that asking data to fit a preconceived model or letting a sufficiently flexible model fit observed data is the main difference in principles of statistical modeling between the original Friedman curve and our average labor curve. An evidence-based approach to construct a labor curve and establish normal values should allow the statistical model to fit observed data. In addition, the presence of the deceleration phase in the active phase of an average labor curve was questioned. Forcing a deceleration phase to be part of the labor curve may have artificially raised the speed of progression in the active phase with a particularly large impact on earlier labor between 4 and 6 cm. Finally, any labor curve is illustrative and may not be instructive in managing labor because of variations in individual labor pattern and large errors in measuring cervical dilation. With the tools commonly available, it may be more productive to establish a new partogram that takes the physiology of labor and contemporary obstetric population into account. C1 [Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai 200030, Peoples R China. [Troendle, James] NHLBI, NIH, Bethesda, MD USA. [Grantz, Katherine L.; Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Zhang, J (reprint author), Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai 200030, Peoples R China. EM junjimzhang@gmail.com OI Grantz, Katherine/0000-0003-0276-8534 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This study was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 15 TC 0 Z9 0 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 2015 VL 212 IS 6 BP 750 EP 753 AR 750.e1 DI 10.1016/j.ajog.2015.04.014 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CJ1RN UT WOS:000355262000010 PM 25891997 ER PT J AU Althabe, F Belizan, JM McClure, EM Hemingway-Foday, J Berrueta, M Mazzoni, A Ciganda, A Goudar, SS Kodkany, BS Mahantshetti, NS Dhaded, SM Katageri, GM Metgud, MC Joshi, AM Bellad, MB Honnungar, NV Derman, RJ Saleem, S Pasha, O Ali, S Hasnain, F Goldenberg, RL Esamai, F Nyongesa, P Ayunga, S Liechty, EA Garces, AL Figueroa, L Hambidge, KM Krebs, NF Patel, A Bhandarkar, A Waikar, M Hibberd, PL Chomba, E Carlo, WA Mwiche, A Chiwila, M Manasyan, A Pineda, S Meleth, S Thorsten, V Stolka, K Wallace, DD Koso-Thomas, M Jobe, AH Buekens, PM AF Althabe, Fernando Belizan, Jose M. McClure, Elizabeth M. Hemingway-Foday, Jennifer Berrueta, Mabel Mazzoni, Agustina Ciganda, Alvaro Goudar, Shivaprasad S. Kodkany, Bhalachandra S. Mahantshetti, Niranjana S. Dhaded, Sangappa M. Katageri, Geetanjali M. Metgud, Mrityunjay C. Joshi, Anjali M. Bellad, Mrutyunjaya B. Honnungar, Narayan, V Derman, Richard J. Saleem, Sarah Pasha, Omrana Ali, Sumera Hasnain, Farid Goldenberg, Robert L. Esamai, Fabian Nyongesa, Paul Ayunga, Silas Liechty, Edward A. Garces, Ana L. Figueroa, Lester Hambidge, K. Michael Krebs, Nancy F. Patel, Archana Bhandarkar, Anjali Waikar, Manjushri Hibberd, Patricia L. Chomba, Elwyn Carlo, Waldemar A. Mwiche, Angel Chiwila, Melody Manasyan, Albert Pineda, Sayury Meleth, Sreelatha Thorsten, Vanessa Stolka, Kristen Wallace, Dennis D. Koso-Thomas, Marion Jobe, Alan H. Buekens, Pierre M. TI A Population-Based, Multifaceted Strategy to Implement Antenatal Corticosteroid Treatment Versus Standard Care for the Reduction of Neonatal Mortality Due to Preterm Birth in Low-Income and Middle-Income Countries: The ACT Cluster Randomized Trial SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Antenatal corticosteroids are 1 of the most effective hospital-based treatments to reduce neonatal mortality for pregnant women at risk of preterm birth. While studies have shown reductions in neonatal mortality in high-and middle-income countries, and the treatment has been recommended by national and international health organizations, less than 10% of women in low-income countries at risk of preterm birth receive antenatal corticosteroids. This cluster-randomized trial aimed to assess the feasibility, safety, and effectiveness of a multifaceted intervention to increase the use of these treatments in middle-and low-income countries. Between October 2011 and March 2014, this trial randomly assigned (1: 1) clusters in rural and semiurban areas in Guatemala, Argentina, India, Kenya, Pakistan, and Zambia to this intervention or to standard care. To be eligible, clusters had to have at least 300 births annually in the defined area, either at homes or in facilities. Part of the intervention included better identification of women at risk of preterm birth. In intervention clusters, all health care providers were trained to identify women at risk of preterm birth and to administer dexamethasone in 1 course of four 6-mg doses every 12 hours to at risk women at less than 36 weeks' gestational age. In the intervention arm, women identified as high risk of preterm birth were also referred, but transportation was not provided. All clusters were training in newborn care. There were 51 intervention clusters with 2520 live births less than the fifth percentile for birth weight and 50 control clusters with 2258 in that percentile. In the intervention cluster, 45% of women received antenatal corticosteroids, whereas 10% of the control group received them (P < 0.0001). Of the less-than-fifth-percentile infants in the intervention group, 28-day neonatal mortality was 225 per 1000 live births, compared with a 323-per-1000-live-births neonatal mortality rate in that percentile in the control group (relative risk (RR), 0.96; 95% confidence interval [CI], 0.87-1.06; P = 0.65). Stillbirths occurred in 229 per 1000 births in the intervention group and 247 per 1000 births in the control group (RR, 0.99; 95% CI, 0.90-1.09; P = 0.81). Including all pregnancies, the neonatal mortality rate for the intervention group was 27.4 per 1000 and 23.9 per 1000 for the control group (RR, 1.12; 95% CI, 1.02-1.22; P = 0.0127), and the stillbirth rate in the intervention group was 26.8 per 1000, and that rate was 24.3 per 1000 in the control group (RR, 1.11; 95% CI, 1.02-1.22; P = 0.0181). Researchers found that the intervention group was overtreated with antenatal corticosteroids, and even though nearly half of women delivering less-than-fifth-percentile infants received steroids, neonatal mortality did not decrease. Neonatal deaths were significantly increased in the intervention group (3.5 per 1000 live births), as were perinatal deaths (5.1 per 1000 live births) and maternal infection (3%-6% increase). The authors of the study advise caution in implementing interventions such as this one. The findings do not support this strategy, and whether the antenatal corticosteroids directly caused the unfavorable results in the intervention group should be further explored. C1 [Althabe, Fernando; Belizan, Jose M.; Berrueta, Mabel; Mazzoni, Agustina; Ciganda, Alvaro] Inst Clin Effectiveness & Hlth Policy IECS, Buenos Aires, DF, Argentina. [Ciganda, Alvaro] UNICEM, Montevideo, Uruguay. [McClure, Elizabeth M.; Hemingway-Foday, Jennifer; Meleth, Sreelatha; Thorsten, Vanessa; Stolka, Kristen; Wallace, Dennis D.] RTI Int, Durham, NC USA. [Goudar, Shivaprasad S.; Kodkany, Bhalachandra S.; Mahantshetti, Niranjana S.; Dhaded, Sangappa M.; Metgud, Mrityunjay C.; Joshi, Anjali M.; Bellad, Mrutyunjaya B.; Honnungar, Narayan, V] KLE Univ, Jawaharlal Nehru Med Coll, Womens & Childrens Hlth Res Unit, Belgaum, Karnataka, India. [Katageri, Geetanjali M.] S Nijalingappa Med Coll, Bagalkot, Karnataka, India. [Derman, Richard J.] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA. [Saleem, Sarah; Pasha, Omrana; Ali, Sumera; Hasnain, Farid] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan. [Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Esamai, Fabian; Nyongesa, Paul; Ayunga, Silas] Moi Univ, Sch Med, Eldoret, Kenya. [Liechty, Edward A.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Garces, Ana L.; Figueroa, Lester; Pineda, Sayury] Ctr Amer & Panama, Fdn Alimentac & Nutr, Guatemala City, Guatemala. [Garces, Ana L.] Francisco Marroquin Univ, Guatemala City, Guatemala. [Hambidge, K. Michael; Krebs, Nancy F.] Univ Colorado, Sch Med, Denver, CO USA. [Patel, Archana; Bhandarkar, Anjali; Waikar, Manjushri] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chomba, Elwyn; Mwiche, Angel] Univ Teaching Hosp, Lusaka, Zambia. [Carlo, Waldemar A.; Mwiche, Angel] Univ Alabama Birmingham, Birmingham, AL USA. [Chiwila, Melody] Ctr Infect Dis Zambia, Lusaka, Zambia. [Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Jobe, Alan H.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Buekens, Pierre M.] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA. RP Althabe, F (reprint author), Inst Clin Effectiveness & Hlth Policy IECS, Buenos Aires, DF, Argentina. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JUN PY 2015 VL 70 IS 6 BP 379 EP U90 DI 10.1097/01.ogx.0000467226.29492.11 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DC2UT UT WOS:000369073600006 ER PT J AU Moore, HCF Unger, JM Phillips, KA Boyle, F Hitre, E Porter, D Francis, PA Goldstein, LJ Gomez, HL Vallejos, CS Partridge, AH Dakhil, SR Garcia, AA Gralow, J Lombard, JM Forbe, JF Martino, S Barlow, WE Fabian, CJ Minasian, L Meyskens, FL Gelber, RD Hortobagyi, GN Albain, KS AF Moore, Halle C. F. Unger, Joseph M. Phillips, Kelly-Anne Boyle, Frances Hitre, Erika Porter, David Francis, Prudence A. Goldstein, Lori J. Gomez, Henry L. Vallejos, Carlos S. Partridge, Ann H. Dakhil, Shaker R. Garcia, Agustin A. Gralow, Julie Lombard, Janine M. Forbe, John F. Martino, Silvana Barlow, William E. Fabian, Carol J. Minasian, Lori Meyskens, Frank L., Jr. Gelber, Richard D. Hortobagyi, Gabriel N. Albain, Kathy S. CA POEMS S0230 Investigators TI Goserelin for Ovarian Protection During Breast-Cancer Adjuvant Chemotherapy SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Premature ovarian failure is a devastating long-term toxic effect of chemotherapy for premenopausal women. The survival benefit of adjuvant chemotherapy in young women with operable hormone receptor-negative breast cancer is well known, but concern over becoming infertile may influence the choice of treatment for many women. A number of trials have investigated the combined use of a gonadotropin-releasing hormone (GnRH) agonist and adjuvant chemotherapy in an attempt to protect ovarian function in premenopausal women. Results of such studies were mixed, and there were few data on pregnancy outcomes. The aim of this randomized trial was to determine whether administration of the GnRH agonist goserelin with chemotherapy would reduce the rate of ovarian failure after adjuvant or neoadjuvant treatment of hormone-receptor-negative early-stage breast cancer. A total of 257 premenopausal women with operable hormone receptor-negative breast cancer were randomized to receive standard chemotherapy with goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The rate of ovarian failure at 2 years was the primary study end point. Ovarian failure was defined as the absence of menses for the preceding 6 months and follicle-stimulating hormone levels in the postmenopausal range at 2 years. Conditional logistic regression was used to compare rates. Secondary end points evaluated included pregnancy outcomes and disease-free and overall survival. Of the 257 patients, 218 were eligible and could be evaluated: 113 in the chemotherapy-alone group and 105 in the goserelin group. Complete primary end-point data were available for 135 of the 218 patients who could be evaluated. Among these, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group; the odds ratio was 0.30, with a 95% confidence interval of 0.09 to 0.97; 2-sided P = 0.04. To determine the effect of the missing primary end-point data on the main study findings, sensitivity analyses were performed. The results of these analyses showed that the missing data had no significant effect on the association between treatment and stratification variables (age and planned chemotherapy regimen). Among the 218 patients who could be evaluated, more women became pregnant in the goserelin group than in the chemotherapy-alone group (21% vs 11%, P = 0.03). Kaplan-Meier curves showed that more women in the goserelin group had improved disease-free survival (P = 0.04) and overall survival (P = 0.05). Consistent with the findings of previous randomized trials, these data suggest that administration of a GnRH agonist with chemotherapy protects ovarian function, reducing the risk of early menopause and improving prospects for fertility. Although missing primary-end-point data weaken interpretation of the findings, there is no evidence that the missing data influenced the relative comparison between randomized groups. C1 [Moore, Halle C. F.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Unger, Joseph M.; Barlow, William E.] Fred Hutchinson Canc Res Ctr, SWOG Canc Res Grp Stat Ctr, Seattle, WA 98104 USA. [Gralow, Julie] Seattle Canc Care Alliance, Seattle, WA USA. [Gralow, Julie] Univ Washington, Seattle, WA 98195 USA. [Phillips, Kelly-Anne; Francis, Prudence A.] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Phillips, Kelly-Anne; Francis, Prudence A.; Forbe, John F.] Australia & New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. [Boyle, Frances; Lombard, Janine M.; Forbe, John F.] Calvary Mater Hosp, Newcastle, NSW, Australia. [Boyle, Frances] Univ Sydney, Sydney, NSW 2006, Australia. [Phillips, Kelly-Anne; Francis, Prudence A.] Int Breast Canc Study Grp, Bern, Switzerland. [Hitre, Erika] Natl Inst Oncol, Budapest, Hungary. [Porter, David] Auckland Reg Canc & Blood Serv, Auckland, New Zealand. [Goldstein, Lori J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Gomez, Henry L.] Inst Enfermedades Neoplas, Lima, Peru. [Vallejos, Carlos S.] Oncosalud SAC, Lima, Peru. [Partridge, Ann H.; Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gelber, Richard D.] IBCSG Stat Ctr, Boston, MA USA. [Dakhil, Shaker R.] Wichita Community Clin Oncol Program, Wichita, KS USA. [Fabian, Carol J.] Univ Kansas, Westwood, KS USA. [Garcia, Agustin A.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. [Martino, Silvana] Angeles Clin & Res Inst, Santa Monica, CA USA. [Meyskens, Frank L., Jr.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. [Minasian, Lori] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Albain, Kathy S.] Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Moore, HCF (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. OI Gomez, Henry/0000-0003-2660-1843 NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JUN PY 2015 VL 70 IS 6 BP 392 EP 393 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DC2UT UT WOS:000369073600013 ER PT J AU Newman, KA AF Newman, Kam A. TI Commentary on "Back to Anatomy: Improving Landmarking Accuracy of Clinical Procedures Using a Novel Approach to Procedural Teaching'' SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID BONE-MARROW BIOPSY C1 [Newman, Kam A.] NIH, 10 Ctr Dr,Room 6N216, Bethesda, MD 20892 USA. RP Newman, KA (reprint author), NIH, 10 Ctr Dr,Room 6N216, Bethesda, MD 20892 USA. EM Kam.Newman@NIH.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD JUN PY 2015 VL 108 IS 6 BP 318 EP 319 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DC2XL UT WOS:000369082000005 PM 26079454 ER PT J AU Anderson, M Lepene, B Ohayon, J Kashanchi, F Jacobson, S AF Anderson, Monique Lepene, Benjamin Ohayon, Joan Kashanchi, Fatah Jacobson, Steven TI Detection of Human T-cell Lymphotropic Virus Type I proteins in exosomes from HAM/TSP patient CSF by novel nanotrap technology SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Anderson, Monique; Ohayon, Joan; Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Lepene, Benjamin] Ceres Nanosci, Manassas, VA USA. [Kashanchi, Fatah] George Mason Univ, Natl Ctr Biodef & Infect Dis, Fairfax, VA 22030 USA. EM andersonmr2@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P4 BP S2 EP S2 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400005 ER PT J AU Billioux, BJ Massoud, R Ohayon, J Cortese, I Ratner, L Caruso, B Johnson, KR Enose-Akahata, Y Jacobson, S AF Billioux, Bridgette Jeanne Massoud, Raya Ohayon, Joan Cortese, Irene Ratner, Lee Caruso, Breanna Johnson, Kory R. Enose-Akahata, Yoshimi Jacobson, Steven TI Pilot Study of Raltegravir, an Integrase Inhibitor, in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Billioux, Bridgette Jeanne; Massoud, Raya; Ohayon, Joan; Cortese, Irene; Caruso, Breanna; Johnson, Kory R.; Enose-Akahata, Yoshimi; Jacobson, Steven] NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. [Ratner, Lee] Washington Univ, Sch Med, Internal Med Oncol Dept, St Louis, MO USA. EM bridgette.billioux@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P17 BP S8 EP S8 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400018 ER PT J AU Billioux, BJ Jacobson, S AF Billioux, Bridgette Jeanne Jacobson, Steven TI Quantitative Detection of Human Herpesvirus-6 with Digital Droplet PCR in a Patient with Post-Transplant HHV-6 Encephalitis SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Billioux, Bridgette Jeanne; Jacobson, Steven] NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. EM bridgette.billioux@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P16 BP S7 EP S8 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400017 ER PT J AU Ginwala, R Charlins, P Caruso, B Akkina, R Sagar, D Jacobson, S Khan, ZK Jain, P AF Ginwala, Rashida Charlins, Paige Caruso, Breanna Akkina, Ramesh Sagar, Divya Jacobson, Steven Khan, Zafar K. Jain, Pooja TI HTLV-1 infection and neuropathogenesis in the context of Rag1-/-gamma c-/- (RAG1) mice SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Ginwala, Rashida; Sagar, Divya; Khan, Zafar K.; Jain, Pooja] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Sacramento, CA USA. [Ginwala, Rashida; Sagar, Divya; Khan, Zafar K.; Jain, Pooja] Drexel Univ, Coll Med, Inst Mol Med & Infect Dis, Sacramento, CA USA. [Charlins, Paige; Akkina, Ramesh] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Caruso, Breanna; Jacobson, Steven] Natl Inst Hlth, Viral Immunol Sect, Neuroimmunol Branch, New York, NY USA. EM Zafar.Khan@DrexelMed.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P52 BP S24 EP S24 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400053 ER PT J AU Henderson, L Li, WX Tyagi, R Nath, A AF Henderson, Lisa Li, Wenxue Tyagi, Richa Nath, Avindra TI TAR DNA binding protein 43 (TDP-43) enhances HIV replication in macrophages SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Henderson, Lisa; Li, Wenxue; Tyagi, Richa; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. EM lisa.henderson@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P59 BP S27 EP S27 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400060 ER PT J AU Kashanchi, F Sampey, G Iordanskiy, S Saifuddin, M Barklay, R Punya, S Chung, MC Hakami, R Zadeh, M Lepene, B Klase, Z El-Hage, N AF Kashanchi, Fatah Sampey, Gavin Iordanskiy, Sergey Saifuddin, Mohammed Barklay, Robert Punya, Shreya Chung, Myung-Chul Hakami, Ramin Zadeh, Mohammad Lepene, Benjamin Klase, Zachary El-Hage, Nazira TI Exosomes from HIV-1 Infected Cells Stimulate Production of Pro-inflammatory Cytokines through TAR RNA SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Kashanchi, Fatah; Sampey, Gavin; Iordanskiy, Sergey; Saifuddin, Mohammed; Barklay, Robert; Punya, Shreya; Chung, Myung-Chul; Hakami, Ramin; Zadeh, Mohammad] George Mason Univ, Natl Ctr Biodefense & Infect Dis, Fairfax, VA 22030 USA. [Lepene, Benjamin] Ceres Nanosci Inc, Manassas, VA USA. [Klase, Zachary] NIAID, Lab Mol Microbiol, Bethesda, MD USA. [El-Hage, Nazira] Herbert Wertheim Coll Med, Dept Immunol, Miami, FL USA. EM fkashanc@gmu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P70 BP S32 EP S33 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400071 ER PT J AU Li, GH Major, E Nath, A AF Li, Guan-Han Major, Eugene Nath, Avindra TI Restriction of HIV entry into astrocytes is overcome by cell-to-cell contact SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Li, Guan-Han; Major, Eugene; Nath, Avindra] NINDS, NIH, Bethesda, MD 20892 USA. EM guanhan.li@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P84 BP S39 EP S39 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400085 ER PT J AU Li, WX Tyagi, R Henderson, L Li, GH Nath, A AF Li, Wenxue Tyagi, Richa Henderson, Lisa Li, Guanhan Nath, Avindra TI Suicidal gene mediated latent HIV-1 elimination SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Li, Wenxue; Tyagi, Richa; Henderson, Lisa; Li, Guanhan; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. EM wenxue.li@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P85 BP S39 EP S40 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400086 ER PT J AU Liu, FM Dai, S Napoli, A Feng, DC Zhang, YG Hayat, U Peng, X Gordon, J Li, SX Hu, WH Gao, B Khalili, K Qin, XB AF Liu, Fengming Dai, Shen Napoli, Alessandro Feng, Dechun Zhang, Yonggang Hayat, Umar Peng, Xiao Gordon, Jennifer Li, Shuxin Hu, Wenhui Gao, Bin Khalili, Kamel Qin, Xuebin TI Epileptic seizures are induced by intracerebral ablation of astrocytes in the brain, a novel model for dissecting the interaction of neurons with glial cells SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Liu, Fengming; Dai, Shen; Napoli, Alessandro; Zhang, Yonggang; Peng, Xiao; Gordon, Jennifer; Hu, Wenhui; Khalili, Kamel; Qin, Xuebin] Temple Univ, Sch Med, Dept Neurosci, Philadelphia, PA 19122 USA. [Feng, Dechun; Gao, Bin] NIAAA, Lab Liver Dis, Rockville, MD USA. [Hayat, Umar; Li, Shuxin] Temple Univ, Sch Med, Shriners Hosp, Pediat Res Ctr, Philadelphia, PA 19122 USA. EM tuf39759@temple.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P90 BP S41 EP S42 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400091 ER PT J AU Liu, FM Ohtake, Y Fung, DC Dai, S Peng, X Gao, B Li, SX Qin, XB AF Liu, Fengming Ohtake, Yosuke Fung, Dechun Dai, Shen Peng, Xiao Gao, Bin Li, Shuxin Qin, Xuebin TI Application of a novel cell ablation for dissecting the role of immune cells in the pathogenesis of experimental allergic encephalomyelitis SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Liu, Fengming; Dai, Shen; Peng, Xiao; Qin, Xuebin] Temple Univ, Sch Med, Dept Neurosci, Philadelphia, PA 19122 USA. [Ohtake, Yosuke; Li, Shuxin] Temple Univ, Sch Med, Shriners Hosp, Pediat Res Ctr, Philadelphia, PA 19122 USA. [Fung, Dechun; Gao, Bin] NIAAA, Lab Liver Dis, Rockville, MD USA. EM fengming.liu@temple.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P89 BP S41 EP S41 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400090 ER PT J AU Rojas, C Figuera-Losada, M Barnaeva, E Stathis, M Dorskind, JM Thomas, AG Bandaru, VV Yoo, SW McArthur, JC Ferrer, M Haughey, NJ Slusher, BS AF Rojas, Camilo Figuera-Losada, Mariana Barnaeva, Elena Stathis, Marigo Dorskind, Joelle M. Thomas, Ajit G. Bandaru, Veera V. Yoo, Seung-Wan McArthur, Justin C. Ferrer, Marc Haughey, Norman J. Slusher, Barbara S. TI Cambinol, a novel inhibitor of neutral sphingomyelinase 2 shows neuroprotective properties SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 13th International Symposium on NeuroVirology CY JUN 02-06, 2015 CL San Diego, CA C1 [Rojas, Camilo] Johns Hopkins Sch Med, Dept Mol & Comparat Pathobiol, Johns Hopkins Drug Discovery Program, Baltimore, MD 21205 USA. [Figuera-Losada, Mariana; Slusher, Barbara S.] Johns Hopkins Sch Med, Dept Neurol, Johns Hopkins Drug Discovery Program, Baltimore, MD 21205 USA. [Barnaeva, Elena; Ferrer, Marc] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. [Stathis, Marigo; Thomas, Ajit G.] Johns Hopkins Sch Med, Johns Hopkins Drug Discovery Program, Baltimore, MD 21205 USA. [Dorskind, Joelle M.; Bandaru, Veera V.; Yoo, Seung-Wan; McArthur, Justin C.; Haughey, Norman J.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Haughey, Norman J.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Haughey, Norman J.] Johns Hopkins Sch Med, Dept Behav Sci, Baltimore, MD 21205 USA. [Slusher, Barbara S.] Johns Hopkins Sch Med, Johns Hopkins Drug Discovery Program, Dept Psychiat, Baltimore, MD 21205 USA. [Slusher, Barbara S.] Johns Hopkins Sch Med, Johns Hopkins Drug Discovery Program, Dept Neurosci, Baltimore, MD 21205 USA. EM crojas2@jhmi.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2015 VL 21 SU 1 MA P133 BP S62 EP S62 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DA5ET UT WOS:000367826400134 ER PT J AU Abreu-Vieira, G Xiao, CY Gavrilova, O Reitman, ML AF Abreu-Vieira, Gustavo Xiao, Cuiying Gavrilova, Oksana Reitman, Marc L. TI Integration of body temperature into the analysis of energy expenditure in the mouse SO MOLECULAR METABOLISM LA English DT Article DE Thermoneutrality; Basal metabolic rate; Cold-induced thermogenesis; Body temperature; Energy expenditure; Heat conductance ID BROWN ADIPOSE-TISSUE; BOMBESIN RECEPTOR SUBTYPE-3; METABOLIC-RATE; NONSHIVERING THERMOGENESIS; ENVIRONMENTAL-TEMPERATURE; AMBIENT-TEMPERATURE; MICE; OBESITY; THERMOREGULATION; COLD AB Objectives: We quantified the effect of environmental temperature on mouse energy homeostasis and body temperature. Methods: The effect of environmental temperature (4-33 degrees C) on body temperature, energy expenditure, physical activity, and food intake in various mice (chow diet, high-fat diet, Brs3(-/y), lipodystrophic) was measured using continuous monitoring. Results: Body temperature depended most on circadian phase and physical activity, but also on environmental temperature. The amounts of energy expenditure due to basal metabolic rate (calculated via a novel method), thermic effect of food, physical activity, and cold-induced thermogenesis were determined as a function of environmental temperature. The measured resting defended body temperature matched that calculated from the energy expenditure using Fourier's law of heat conduction. Mice defended a higher body temperature during physical activity. The cost of the warmer body temperature during the active phase is 4-16% of total daily energy expenditure. Parameters measured in diet-induced obese and Brs3-/y mice were similar to controls. The high post-mortem heat conductance demonstrates that most insulation in mice is via physiological mechanisms. Conclusions: At 22 degrees C, cold-induced thermogenesis is similar to 120% of basal metabolic rate. The higher body temperature during physical activity is due to a higher set point, not simply increased heat generation during exercise. Most insulation in mice is via physiological mechanisms, with little from fur or fat. Our analysis suggests that the definition of the upper limit of the thermoneutral zone should be re-considered. Measuring body temperature informs interpretation of energy expenditure data and improves the predictiveness and utility of the mouse to model human energy homeostasis. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Abreu-Vieira, Gustavo; Xiao, Cuiying; Reitman, Marc L.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20982 USA. [Abreu-Vieira, Gustavo] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden. [Gavrilova, Oksana] NIDDK, Mouse Metab Core, NIH, Bethesda, MD 20982 USA. RP Reitman, ML (reprint author), NIDDK, NIH, Bldg 10 CRC,Room 5-5940,10 Ctr Dr, Bethesda, MD 20982 USA. EM gustavo.vieira@su.se; cuiyingx@niddk.nih.gov; OksanaG@BDG10.NIDDK.nih.gov; marc.reitman@nih.gov RI Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; Abreu-Vieira, Gustavo/0000-0003-2861-4023 NR 71 TC 15 Z9 15 U1 7 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2212-8778 J9 MOL METAB JI Mol. Metab. PD JUN PY 2015 VL 4 IS 6 BP 461 EP 470 DI 10.1016/j.molmet.2015.03.001 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CZ9TJ UT WOS:000367439600002 PM 26042200 ER PT J AU Ramos, VFML Pillai, AS Lungu, C Ostrem, J Starr, P Hallett, M AF Ramos, Vesper Fe Marie L. Pillai, Ajay S. Lungu, Codrin Ostrem, Jill Starr, Philip Hallett, Mark TI Intraoperative neurophysiology in deep brain surgery for psychogenic dystonia SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article ID PALLIDAL NEURONAL-ACTIVITY; PARKINSONS-DISEASE; STIMULATION AB Psychogenic dystonia is a challenging entity to diagnose and treat because little is known about its pathophysiology. We describe two cases of psychogenic dystonia who underwent deep brain stimulation when thought to have organic dystonia. The intraoperative microelectrode recordings in globus pallidus internus were retrospectively compared with those of five patients with known DYT1 dystonia using spontaneous discharge parameters of rate and bursting, as well as movement-related discharges. Our data suggest that simple intraoperative neurophysiology measures in single subjects do not differentiate psychogenic dystonia from DYT1 dystonia. C1 [Ramos, Vesper Fe Marie L.; Pillai, Ajay S.; Hallett, Mark] NINDS, Human Motor Control, NIH, Bethesda, MD 20814 USA. [Lungu, Codrin] NINDS, Parkinson Clin, NIH, Bethesda, MD 20814 USA. [Ostrem, Jill] UCSF, Surg Movement Disorders Ctr, San Francisco, CA 94115 USA. [Starr, Philip] Univ Calif San Francisco, Neurol Surg, San Francisco, CA 94143 USA. RP Ramos, VFML (reprint author), NIH, Human Motor Control Sect, Bldg 10,Room 7D42,10 Ctr Dr, Bethesda, MD 20814 USA. EM vesper.ramos@yahoo.com NR 10 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD JUN PY 2015 VL 2 IS 6 BP 707 EP 710 DI 10.1002/acn3.206 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CZ3CV UT WOS:000366982700010 PM 26125045 ER PT J AU Goedert, JJ Gong, YM Hua, X Zhong, HZ He, YM Peng, P Yu, GQ Wang, WJ Ravel, J Shi, JX Zheng, Y AF Goedert, James J. Gong, Yangming Hua, Xing Zhong, Huanzi He, Yimin Peng, Peng Yu, Guoqin Wang, Wenjing Ravel, Jacques Shi, Jianxin Zheng, Ying TI Fecal Microbiota Characteristics of Patients with Colorectal Adenoma Detected by Screening: A Population-based Study SO EBIOMEDICINE LA English DT Article DE Feces; Microbiota; Colorectal cancer; Colorectal adenoma; Cancer screening; China ID HUMAN GUT MICROBIOME; CANCER DEATHS; BACTERIAL; RISK; ASSOCIATION; POLYPECTOMY; BIOMARKERS; DISEASE AB Background: Screening for colorectal cancer (CRC) and precancerous colorectal adenoma (CRA) can detect curable disease. However, participation in colonoscopy and sensitivity of fecal heme for CRA are low. Methods: Microbiota metrics were determined by Illumina sequencing of 16S rRNA genes amplified from DNA extracted from feces self-collected in RNAlater. Among fecal immunochemical test-positive (FIT+) participants, colonoscopically-defined normal versus CRA patients were compared by regression, permutation, and random forest plus leave-one-out methods. Findings: Of 95 FIT+ participants, 61 had successful fecal microbiota profiling and colonoscopy, identifying 24 completely normal patients, 20 CRA patients, 2 CRC patients, and 15 with other conditions. Phylum-level fecal community composition differed significantly between CRA and normal patients (permutation P = 0.02). Rank phylum-level abundance distinguished CRA from normal patients (area under the curve = 0.767, permutation P = 0.006). CRA prevalence was 59% in phylum-level cluster B versus 20% in cluster A (exact P = 0.01). Most of the difference reflected 3-fold higher median relative abundance of Proteobacteria taxa (Wilcoxon signed-rank P = 0.03, positive predictive value = 67%). Antibiotic exposure and other potential confounders did not affect the associations. Interpretation: If confirmed in larger, more diverse populations, fecal microbiota analysis might be employed to improve screening for CRA and ultimately to reduce mortality from CRC. Published by Elsevier B.V. C1 [Goedert, James J.; Hua, Xing; Yu, Guoqin; Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Gong, Yangming; Peng, Peng; Wang, Wenjing; Zheng, Ying] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China. [Zhong, Huanzi; He, Yimin] BGI, Shenzhen, Peoples R China. [Ravel, Jacques] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. RP Goedert, JJ (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E106,MSC 9767, Bethesda, MD 20852 USA. EM goedertj@mail.nih.gov OI Ravel, Jacques/0000-0002-0851-2233 FU Intramural NIH HHS; NCI NIH HHS [Z01CP010214] NR 37 TC 5 Z9 5 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD JUN PY 2015 VL 2 IS 6 BP 597 EP 603 DI 10.1016/j.ebiom.2015.04.010 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CX8KT UT WOS:000365953000023 PM 26288821 ER PT J AU Arama, C Skinner, J Doumtabe, D Portugal, S Tran, TM Jain, A Traore, B Doumbo, OK Davies, DH Troye-Blomberg, M Dolo, A Felgner, PL Crompton, PD AF Arama, Charles Skinner, Jeff Doumtabe, Didier Portugal, Silvia Tran, Tuan M. Jain, Aarti Traore, Boubacar Doumbo, Ogobara K. Davies, David Huw Troye-Blomberg, Marita Dolo, Amagana Felgner, Philip L. Crompton, Peter D. TI Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE antibodies; Dogon; Fulani; malaria; Plasmodium falciparum ID PROTECTIVE IMMUNE-RESPONSE; SYMPATRIC ETHNIC-GROUPS; INFECTED ERYTHROCYTES; INTERETHNIC DIFFERENCES; MEROZOITE ANTIGENS; ANTIBODY-RESPONSES; CLINICAL MALARIA; BURKINA-FASO; WEST-AFRICA; SUSCEPTIBILITY AB Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to < 0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig) M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection. C1 [Arama, Charles; Doumtabe, Didier; Traore, Boubacar; Doumbo, Ogobara K.; Dolo, Amagana] Univ Sci Tech & Technol Bamako, Int Ctr Excellence Res, Dept Epidemiol Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali. [Skinner, Jeff; Portugal, Silvia; Tran, Tuan M.; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Jain, Aarti; Davies, David Huw; Felgner, Philip L.] Univ Calif Irvine, Irvine, CA 92717 USA. [Troye-Blomberg, Marita] Stockholm Univ, Wenner Gren Inst, Dept Immunol, Stockholm, Sweden. RP Crompton, PD (reprint author), NIAID, Immunogenet Lab, NIH, Winbrook 2,Rm 12512441 Parklawn Dr, Rockville, MD 20852 USA. EM pcrompton@niaid.nih.gov RI Troye-Blomberg, Marita/B-9210-2016 OI Troye-Blomberg, Marita/0000-0002-2804-0325 NR 40 TC 3 Z9 3 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 2328-8957 J9 OPEN FORUM INFECT DI JI Open Forum Infect. Dis. PD SUM PY 2015 VL 2 IS 3 DI 10.1093/ofid/ofv118 PG 9 WC Infectious Diseases SC Infectious Diseases GA CX6BP UT WOS:000365786500001 ER PT J AU Fuchs, JD Frank, I Elizaga, ML Allen, M Frahm, N Kochar, N Li, S Edupuganti, S Kalams, SA Tomaras, GD Sheets, R Pensiero, M Tremblay, MA Higgins, TJ Latham, T Egan, MA Clarke, DK Eldridge, JH AF Fuchs, Jonathan D. Frank, Ian Elizaga, Marnie L. Allen, Mary Frahm, Nicole Kochar, Nidhi Li, Sue Edupuganti, Srilatha Kalams, Spyros A. Tomaras, Georgia D. Sheets, Rebecca Pensiero, Michael Tremblay, Marc A. Higgins, Terry J. Latham, Theresa Egan, Michael A. Clarke, David K. Eldridge, John H. CA HVTN 090 Study Grp Natl Inst Allergy Infect Dis HIV TI First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090) SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE dose-escalation; HIV vaccine; immunogenicity; safety; vesicular stomatitis virus ID T-CELL RESPONSES; GENE TRANSLOCATIONS; NONHUMAN-PRIMATES; HIV-1 VACCINE; TYPE-1; VECTORS; NEUROVIRULENCE; ATTENUATION; ANTIBODIES; INFECTION AB Background. We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication- competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods. Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1 gag vaccine at 5 dose levels (4.6 x 10(3) to 3.4 x 10(7) particle forming units) (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral injections at 0 and 2 months. Safety monitoring included VSV cultures from blood, urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were assessed. Results. Local and systemic reactogenicity symptoms were mild to moderate and increased with dose. No severe reactogenicity or product-related serious adverse events were reported, and all rVSV cultures were negative. All vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific T-cell responses were detected in 63% of participants by interferon-gamma enzyme-linked immunospot at the highest dose post boost. Conclusions. An attenuated replication-competent rVSV gag vaccine has an acceptable safety profile in healthy adults. This rVSV vector is a promising new vaccine platform for the development of vaccines to combat HIV-1 and other serious human diseases. C1 [Fuchs, Jonathan D.] San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. [Fuchs, Jonathan D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Frank, Ian] Univ Penn, Philadelphia, PA 19104 USA. [Elizaga, Marnie L.; Frahm, Nicole] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Kochar, Nidhi; Li, Sue] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [Allen, Mary; Sheets, Rebecca; Pensiero, Michael] NIAID, Div Aids, Bethesda, MD 20892 USA. [Edupuganti, Srilatha] Emory Univ, Atlanta, GA 30322 USA. [Kalams, Spyros A.] Vanderbilt Univ, Nashville, TN 37235 USA. [Tomaras, Georgia D.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Tremblay, Marc A.; Higgins, Terry J.; Latham, Theresa; Egan, Michael A.; Clarke, David K.; Eldridge, John H.] Profectus Biosci Inc, Tarrytown, NY USA. RP Fuchs, JD (reprint author), San Francisco Dept Publ Hlth, 25 Van Ness Ave,Suite 500, San Francisco, CA 94102 USA. EM jonathan.fuchs@sfdph.org RI Tomaras, Georgia/J-5041-2016 NR 32 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 2328-8957 J9 OPEN FORUM INFECT DI JI Open Forum Infect. Dis. PD SUM PY 2015 VL 2 IS 3 DI 10.1093/ofid/ofv082 PG 9 WC Infectious Diseases SC Infectious Diseases GA CX6BP UT WOS:000365786500012 ER PT J AU Hahn, KJ Kohli, A Sims, Z Kottilil, S AF Hahn, Katherine J. Kohli, Anita Sims, Zayani Kottilil, Shyamasundaran TI Durable Sustained Virologic Response After Oral Directly Acting Antiviral Therapy Despite Immunosuppressive Treatment SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE DAA; HCV; immunosuppression; SVR ID HEPATITIS-C VIRUS; INFECTION; RELAPSE AB Treatment for hepatitis C has evolved from interferon-based therapy to all oral, directly acting antiviral (DAA) therapy. The influence of immunosuppression on maintaining sustained virologic response (SVR) in patients who have been treated with these directly acting agents is unknown. In this study, we report sustained hepatitis C virus (HCV) suppression in 3 patients undergoing various immunosuppressive treatments after achieving SVR with DAA therapy. Three patients, who were enrolled in 1 of 2 single-center National Institutes of Health clinical trials, achieved SVR12. Each patient had undergone between 6 and 24 weeks of DAA therapy with or without ribavirin. Immunosuppression was varied among the 3 patients. Therapy included adalimumab, carboplatin/irinotecan, or capecitabine. In all 3 cases, patients maintained HCV RNA levels below detection after immunosuppression. All patients had undetectable viral load and normalized liver-related enzymes during immunosuppressive therapy. This report suggests that SVR as a result of novel DAA therapy is durable and likely not affected by immunosuppressive therapy. Larger studies are required to confirm these results, but findings are promising for the treatment of large numbers of HCV-infected patients who may require subsequent immunosuppressive or immunomodulating therapies. C1 [Hahn, Katherine J.] Medstar Georgetown Univ Hosp, Dept Internal Med, Columbia, WA USA. [Kohli, Anita; Sims, Zayani] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Kottilil, Shyamasundaran] Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA. RP Hahn, KJ (reprint author), 3800 Resevoir Rd NW,PHC Floor 5, Washington, DC 20007 USA. EM katherine.j.hahn@medstar.net NR 13 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 2328-8957 J9 OPEN FORUM INFECT DI JI Open Forum Infect. Dis. PD SUM PY 2015 VL 2 IS 3 DI 10.1093/ofid/ofv091 PG 5 WC Infectious Diseases SC Infectious Diseases GA CX6BP UT WOS:000365786500014 ER PT J AU Belzer, ME MacDonell, KK Clark, LF Huang, J Olson, J Kahana, SY Naar, S Sarr, M Thornton, S AF Belzer, Marvin E. MacDonell, Karen Kolmodin Clark, Leslie F. Huang, Jennifer Olson, Johanna Kahana, Shoshana Y. Naar, Sylvie Sarr, Moussa Thornton, Sarah CA Adolescent Med Trials Network HIV TI Acceptability and Feasibility of a Cell Phone Support Intervention for Youth Living with HIV with Nonadherence to Antiretroviral Therapy SO AIDS PATIENT CARE AND STDS LA English DT Article ID INFECTED YOUTH; YOUNG-ADULTS; MEDICATION ADHERENCE; ADOLESCENTS; BARRIERS; PROJECT; HAART; TRIAL; CARE AB A pilot randomized clinical trial of youth ages 15-24 nonadherent to antiretroviral therapy (ART) utilizing daily cell phone support was found to have significant improvement in self-reported adherence and HIV RNA. Understanding acceptability and feasibility is critical for future implementation in clinic settings. Exit interviews were obtained from participants and adherence facilitators (AF). Acceptability was assessed from content analysis of exit interviews. Feasibility was assessed via intervention retention and study retention rates. Thirty-seven eligible youth were enrolled with 19 assigned to the intervention. Seven (37%) discontinued the intervention either due to missing over 20% of calls for two consecutive months (N=5) or missing 10 consecutive calls (N=2). Sixteen participants completed exit interviews, 15 reported the call length was just right, 13 reported they would have liked to continue calls after the 24-week intervention, and all participants reported they would recommend the intervention to friends. Scheduling and making calls required less than 1h per week per participant. Providing cell phone support to youth nonadherent to ART was acceptable and feasible. While the cost is low compared to the price of ART, healthcare systems will need to explore how to cover the cost of providing cell phones (incentive). C1 [Belzer, Marvin E.; Clark, Leslie F.; Olson, Johanna] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA. [Belzer, Marvin E.; Clark, Leslie F.; Olson, Johanna] Univ So Calif, Los Angeles, CA USA. [MacDonell, Karen Kolmodin; Naar, Sylvie] Wayne State Univ, Pediat Prevent Ctr, Detroit, MI USA. [Huang, Jennifer; Sarr, Moussa; Thornton, Sarah] WESTAT Corp, Rockville, MD 20850 USA. [Kahana, Shoshana Y.] NIDA, Bethesda, MD 20892 USA. RP Belzer, ME (reprint author), Childrens Hosp Los Angeles, Dept Pediat, 4650 Sunset Blvd MS 2, Los Angeles, CA 90027 USA. EM mbelzer@chla.usc.edu RI Emchi, Karma/Q-1952-2016 FU NICHD NIH HHS [U01 HD040533, U01-HD040533] NR 24 TC 6 Z9 6 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JUN 1 PY 2015 VL 29 IS 6 BP 338 EP 345 DI 10.1089/apc.2014.0282 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CW1LH UT WOS:000364751200005 PM 25928772 ER PT J AU Resnik, DB AF Resnik, David B. TI How to think seriously about the planet: the case for environmental conservatism SO Monash Bioethics Review LA English DT Book Review C1 [Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1321-2753 EI 1836-6716 J9 MONASH BIOETH REV JI Monash Bioeth. Rev. PD JUN PY 2015 VL 33 IS 2-3 BP 229 EP 230 DI 10.1007/s40592-014-0013-8 PG 2 WC Ethics SC Social Sciences - Other Topics GA CV6ZU UT WOS:000364422000013 PM 26530996 ER PT J AU Vajda, S You, D Antani, S Thoma, G AF Vajda, Szilard You, Daekeun Antani, Sameer Thoma, George TI Large image modality labeling initiative using semi-supervised and optimized clustering SO INTERNATIONAL JOURNAL OF MULTIMEDIA INFORMATION RETRIEVAL LA English DT Article DE Semi-automatic image annotation; Medical image modality detection; Unsupervised clustering AB Medical image modality detection is a key step for indexing images from biomedical articles. Traditionally, complex supervised classification methods have been used for this. However, they rely on proportionally sized labeled training samples. With the increase in availability of image data it has become increasingly challenging to obtain reasonably accurate manual labels to train classifiers. Toward meeting this shortcoming, we propose a semi-automatic labeling strategy that reduces the human annotator effort. Each image is projected into several feature spaces, and each entry in these spaces is clustered in an unsupervised manner. The cluster centers for each feature representation are then labeled by a human annotator, and the labels propagated through each cluster. To find the optimal cluster numbers for each feature space, a so-called "jump" method is used. The final label of an image is decided by a voting scheme that summarizes the different opinions on the same image provided by the different feature representations. The proposed method is evaluated on ImageCLEFmed2012 data set containing approximately 300,000 images, and showed that annotating <1% of the data is sufficient to label correctly 49.95% of the images. The method spared approximately 700 h of human annotation labor and associated costs. C1 [Vajda, Szilard; You, Daekeun; Antani, Sameer; Thoma, George] Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Vajda, S (reprint author), Natl Lib Med, NIH, Bethesda, MD 20894 USA. EM szilard.vajda@nih.gov NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2192-6611 EI 2192-662X J9 INT J MULTIMED INF R JI Int. J. Multimed. Inf. Retr. PD JUN PY 2015 VL 4 IS 2 SI SI BP 143 EP 151 DI 10.1007/s13735-015-0078-z PG 9 WC Computer Science, Software Engineering SC Computer Science GA CU9VW UT WOS:000363895500006 ER PT J AU Wells, SA Asa, SL Dralle, H Elisei, R Evans, DB Gagel, RF Lee, N Machens, A Moley, JF Pacini, F Raue, F Frank-Raue, K Robinson, B Rosenthal, MS Santoro, M Schlumberger, M Shah, M Waguespack, SG AF Wells, Samuel A., Jr. Asa, Sylvia L. Dralle, Henning Elisei, Rossella Evans, Douglas B. Gagel, Robert F. Lee, Nancy Machens, Andreas Moley, Jeffrey F. Pacini, Furio Raue, Friedhelm Frank-Raue, Karin Robinson, Bruce Rosenthal, M. Sara Santoro, Massimo Schlumberger, Martin Shah, Manisha Waguespack, Steven G. TI Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma SO THYROID LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; RET PROTOONCOGENE MUTATIONS; PREIMPLANTATION GENETIC DIAGNOSIS; GENOTYPE-PHENOTYPE CORRELATION; CUTANEOUS LICHEN AMYLOIDOSIS; ELEVATED CALCITONIN LEVELS; C-CELL HYPERPLASIA; OF-THE-LITERATURE; FINE-NEEDLE-ASPIRATION; LYMPH-NODE METASTASES AB Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice. C1 [Wells, Samuel A., Jr.] NCI, NIH, Genet Branch, Bethesda, MD 20814 USA. [Asa, Sylvia L.] Univ Toronto, Dept Pathol, Univ Hlth Network, Toronto, ON, Canada. [Asa, Sylvia L.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Dralle, Henning; Machens, Andreas] Univ Halle Wittenberg, Univ Hosp, Dept Gen Visceral & Vasc Surg, D-06108 Halle, Germany. [Elisei, Rossella] Univ Pisa, Dept Endocrinol, Pisa, Italy. [Evans, Douglas B.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Gagel, Robert F.; Waguespack, Steven G.] Univ Texas MD Anderson Canc Ctr, Div Internal Med, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. [Lee, Nancy] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Moley, Jeffrey F.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Pacini, Furio] Univ Siena, Policlin Santa Maria Scotte, Dept Internal Med Endocrinol & Metab & Biochem, Sect Endocrinol & Metab, I-53100 Siena, Italy. [Raue, Friedhelm; Frank-Raue, Karin] Heidelberg Univ, Fac Med, Moleculargenet Lab, Endocrine Practice, Heidelberg, Germany. [Robinson, Bruce] Univ Sydney, Sch Med, Sydney, NSW 2006, Australia. [Rosenthal, M. Sara] Univ Kentucky, Dept Internal Med, Lexington, KY USA. [Rosenthal, M. Sara] Univ Kentucky, Dept Pediat, Lexington, KY USA. [Rosenthal, M. Sara] Univ Kentucky, Dept Behav Sci, Lexington, KY USA. [Santoro, Massimo] Univ Naples Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy. [Schlumberger, Martin] Univ Paris 11, Inst Gustave Roussy, Serv Med Nucl, Villejuif, France. [Shah, Manisha] Ohio State Univ, Dept Internal Med, Div Med Oncol, Columbus, OH 43210 USA. RP Wells, SA (reprint author), NCI, NIH, Canc Genet Branch, Bldg 37,Room 6138,37 Convent Dr, Bethesda, MD 20814 USA. EM wellss@mail.nih.gov FU Thyroid Cancer Survivors' Association, Inc., (ThyCa); American Thyroid Association FX The ATA Guidelines Task Force would like to thank and acknowledge those who were of great help during the development of the revised guidelines: Ms. Bobbi Smith, Executive Director of the ATA, and the staff at the ATA, for their continuing involvement and support during the preparation of the manuscript; Ms. Alicia A. Livinski, Biomedical Librarian, National Institutes of Health Library for assistance with the manuscript and bibliography; Dr. Susan Shaw De-Vesa, Biostatistics Branch, National Cancer Institute, for help in calculating the incidence of MEN2A and of MEN2B using the Surveillance, Epidemiology, and End Results (SEER) Stat version 8.1.2 Rate Session. Access the SEER 18 database at www.seer.cancer.gov). Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2012 Sub (2000-2010) < Katrina/Rita Population Adjustment >- Linked To County Attributes - Total U.S., 1969-2011 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2013, based on the November 2012 submission. The Thyroid Cancer Survivors' Association, Inc., (ThyCa) for contributing an unrestricted educational grant towards the development of the Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma. The American Thyroid Association provided the remainder of the funding. There was no commercial support. NR 372 TC 133 Z9 138 U1 7 U2 16 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JUN 1 PY 2015 VL 25 IS 6 BP 567 EP 610 DI 10.1089/thy.2014.0335 PG 44 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU9WN UT WOS:000363897500001 PM 25810047 ER PT J AU Sittampalam, S Eglen, R Ferguson, S Maynes, JT Olden, K Schrader, L Shelper, T Ferrer, M AF Sittampalam, Sitta Eglen, Richard Ferguson, Stephen Maynes, Jason Thomas Olden, Kenneth Schrader, Laura Shelper, Todd Ferrer, Marc TI Three-Dimensional Cell Culture Assays: Are They More Predictive of In Vivo Efficacy than 2D Monolayer Cell-Based Assays? SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES LA English DT Editorial Material C1 [Sittampalam, Sitta] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Eglen, Richard] Corning Life Sci, Tewksbury, MA USA. [Ferguson, Stephen] Natl Inst Environm Sci, Mol Toxicol & Informat Grp, Biomol Screening, NIH, Res Triangle Pk, NC USA. [Maynes, Jason Thomas] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Olden, Kenneth] US EPA, Natl Ctr Environm Assessment, Arlington, VA USA. [Schrader, Laura] 3D Biomatrix, Ann Arbor, MI USA. [Shelper, Todd] Griffith Univ, Avery Grp, Eskitis Inst Drug Discovery, Nathan, Qld 4111, Australia. [Ferrer, Marc] NIH, Biomol Screening & Probe Dev, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. RP Sittampalam, S (reprint author), NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-658X EI 1557-8127 J9 ASSAY DRUG DEV TECHN JI ASSAY DRUG DEV. TECHNOL. PD JUN 1 PY 2015 VL 13 IS 5 BP 254 EP 261 DI 10.1089/adt.2015.29001.rtd PG 8 WC Biochemical Research Methods; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA CU9YE UT WOS:000363902200003 PM 26120951 ER PT J AU Thorpe, RJ Duru, OK Hill, CV AF Thorpe, Roland J., Jr. Duru, O. Kenrik Hill, Carl V. TI ADVANCING RACIAL/ETHNIC MINORITY MEN'S HEALTH USING A LIFE COURSE APPROACH SO ETHNICITY & DISEASE LA English DT Editorial Material DE Minority Men's Health; Life Course; Health Disparities ID AFRICAN-AMERICAN MEN; EPIDEMIOLOGY; FRAMEWORK C1 [Thorpe, Roland J., Jr.] Johns Hopkins Bloomberg Sch Publ Hlth, Hopkins Ctr Hlth Dispar Solut, Program Res Mens Hlth, Baltimore, MD 21205 USA. [Thorpe, Roland J., Jr.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA. [Duru, O. Kenrik] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. [Hill, Carl V.] NIA, Off Special Populat, NIH, Bethesda, MD 20892 USA. RP Thorpe, RJ (reprint author), 624 N Broadway,Ste 708, Baltimore, MD 21205 USA. EM rthorpe@jhu.edu FU NIA NIH HHS [R01AG040100, P30 AG021684, R01 AG040100, P30 AG015281, P30-AG15281]; NIMHD NIH HHS [P30MD000214, L60 MD001407, P60 MD000214] NR 17 TC 3 Z9 3 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2015 VL 25 IS 3 BP 241 EP 244 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU7KW UT WOS:000363717800002 PM 26674116 ER PT J AU Hill, CV Perez-Stable, EJ Anderson, NA Bernard, MA AF Hill, Carl V. Perez-Stable, Eliseo J. Anderson, Norman A. Bernard, Marie A. TI THE NATIONAL INSTITUTE ON AGING HEALTH DISPARITIES RESEARCH FRAMEWORK SO ETHNICITY & DISEASE LA English DT Article DE Aging; Health Disparities ID NUTRITION EXAMINATION SURVEY; RESIDENTIAL SEGREGATION; SOCIOECONOMIC-STATUS; LIFE-COURSE; CARDIOVASCULAR-DISEASE; RACIAL DISPARITIES; ETHNIC DISPARITIES; TELOMERE LENGTH; RISK-FACTORS; CARE AB Objective: Development of a new framework for the National Institute on Aging (NIA) to assess progress and opportunities toward stimulating and supporting rigorous research to address health disparities. Design: Portfolio review of NIA's health disparities research portfolio to evaluate NIA's progress in addressing priority health disparities areas. Results: The NIA Health Disparities Research Framework highlights important factors for health disparities research related to aging, provides an organizing structure for tracking progress, stimulates opportunities to better delineate causal pathways and broadens the scope for malleable targets for intervention, aiding in our efforts to address health disparities in the aging population. Conclusions: The promise of health disparities research depends largely on scientific rigor that builds on past findings and aggressively pursues new approaches. The NIA Health Disparities Framework provides a landscape for stimulating interdisciplinary approaches, evaluating research productivity and identifying opportunities for innovative health disparities research related to aging. C1 [Hill, Carl V.; Bernard, Marie A.] NIA, NIH, Bethesda, MD 20814 USA. [Perez-Stable, Eliseo J.] Univ Calif San Francisco, Dept Med, Ctr Aging Diverse Communities, San Francisco, CA USA. [Anderson, Norman A.] Amer Psychol Assoc, Washington, DC USA. RP Hill, CV (reprint author), NIA, Off Special Populat, NIH, Bldg 31,31 Ctr Dr, Bethesda, MD 20814 USA. EM hillcv@mail.nih.gov FU Center for Aging in Diverse Communities [P30 AG15272] FX Eliseo J. Perez-Stable, MD is professor of Medicine and chief of the Division of General Internal Medicine, Department of Medicine at the University of California, San Francisco School of Medicine (UCSF). He is the director of the UCSF Medical Effectiveness Research Center for Diverse Populations (MERC) and of the Center for Aging in Diverse Communities, which is funded grant (P30 AG15272) and active through 2017. Dr. Perez-Stable is a retired member of NIA's National Advisory Council on Aging, and past chairperson for its Task Force on Minority Aging and Health Disparities Research. In May 2015, Dr. Perez-Stable was named director of the NIH's National Institute on Minority Health and Health Disparities (NIMHD) where he will oversee the institute's activities to improve minority health and reduce health disparities. NR 59 TC 0 Z9 0 U1 3 U2 3 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2015 VL 25 IS 3 BP 245 EP 254 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU7KW UT WOS:000363717800003 PM 26675362 ER PT J AU Commodore-Mensah, Y Himmelfarb, CD Agyemang, C Sumner, AE AF Commodore-Mensah, Yvonne Himmelfarb, Cheryl Dennison Agyemang, Charles Sumner, Anne E. TI CARDIOMETABOLIC HEALTH IN AFRICAN IMMIGRANTS TO THE UNITED STATES: A CALL TO RE-EXAMINE RESEARCH ON AFRICAN-DESCENT POPULATIONS SO ETHNICITY & DISEASE LA English DT Editorial Material DE African Immigrants; African Diaspora; Health Disparities; Cardiometabolic Health; Cardiovascular Disease; Migration ID NEW-YORK-CITY; ORIGIN POPULATIONS; BLACK-AFRICAN; HEART-DISEASE; AMERICAN MEN; WEST-AFRICA; HYPERTENSION; PREVALENCE; ETHNICITY; GHANAIAN AB In the 20th century, Africans in Sub-Saharan Africa had lower rates of cardiometabolic disease than Africans who migrated. However, in the 21st century, beyond infectious diseases, the triple epidemics of obesity, diabetes and hypertension have taken hold in Africa. Therefore, Africans are acquiring these chronic diseases at different rates and different intensity prior to migration. To ensure optimal care and health outcomes, the United States practice of grouping all African-descent populations into the "Black/African American" category without regard to country of origin masks socioeconomic and cultural differences and needs re-evaluation. Overall, research on African-descent populations would benefit from a shift from a racial to an ethnic perspective. To demonstrate the value of disaggregating data on African-descent populations, the epidemiologic transition, social, economic, and health characteristics of African immigrants are presented. C1 [Commodore-Mensah, Yvonne] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Agyemang, Charles] Univ Amsterdam, Acad Med Ctr, Dept Publ Hlth, NL-1105 AZ Amsterdam, Netherlands. [Sumner, Anne E.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Commodore-Mensah, Y (reprint author), 525 North Wolfe St,Room 332, Baltimore, MD 21205 USA. EM ycommod1@jhu.edu NR 50 TC 4 Z9 4 U1 3 U2 3 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2015 VL 25 IS 3 BP 373 EP 380 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU7KW UT WOS:000363717800018 PM 26675140 ER PT J AU Chio, A Barberis, M Brunetti, M Restagno, G Sabatelli, M Zollino, M Giannini, F Conforti, F Caponnetto, C Mandich, P Mandrioli, J Penco, S Lunetta, C Borghero, G Murru, MR Monsurro, MR Volanti, P Simone, I Logroscino, G Logullo, F Salvi, F Riva, N Traynor, B Mora, G Calvo, A AF Chio, A. Barberis, M. Brunetti, M. Restagno, G. Sabatelli, M. Zollino, M. Giannini, F. Conforti, F. Caponnetto, C. Mandich, P. Mandrioli, J. Penco, S. Lunetta, C. Borghero, G. Murru, M. R. Monsurro, M. R. Volanti, P. Simone, I. Logroscino, G. Logullo, F. Salvi, F. Riva, N. Traynor, B. Mora, G. Calvo, A. TI HFE p.His63Asp polymorphism is not a modifier of ALS phenotype SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 1st Congress of the European-Academy-of-Neurology CY JUN, 2015 CL Berlin, GERMANY SP European Acad Neurol C1 [Chio, A.; Barberis, M.; Brunetti, M.; Calvo, A.] Univ Turin, I-10124 Turin, Italy. [Restagno, G.] AOU Citta Salute & Sci, Turin, Italy. [Sabatelli, M.; Zollino, M.] Univ Cattolica Roma, Rome, Italy. [Giannini, F.] Univ Siena, I-53100 Siena, Italy. [Conforti, F.] CNR Mangone, Mangone, Italy. [Caponnetto, C.; Mandich, P.] Univ Genoa, Genoa, Italy. [Mandrioli, J.] Univ Modena, I-41100 Modena, Italy. [Penco, S.] Osped Niguarda Ca Granda, Milan, Italy. [Lunetta, C.] Ctr Clin NEMO, Milan, Italy. [Borghero, G.; Murru, M. R.] Univ Cagliari, Cagliari, Italy. [Monsurro, M. R.] Univ Naples Federico II, Naples, Italy. [Volanti, P.] Fond Maugeri Mistretta, Mistretta, Italy. [Simone, I.; Logroscino, G.] Univ Bari, I-70121 Bari, Italy. [Logullo, F.] Univ Ancona, Ancona, Italy. [Salvi, F.] Univ Bologna, Bologna, Italy. [Riva, N.] Hosp San Raffaele, I-20132 Milan, Italy. [Traynor, B.] NIA, NIH, Bethesda, MD 20892 USA. [Mora, G.] Fdn Maugeri Milano, Milan, Italy. RI LOGROSCINO, GIANCARLO/K-5148-2016; riva, nilo/J-7187-2012 OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; riva, nilo/0000-0002-0513-9517 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 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUN PY 2015 VL 22 SU 1 SI SI MA O2212 BP 81 EP 81 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CL5WN UT WOS:000357033500127 ER PT J AU Tasca, G Monforte, M Brisca, G D'Amico, A Diaz-Manera, J Maggi, L Al Shaik, N Pichiecchio, A Berardinelli, A Lokken, N Munell, F Sanchez, A Morandi, L Voermans, N Dastgir, J Walter, MC Bonnemann, C Straub, V Quijano-Roy, S Carlier, R Vissing, J Mercuri, E Muntoni, F Ricci, E Bertini, E Udd, B Bruno, C AF Tasca, G. Monforte, M. Brisca, G. D'Amico, A. Diaz-Manera, J. Maggi, L. Al Shaik, N. Pichiecchio, A. Berardinelli, A. Lokken, N. Munell, F. Sanchez, A. Morandi, L. Voermans, N. Dastgir, J. Walter, M. C. Boennemann, C. Straub, V. Quijano-Roy, S. Carlier, R. Vissing, J. Mercuri, E. Muntoni, F. Ricci, E. Bertini, E. Udd, B. Bruno, C. TI Muscle MRI in sarcoglycanopathies SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 1st Congress of the European-Academy-of-Neurology CY JUN, 2015 CL Berlin, GERMANY SP European Acad Neurol C1 [Brisca, G.; Bruno, C.] IRCCS Giannina Gaslini, Genoa, Italy. [D'Amico, A.] Bambino Gesu Childrens Res Hosp, Rome, Italy. [Maggi, L.; Morandi, L.] Fdn Neurol Inst Carlo Besta, Milan, Italy. [Al Shaik, N.] Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England. [Pichiecchio, A.; Berardinelli, A.] C Mondino Natl Neurol Inst, Pavia, Italy. [Lokken, N.] Univ Copenhaegn, Rigshosp, Copenhagen, Denmark. [Munell, F.; Sanchez, A.] Vall dHebron Univ Hosp, Barcelona, Spain. [Voermans, N.] NIJMEGEN GLD, Nijmegen, Netherlands. [Dastgir, J.] NINDS, NIH, Bethesda, MD 20892 USA. [Quijano-Roy, S.; Carlier, R.] Hop Raymond Poincare, Garches, France. [Mercuri, E.] Univ Cattolica Sacro Cuore, Sch Med, I-00168 Rome, Italy. RI d'amico, adele/J-9203-2016 OI d'amico, adele/0000-0003-2438-2624 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 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUN PY 2015 VL 22 SU 1 SI SI MA P1265 BP 206 EP 206 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CL5WN UT WOS:000357033500336 ER PT J AU Chio, A Calvo, A Barberis, M Brunetti, M Restagno, G Mora, G Sabatelli, M Battistini, S Conforti, F Caponnetto, C Mandrioli, J Mandich, P Zollino, M Borghero, G Murru, MR Monsurro, MR Volanti, P Simone, I Logroscino, G Salvi, F Logullo, F Penco, S Lunetta, C Traynor, B AF Chio, A. Calvo, A. Barberis, M. Brunetti, M. Restagno, G. Mora, G. Sabatelli, M. Battistini, S. Conforti, F. Caponnetto, C. Mandrioli, J. Mandich, P. Zollino, M. Borghero, G. Murru, M. R. Monsurro, M. R. Volanti, P. Simone, I. Logroscino, G. Salvi, F. Logullo, F. Penco, S. Lunetta, C. Traynor, B. TI CHCHD10 gene mutations in Italian sporadic and familial ALS patients SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 1st Congress of the European-Academy-of-Neurology CY JUN, 2015 CL Berlin, GERMANY SP European Acad Neurol C1 [Calvo, A.; Barberis, M.; Brunetti, M.] Univ Turin, Turin, Italy. [Restagno, G.] AOU Citta Salute & Sci, Turin, Italy. [Mora, G.] Fdn Maugeri Milano, Milan, Italy. [Sabatelli, M.; Zollino, M.] Univ Cattolica Roma, Rome, Italy. [Battistini, S.] Univ Siena, Siena, Italy. [Conforti, F.] CNR Mangone, Mangone, Italy. [Caponnetto, C.; Mandich, P.] Univ Genua, Genoa, Italy. [Mandrioli, J.] Univ Modena, I-41100 Modena, Italy. [Borghero, G.; Murru, M. R.] Univ Cagliari, Cagliari, Italy. [Monsurro, M. R.] Univ Naples Federico II, Naples, Italy. [Volanti, P.] Fond Maugeri Mistretta, Mistretta, Italy. [Simone, I.; Logroscino, G.] Univ Bari, Bari, Italy. [Salvi, F.] Univ Bologna, Bologna, Italy. [Logullo, F.] Univ Ancona, Ancona, Italy. [Penco, S.] Osped Niguarda Ca Granda, Milan, Italy. [Lunetta, C.] Ctr Clin NEMO, Milan, Italy. [Traynor, B.] NIA, NIH, Bethesda, MD 20892 USA. RI LOGROSCINO, GIANCARLO/K-5148-2016 OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242 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 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUN PY 2015 VL 22 SU 1 SI SI MA P2171 BP 260 EP 260 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CL5WN UT WOS:000357033500430 ER PT J AU Abu-Asab, MS Ardeljan, C Chan, CC AF Abu-Asab, Mones S. Ardeljan, Christopher Chan, Chi-Chao TI Ocular Ultrastructural Features of Gaucher Disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Abu-Asab, Mones S.; Ardeljan, Christopher; Chan, Chi-Chao] NEI, Immunol Lab, Sect Immunopath, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3412 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891101052 ER PT J AU Arjunan, P Tang, ZS Dong, LJ Wu, ZJ Martin, PM Christopher, CW Li, XR AF Arjunan, Pachiappan Tang, Zhongshu Dong, Lijin Wu, Zhijian Martin, Pamela M. Christopher, Cutler W. Li, Xuri TI Neuro and vasoprotective effects of vascular endothelial growth factor-B in Retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Arjunan, Pachiappan; Martin, Pamela M.] Georgia Regents Univ, Biochem & Mol Biol, Augusta, GA USA. [Tang, Zhongshu; Li, Xuri] Sun Yat Sen Univ, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China. [Dong, Lijin; Wu, Zhijian] NEI, Bethesda, MD 20892 USA. [Christopher, Cutler W.] Georgia Regents Univ, Periodont, Augusta, GA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3646 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891101271 ER PT J AU Biswas, P Chavali, VRM Agnello, G Duncan, JL Naeem, MA Riazuddin, S Hejtmancik, JF Georgiou, G Riazuddin, SA Ayyagari, R AF Biswas, Pooja Chavali, Venkata R. M. Agnello, Giulia Duncan, Jacque L. Naeem, Muhammad Asif Riazuddin, Sheikh Hejtmancik, James Fielding Georgiou, George Riazuddin, S. Amer Ayyagari, Radha TI Identification of a mutation in ASRGL1 as the underlying cause of early-onset recessive Retinal Degeneration (RD) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Biswas, Pooja; Ayyagari, Radha] Univ Calif San Diego, Jacobs Retina Ctr, San Diego, CA 92103 USA. [Chavali, Venkata R. M.] Univ Penn, Ophthalmol, Philadelphia, PA 19104 USA. [Agnello, Giulia; Georgiou, George] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. [Duncan, Jacque L.] Univ Calif SF, Ophthalmol, San Francisco, CA USA. [Naeem, Muhammad Asif; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. [Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. [Hejtmancik, James Fielding] NEI, OMGS OGVFB, Bethesda, MD 20892 USA. [Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Johns Hopkins Wilmer Eye Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4348 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891103136 ER PT J AU Campla, CK Kim, JW Yang, HJ Swaroop, A AF Campla, Christie Kay Kim, Jung-Woong Yang, Hyun-Jin Swaroop, Anand TI Identification of FERM and PDZ domain containing 1 (Frmpd1) as a candidate gene necessary for rod photoreceptor maturation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Campla, Christie Kay; Kim, Jung-Woong; Yang, Hyun-Jin; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. [Campla, Christie Kay] Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX2 6AW, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5388 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891105300 ER PT J AU Caspi, RR van Panhuys, N Chen, J Silver, P Jittayasothorn, Y Germain, RN Chong, WP AF Caspi, Rachel R. van Panhuys, Nicholas Chen, Jun Silver, Phyllis Jittayasothorn, Yingyos Germain, Ronald N. Chong, Wai Po TI NK-DC crosstalk controls the autopathogenic suppresses uveitis through an innate IFN-gamma/IL-27 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Caspi, Rachel R.; Chen, Jun; Silver, Phyllis; Jittayasothorn, Yingyos; Chong, Wai Po] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [van Panhuys, Nicholas; Germain, Ronald N.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3207 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891100082 ER PT J AU Cheng, CY Fan, Q Verhoeven, VJM Guggenheim, JA Bailey-Wilson, J Stambolian, D Wong, TY Klaver, CCW Baird, PN Saw, SM AF Cheng, Ching-Yu Fan, Qiao Verhoeven, Virginie J. M. Guggenheim, Jeremy A. Bailey-Wilson, Joan Stambolian, Dwight Wong, Tien Yin Klaver, Caroline C. W. Baird, Paul N. Saw, Seang-Mei CA Consortium Refractive Error Myopia TI Multiple novel loci for corneal curvature identified through genome-wide association studies: The CREAM Consortium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Cheng, Ching-Yu; Fan, Qiao] Singapore Eye Res Inst, Ocular Epidemiol Res Grp, Singapore, Singapore. [Cheng, Ching-Yu; Wong, Tien Yin] Duke NUS Grad Med Sch, Singapore, Singapore. [Verhoeven, Virginie J. M.; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands. [Verhoeven, Virginie J. M.; Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Guggenheim, Jeremy A.] Hong Kong Polytech Univ, Ctr Myopia Res, Hong Kong, Hong Kong, Peoples R China. [Bailey-Wilson, Joan] NHGRI, Computat & Stat Genom Branch, Baltimore, MD USA. [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Wong, Tien Yin] Singapore Natl Eye Ctr, Singapore, Singapore. [Baird, Paul N.] Ctr Eye Res Australia, Ocular Genet Unit, Melbourne, Vic, Australia. [Saw, Seang-Mei] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Saw, Seang-Mei] Natl Univ Hlth Syst, Singapore, Singapore. [Saw, Seang-Mei] Singapore Eye Res Inst, Myopia Res Grp, Singapore, Singapore. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4351 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891103139 ER PT J AU Connaughton, VP Nelson, RF AF Connaughton, Victoria P. Nelson, Ralph F. TI Ultraviolet dominates ganglion cell light responses in larval zebrafish retinas SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Connaughton, Victoria P.] Amer Univ, Biol, Washington, DC 20016 USA. [Nelson, Ralph F.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3251 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891100122 ER PT J AU Cukras, CA Flamendorf, J Ayyagari, R Wong, WT Sieving, PA AF Cukras, Catherine A. Flamendorf, Jason Ayyagari, Radha Wong, Wai T. Sieving, Paul A. TI Longitudinal changes in Late-Onset Retinal Degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Cukras, Catherine A.; Flamendorf, Jason; Wong, Wai T.; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. [Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3842 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891102054 ER PT J AU Dolinska, MB Wingfield, PT Farney, S Brooks, BP Sergeev, YV AF Dolinska, Monika B. Wingfield, Paul T. Farney, Sara Brooks, Brian Patrick Sergeev, Yuri V. TI Oculocutaneous albinism Type 1 mutations indicate changes in the recombinant tyrosinase folding and activity. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Dolinska, Monika B.; Farney, Sara; Brooks, Brian Patrick; Sergeev, Yuri V.] NEI, OGVFB, Bethesda, MD 20892 USA. [Wingfield, Paul T.] NIAMS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4665 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891104029 ER PT J AU Duncan, T Ayele, M Samuel, W Kutty, RK Redmond, TM AF Duncan, Todd Ayele, Michael Samuel, William Kutty, R. Krishnan Redmond, T. Michael TI Secretome Analysis of Human Retinal Pigment Epithelial Cells in Culture SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Duncan, Todd; Ayele, Michael; Samuel, William; Kutty, R. Krishnan; Redmond, T. Michael] NEI, LRCMB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4228 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891103018 ER PT J AU Duvesh, R Krishnadas, SR Puthuran, G Rajendrababu, S Venkatesh, R Kavitha, S Ramulu, PY Wojciechowski, R Sundaresan, P Angle, P AF Duvesh, Roopam Krishnadas, S. R. Puthuran, George Rajendrababu, Sharmila Venkatesh, Rengaraj Kavitha, Srinivasan Ramulu, Pradeep Y. Wojciechowski, Robert Sundaresan, Periasamy Angle, Primary CA Primary Angle Closure Glaucoma TI Cytokines and chemokines profile in aqueous humor of PACG eyes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Duvesh, Roopam; Sundaresan, Periasamy] Aravind Med Res Fdn, Dept Genet, Madurai, Tamil Nadu, India. [Krishnadas, S. R.; Puthuran, George; Rajendrababu, Sharmila; Venkatesh, Rengaraj; Kavitha, Srinivasan] Aravind Eye Hosp, Glaucoma Clin, Madurai, Tamil Nadu, India. [Ramulu, Pradeep Y.] Johns Hopkins Univ Hosp, Glaucoma Div, Baltimore, MD 21287 USA. [Wojciechowski, Robert] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Wojciechowski, Robert] NHGRI, Inherited Dis Res Branch, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3482 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891101121 ER PT J AU Gunther, RC Toth, CA Veerappan, M Michelson, M Tai, V Winter, K Folgar, FA Chew, EY Farsiu, S AF Gunther, Randall C. Toth, Cynthia A. Veerappan, Malini Michelson, Michelle Tai, Vincent Winter, Katrina Folgar, Francisco A. Chew, Emily Y. Farsiu, Sina TI Association of drusen substructure findings on SD-OCT with abnormal drusen volumes and progression to choroidal neovascularization in the AREDS2 Ancillary Study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Gunther, Randall C.; Toth, Cynthia A.; Veerappan, Malini; Michelson, Michelle; Tai, Vincent; Winter, Katrina; Folgar, Francisco A.; Farsiu, Sina] Duke Univ, Med Ctr, Ophthalmol, Durham, NC USA. [Toth, Cynthia A.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. [Chew, Emily Y.] NEI, Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5146 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891105076 ER PT J AU Hasan, J Agron, E Clemons, TE Wong, WT Cukras, CA Chew, EY AF Hasan, Jesia Agron, Elvira Clemons, Traci E. Wong, Wai T. Cukras, Catherine A. Chew, Emily Y. TI Twenty-year follow-up of age related macular degeneration in the Age-Related Eye Disease Study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Hasan, Jesia; Agron, Elvira; Clemons, Traci E.; Wong, Wai T.; Cukras, Catherine A.; Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3792 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891102004 ER PT J AU Hernandez-Pinto, AM Subramanian, P Polato, F de la Rocha, A De la Rosa, EJ Becerra, P AF Hernandez-Pinto, Alberto M. Subramanian, Preeti Polato, Federica de la Rocha, Andres De la Rosa, Enrique J. Becerra, Patricia TI PEDF-derived Peptides delay Photoreceptor Cell Death in two Experimental Models of Retinitis Pigmentosa. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Hernandez-Pinto, Alberto M.; de la Rocha, Andres; De la Rosa, Enrique J.] Ctr Invest Biol, E-28006 Madrid, Spain. [Subramanian, Preeti; Polato, Federica; Becerra, Patricia] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5413 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891105325 ER PT J AU Huryn, L Manoli, I Harrington, E Sloan, J Brooks, BP Venditti, C Zein, WM AF Huryn, Laryssa Manoli, Irini Harrington, Elizabeth Sloan, Jennifer Brooks, Brian Patrick Venditti, Charles Zein, Wadih M. TI Optic Nerve Atrophy in Methylmalonic Acidemia (MMA) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Huryn, Laryssa; Brooks, Brian Patrick; Zein, Wadih M.] NEI, Bethesda, MD 20892 USA. [Manoli, Irini; Harrington, Elizabeth; Sloan, Jennifer; Venditti, Charles] NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5554 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891106052 ER PT J AU Jeffrey, BG Cukras, CA Zein, WM Turriff, A Brooks, BP AF Jeffrey, Brett G. Cukras, Catherine A. Zein, Wadih M. Turriff, Amy Brooks, Brian Patrick TI Retinal Function and Structure Correlations in ABCA4 Retinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Jeffrey, Brett G.; Cukras, Catherine A.; Zein, Wadih M.; Turriff, Amy; Brooks, Brian Patrick] NEI, Ophthalm Genet & Visual Funct, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3821 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891102033 ER PT J AU Jha, BS Lal, M Sharma, R Hua, F Ferrer, M Bharti, K AF Jha, Balendu Shekhar Lal, Madhu Sharma, Ruchi Hua, Fang Ferrer, Marc Bharti, Kapil TI A High-throughput Screen to Identify Candidate Drugs to Prevent Proteotoxic Stress-Induced Retinal Pigment Epithelium Cell Death SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Jha, Balendu Shekhar; Sharma, Ruchi; Hua, Fang; Bharti, Kapil] NEI, NIH, Bethesda, MD 20892 USA. [Lal, Madhu; Ferrer, Marc] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4207 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891102408 ER PT J AU Jun, G Chung, J Igo, RP Bailey-Wilson, J Stambolian, D Cheng, CY Mitchell, P Chew, EY Wang, JJ Iyengar, SK AF Jun, Gyungah Chung, Jaeyoon Igo, Robert P. Bailey-Wilson, Joan Stambolian, Dwight Cheng, Ching-Yu Mitchell, Paul Chew, Emily Y. Wang, Jie Jin Iyengar, Sudha K. TI A Genome-Wide Association Study of Age-Related Cortical Cataract and Its Progression Identifies Novel Genes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Jun, Gyungah; Chung, Jaeyoon] Boston Univ, Med, Boston, MA 02215 USA. [Jun, Gyungah] Boston Univ, Ophthalmol, Boston, MA 02215 USA. [Igo, Robert P.; Iyengar, Sudha K.] Case Western Reserve Univ, Epidemiol & Biostat, Cleveland, OH 44106 USA. [Bailey-Wilson, Joan] NHGRI, Computat & Stat Genom Branch, Baltimore, MD USA. [Stambolian, Dwight] Univ Penn, Ophthalmol, Philadelphia, PA 19104 USA. [Cheng, Ching-Yu] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Cheng, Ching-Yu] Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore. [Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Ophthalmol, Sydney, ACT, Australia. [Chew, Emily Y.] NEI, Bethesda, MD 20892 USA. [Iyengar, Sudha K.] Case Western Reserve Univ, Ophthalmol, Cleveland, OH 44106 USA. RI Mitchell, Paul/P-1498-2014; Wang, Jie Jin/P-1499-2014 OI Wang, Jie Jin/0000-0001-9491-4898 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5816 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891106313 ER PT J AU Kabir, F Jiao, XD Ronchetti, A Gottsch, A Khan, SN Husnain, T Riazuddin, S Sidjanin, DJ Hejtmancik, JF Riazuddin, SA AF Kabir, Firoz Jiao, Xiaodong Ronchetti, Adam Gottsch, Alexander Khan, Shaheen N. Husnain, Tayyab Riazuddin, Sheikh Sidjanin, Duska J. Hejtmancik, J. Fielding Riazuddin, S. Amer TI Autosomal recessive congenital cataracts linked to HSF4 in a consanguineous pedigree SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Kabir, Firoz; Gottsch, Alexander; Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Jiao, Xiaodong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Ronchetti, Adam; Sidjanin, Duska J.] Dept Cell Biol Neurobiol & Anat, Milwaukee, WI USA. [Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh; Riazuddin, S. Amer] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. [Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5598 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891106096 ER PT J AU Kooragayala, K Gotoh, N Li, W Nellissery, J Kaden, TR Covian-Garcia, R Balaban, R Cogliati, T Swaroop, A AF Kooragayala, Keshav Gotoh, Norimoto Li, Wei Nellissery, Jacob Kaden, Talia R. Covian-Garcia, Raul Balaban, Robert Cogliati, Tiziana Swaroop, Anand TI Changes in mitochondria respiration in degenerating mouse retina identified by a novel ex vivo assay SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Kooragayala, Keshav; Li, Wei; Nellissery, Jacob; Kaden, Talia R.; Cogliati, Tiziana; Swaroop, Anand] NEI, NIH, Bethesda, MD 20892 USA. [Gotoh, Norimoto] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. [Li, Wei] NEI, Unit Retinal Neurophysiol, Bethesda, MD 20892 USA. [Covian-Garcia, Raul; Balaban, Robert] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4667 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891104031 ER PT J AU Kutty, RK Samuel, W Nagineni, CN Jaworski, C Duncan, T Vijayasarathy, C Redmond, TM AF Kutty, R. Krishnan Samuel, William Nagineni, Chandrasekharam N. Jaworski, Cynthia Duncan, Todd Vijayasarathy, Camasamudram Redmond, T. Michael TI Proinflammatory Cytokines Induce Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Kutty, R. Krishnan; Samuel, William; Jaworski, Cynthia; Duncan, Todd; Redmond, T. Michael] NEI, LRCMB, NIH, Bethesda, MD 20892 USA. [Nagineni, Chandrasekharam N.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Vijayasarathy, Camasamudram] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4222 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891103012 ER PT J AU Li, W Zhang, YZ Ball, J AF Li, Wei Zhang, Yizhen Ball, John TI Synaptic connections of S-cones in a mammalian retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Li, Wei; Zhang, Yizhen; Ball, John] NEI, Retinal Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4373 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891103161 ER PT J AU Ma, HW Butler, MR Belcher, J Redmond, TM Scanlan, TS Ding, XQ AF Ma, Hongwei Butler, Michael Robert Belcher, Josh Redmond, T. Michael Scanlan, Thomas S. Ding, Xi-Qin TI Inhibition of Thyroid Hormone Receptor Signaling Protects Cones in Mouse Model of Retinal Degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Ma, Hongwei; Butler, Michael Robert; Belcher, Josh; Ding, Xi-Qin] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA. [Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA. [Scanlan, Thomas S.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5474 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891105386 ER PT J AU Minegishi, Y Sheng, XL Ikeo, K Sergeev, YV Iwata, T AF Minegishi, Yuriko Sheng, XunLun Ikeo, Kazuho Sergeev, Yuri V. Iwata, Takeshi TI Novel compound heterozygous mutations of Leber congenital amaurosis in CCT2 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Minegishi, Yuriko; Iwata, Takeshi] Natl Hosp Org, Tokyo Med Ctr, Natl Inst Sensory Organs, Meguro Ku, Tokyo, Japan. [Sheng, XunLun] Ningxia Eye Hosp, Ningxia Peoples Hosp, Ningxia, Peoples R China. [Ikeo, Kazuho] Natl Inst Genet, Lab DNA Data Anal, Shizuoka, Japan. [Sergeev, Yuri V.] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5424 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891105336 ER PT J AU Nair, L AF Nair, Lekha TI Genetic engineering and characterization of Ebi3/CNTF fusokine SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Nair, Lekha] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3497 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891101136 ER PT J AU Nguyen, E Chuang, K Sergeev, YV Badea, T AF Nguyen, Eileen Chuang, Katherine Sergeev, Yuri V. Badea, Tudor TI Identification of heterotypic rox sites for use in novel Dre recombination strategies SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Nguyen, Eileen; Chuang, Katherine; Badea, Tudor] NEI, Retinal Circuit Dev & Genet Unit, Bethesda, MD 20892 USA. [Sergeev, Yuri V.] NEI, OGVFB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4664 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891104028 ER PT J AU Polato, F Notari, L Dong, LJ Becerra, P AF Polato, Federica Notari, Luigi Dong, Lijin Becerra, Patricia TI A conditional knockout mouse for Pnpla2 in photoreceptors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Polato, Federica; Notari, Luigi; Becerra, Patricia] NEI, Sect Prot Struct & Funct, LRCMB, Bethesda, MD 20892 USA. [Dong, Lijin] NEI, Genet Engn Core, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4633 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891103414 ER PT J AU Rocha, EM Zheng, CY Dias, L Nominato, LF Dias, AC AF Rocha, Eduardo M. Zheng, Changyu Dias, Lara Nominato, Luis Fernando Dias, Ana Carolina TI Adenoviral vector-mediated transfer of erythropoietin in the lacrimal gland SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Rocha, Eduardo M.; Dias, Lara; Nominato, Luis Fernando; Dias, Ana Carolina] Univ Sao Paulo, FMRP, Ophthalmol, Ribeirao Preto, Brazil. [Zheng, Changyu] NIDCR, NIH, Bethesda, MD USA. RI Rocha, Eduardo/D-6002-2011 OI Rocha, Eduardo/0000-0001-9888-7313 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3477 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891101116 ER PT J AU Roger, JE Gumerson, JD Braginskaja, E Swaroop, A AF Roger, Jerome E. Gumerson, Jessica D. Braginskaja, Elena Swaroop, Anand TI GSK3 kinases are critical for photoreceptor function and homeostasis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Roger, Jerome E.; Braginskaja, Elena] CERTO CNRS, NeuroPSI, Orsay, France. [Roger, Jerome E.; Gumerson, Jessica D.; Swaroop, Anand] NEI, Neurobiol Neurodegntn Rep Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5527 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891106025 ER PT J AU Samuel, W Kutty, RK Duncan, T Jaworski, C Redmond, TM AF Samuel, William Kutty, R. Krishnan Duncan, Todd Jaworski, Cynthia Redmond, T. Michael TI Regulation of Human Retinal Pigment Epithelial Cell Differentiation by WNT Signal Transduction Pathway SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Samuel, William; Kutty, R. Krishnan; Duncan, Todd; Jaworski, Cynthia; Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4227 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891103017 ER PT J AU Sifuentes, C Kim, JW Yang, HJ Brooks, M Swaroop, A Raymond, P AF Sifuentes, Christopher Kim, Jung-Woong Yang, Hyun-Jin Brooks, Matthew Swaroop, Anand Raymond, Pamela CA RC TI Transcriptional regulation of the Muller glia stem cell response to acute light injury SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Sifuentes, Christopher; Raymond, Pamela] Univ Michigan, Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Kim, Jung-Woong; Yang, Hyun-Jin; Brooks, Matthew; Swaroop, Anand] NEI, Neurodegenerat & Repair, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5486 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891105398 ER PT J AU Song, HM Bush, RA Zeng, Y Vijayasarathy, C Marangoni, D Sieving, PA AF Song, Hongman Bush, Ronald A. Zeng, Yong Vijayasarathy, Camasamudram Marangoni, Dario Sieving, Paul A. TI Constitutively Active RAC1 Causes Photoreceptor Degeneration through NADPH Oxidase-Mediated Oxidative Stress SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Song, Hongman; Bush, Ronald A.; Zeng, Yong; Vijayasarathy, Camasamudram; Marangoni, Dario; Sieving, Paul A.] NIDCD, NIH, Bethesda, MD USA. [Sieving, Paul A.] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5451 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891105363 ER PT J AU Stasheff, SF Nylen, E Hassey, E AF Stasheff, Steven F. Nylen, Erik Hassey, Eric TI Retinal ganglion cell stimulus-response relationships identify pathway-specific alterations for categorization and staging of retinal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Stasheff, Steven F.] NEI, OGVFB, NIH, Bethesda, MD 20892 USA. [Stasheff, Steven F.; Nylen, Erik; Hassey, Eric] Univ Iowa, Pediat Ophthalmol & Vis Sci, Iowa City, IA USA. [Nylen, Erik] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Hassey, Eric] Univ Iowa, Biomed Engn, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4831 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891104189 ER PT J AU Sun, L St Leger, A Yu, CR He, C Mahdi, RM Chan, CC Egwuagu, CE AF Sun, Lin St Leger, Anthony Yu, Chengrong He, Chang Mahdi, Rashid M. Chan, Chi-Chao Egwuagu, Chrales E. TI Interferon regulator factor 8 (IRF-8) limits ocular pathology during HSV-1 infection by restricting the activation and expansion of CD8 T cell SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Sun, Lin; St Leger, Anthony; Yu, Chengrong; He, Chang; Mahdi, Rashid M.; Chan, Chi-Chao; Egwuagu, Chrales E.] NEI, Immunol, Bethesda, MD 20892 USA. RI Sun, Lin/I-3146-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4842 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891104200 ER PT J AU Tan, CY Wandu, W Hinshaw, S Chan, CC Gery, I AF Tan, Cuiyan Wandu, Wambui Hinshaw, Samuel Chan, Chi-Chao Gery, Igal TI Th9-induced conjunctival inflammation: A new animal model for allergic conjunctivitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Tan, Cuiyan; Wandu, Wambui; Hinshaw, Samuel; Chan, Chi-Chao; Gery, Igal] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5871 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891106368 ER PT J AU Veerappan, M Wong, WT Folgar, FA Tai, V Michelson, M Winter, K Stinnett, S Toth, CA AF Veerappan, Malini Wong, Wai T. Folgar, Francisco A. Tai, Vincent Michelson, Michelle Winter, Katrina Stinnett, Sandra Toth, Cynthia A. TI Classification and Correlation of SDOCTv-isualized Drusen Substructures with Drusen Progression in Non-neovascular AMD SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Veerappan, Malini] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA. [Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. [Folgar, Francisco A.; Tai, Vincent; Winter, Katrina; Stinnett, Sandra; Toth, Cynthia A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Michelson, Michelle] Duke Univ, Trinity Coll Arts & Sci, Durham, NC USA. [Toth, Cynthia A.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5139 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891105069 ER PT J AU Vitale, S Clemons, TE Agron, E Ferris, FL Domalpally, A Danis, RP Chew, EY AF Vitale, Susan Clemons, Traci E. Agron, Elvira Ferris, Frederick L. Domalpally, Amitha Danis, Ronald P. Chew, Emily Y. CA AREDS2 Research Grp TI Evaluating the AREDS grading scale for age-related macular degeneration in AREDS2 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Vitale, Susan; Agron, Elvira; Ferris, Frederick L.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Clemons, Traci E.] Emmes Corp, Rockville, MD USA. [Domalpally, Amitha; Danis, Ronald P.] Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3794 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891102006 ER PT J AU West, SK Munoz, BE Weaver, J Mrango, Z Dize, L Gaydos, C Quinn, T Martin, D Zambrano, A AF West, Sheila K. Munoz, Beatriz E. Weaver, Jerusha Mrango, Zakayo Dize, Laura Gaydos, Charlotte Quinn, Thomas Martin, Diana Zambrano, Andrea TI Once Trachoma is gone, what tools can we use for surveillance? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [West, Sheila K.; Munoz, Beatriz E.; Weaver, Jerusha; Zambrano, Andrea] Johns Hopkins Univ, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA. [Mrango, Zakayo] Natl Inst Med Res, Kilosa, Tanzania. [Dize, Laura; Gaydos, Charlotte; Quinn, Thomas] Johns Hopkins Univ, Div Infect Dis, Int Chlamydia Lab, Baltimore, MD USA. [Quinn, Thomas] NIAID, Bethesda, MD 20892 USA. [Martin, Diana] Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 6204 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891107272 ER PT J AU Whitaker, DT Kim, JW Brooks, M Swaroop, A AF Whitaker, Dustin Thad Kim, Jung-Woong Brooks, Matthew Swaroop, Anand TI Defining cell classes in the neural retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Whitaker, Dustin Thad; Kim, Jung-Woong; Brooks, Matthew; Swaroop, Anand] NEI, Bethesda, MD 20892 USA. [Whitaker, Dustin Thad] Texas A&M Univ, Neurosci, College Stn, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5491 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891105403 ER PT J AU Wiley, H Bailey, C Cukras, CA Jaffe, GJ Lee, RWJ Loken, E Meyerle, C Thompson, DJS Wong, WT Ferris, FL AF Wiley, Henry Bailey, Clare Cukras, Catherine A. Jaffe, Glenn J. Lee, Richard W. J. Loken, Erin Meyerle, Catherine Thompson, Darby J. S. Wong, Wai T. Ferris, Frederick L. TI A randomized 36-week crossover trial comparing ranibizumab and bevacizumab for diabetic macular edema SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Wiley, Henry; Cukras, Catherine A.; Wong, Wai T.; Ferris, Frederick L.] NEI, Bethesda, MD 20892 USA. [Bailey, Clare; Lee, Richard W. J.] Univ Hosp Bristol Natl Hlth Serv Fdn Trust, Bristol, Avon, England. [Jaffe, Glenn J.] Duke Reading Ctr, Durham, NC USA. [Lee, Richard W. J.] Moorfields Eye Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, London, England. [Lee, Richard W. J.] UCL, Inst Ophthalmol, London, England. [Loken, Erin; Thompson, Darby J. S.] EMMES Corp, Rockville, MD USA. [Meyerle, Catherine] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21287 USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3149 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891100024 ER PT J AU Yao, XC Zhang, QX Wang, BQ AF Yao, Xincheng Zhang, Qiuxiang Wang, Benquan TI Functional Optical Coherence Tomography of Transient Intrinsic Optical Signal Changes in Retinal Rod and Cone Photoreceptors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Yao, Xincheng; Wang, Benquan] Univ Illinois, Dept Bioengn, Chicago, IL USA. [Yao, Xincheng] Univ Illinois, Dept Ophthalmol & Vis Sci, Chicago, IL USA. [Zhang, Qiuxiang] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 5908 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891106405 ER PT J AU Yeung, J Nair, L Sun, L Egwuagu, C AF Yeung, Justine Nair, Lekha Sun, Lin Egwuagu, Charles TI Genetic engineering and characterization of recombinant mouse IL-27 cytokine SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Yeung, Justine; Nair, Lekha; Sun, Lin; Egwuagu, Charles] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3489 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891101128 ER PT J AU Zambrano, AI Munoz, BE Dize, L Mkocha, H Gaydos, C Quinn, T West, SK AF Zambrano, Andrea Isabela Munoz, Beatriz E. Dize, Laura Mkocha, Harran Gaydos, Charlotte Quinn, Thomas West, Sheila K. TI Measuring Severe Inflammatory Trachoma (TI) when prevalence is low provides indirect data on infection with C. trachomatis in endemic communities SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Zambrano, Andrea Isabela; Dize, Laura; Quinn, Thomas] Johns Hopkins Sch Med, Int Chlamydia Lab, Infect Dis, Baltimore, MD USA. [Munoz, Beatriz E.; West, Sheila K.] Johns Hopkins Univ, Wilmer Eye Inst, Ophthalmol, New York, NY USA. [Mkocha, Harran] Kongwa Trachoma Project, Kongwa, Tanzania. [Gaydos, Charlotte; Quinn, Thomas] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4060 PG 3 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891102261 ER PT J AU Zhang, CX Maminishkis, A Shi, GP Miller, SS AF Zhang, Congxiao Maminishkis, Arvydas Shi, Guangpu Miller, Sheldon S. TI MICRORNA-155 MEDIATES HUMAN RETINAL PIGMENT EPITHELIUM INFLAMMASOME ACTIVITY SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Zhang, Congxiao; Maminishkis, Arvydas; Miller, Sheldon S.] NEI, Sect Epidemiol & Retinal Physiol Dis, Bethesda, MD 20892 USA. [Shi, Guangpu] NEI, Expt Immunol Sect, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 4223 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891103013 ER PT J AU Zhang, LJ Bell, BA Chan, CC Caspi, RR Fung, J Zhang, XM Lin, F AF Zhang, Lingjun Bell, Brent A. Chan, Chi-Chao Caspi, Rachel R. Fung, John Zhang, Xiaomin Lin, Feng TI Deficiency of complement anaphylatoxin receptors leads to ameliorated experimental autoimmune uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Zhang, Lingjun; Bell, Brent A.; Fung, John; Lin, Feng] Cleveland Clin, Cleveland, OH 44106 USA. [Zhang, Lingjun; Zhang, Xiaomin] Tianjing Med Univ, Tianjin, Peoples R China. [Chan, Chi-Chao; Caspi, Rachel R.] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 AR UNSP 3204 PG 2 WC Ophthalmology SC Ophthalmology GA CT5ZY UT WOS:000362891100079 ER PT J AU Moore, KR Cole, SR Dittmer, DP Schoenbach, VJ Smith, JS Baird, DD AF Moore, Kristen R. Cole, Stephen R. Dittmer, Dirk P. Schoenbach, Victor J. Smith, Jennifer S. Baird, Donna D. TI Self-Reported Reproductive Tract Infections and Ultrasound Diagnosed Uterine Fibroids in African-American Women SO JOURNAL OF WOMENS HEALTH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; BACTERIAL VAGINOSIS; YOUNG-WOMEN; RISK; LEIOMYOMATA; PREVALENCE; EPIDEMIOLOGY; ASSOCIATION; ALCOHOL; HISTORY AB Background: For decades, it has been hypothesized that reproductive tract infections (RTIs) are risk factors for uterine fibroids. However, only two recent studies have been conducted. We aimed to investigate the relationship between RTIs and fibroids in a large study using ultrasound screening for fibroids. Methods: We used cross-sectional enrollment data from African American women ages 23-34 years with no previous fibroid diagnosis. RTI history was measured by self-report and fibroid status by standardized ultrasound. Secondary fibroid outcomes were size, number, and total volume. Age- and multivariable-adjusted logistic regression were used to estimate odds ratios (ORs). Results: In total, 1,656 women were included; 22% had fibroids. Bacterial vaginosis (BV) was associated with a 21% increased odds of fibroids [aOR 1.21, 95% confidence interval (CI) 0.93-1.58]. Chlamydia infection and pelvic inflammatory disease were associated with a 38% (aOR 0.62, 95% CI 0.40-0.97) and a 46% (aOR 0.54, 95% CI 0.25-1.17) reduced odds of having two or more fibroids, respectively. Those with a previous BV diagnosis had a 47% increased odds of having 2 or more fibroids (aOR 1.47, 95% CI 0.98-2.21) and a 41% increased odds of having a larger total fibroid volume (aOR 1.41, 95% CI 0.98-2.04). Conclusions: Our study was the first to explore the relationship between RTIs and fibroid size, number, and total volume. There appeared to be no strong associations between self-reported RTIs and fibroids. Studies using serology, a biochemical measure of past infection, are needed to better investigate associations between RTIs and fibroids. C1 [Moore, Kristen R.; Cole, Stephen R.; Schoenbach, Victor J.; Smith, Jennifer S.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Dittmer, Dirk P.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Microbiol & Immunol, Program Global Oncol, Chapel Hill, NC 27599 USA. [Moore, Kristen R.; Baird, Donna D.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Baird, DD (reprint author), NIEHS, Epidemiol Branch A3 05, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM baird@niehs.nih.gov RI Moore, Kristen/C-2303-2017; Baird, Donna/D-5214-2017 OI Moore, Kristen/0000-0001-9993-3270; Baird, Donna/0000-0002-5544-2653 FU NIH, National Institute of Environmental Health Sciences [10-E-N044]; American Recovery and Reinvestment Act funds FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (10-E-N044). Funding also came from the American Recovery and Reinvestment Act funds designated for National Institute of Health research. NR 38 TC 3 Z9 5 U1 0 U2 1 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 JUN 1 PY 2015 VL 24 IS 6 BP 489 EP 495 DI 10.1089/jwh.2014.5051 PG 7 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 CU9OP UT WOS:000363874300005 PM 25901468 ER PT J AU Ardeljan, C Chan, CC Abu-Asab, MS AF Ardeljan, Christopher Chan, Chi-Chao Abu-Asab, Mones S. TI State of Retinal and Choroidal Capillaries in Murine AMD Mouse Models: A Comparative Study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Ardeljan, Christopher; Chan, Chi-Chao; Abu-Asab, Mones S.] NEI, Immunol Lab, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205328 ER PT J AU Blenkinsop, TA Saini, JS Maminishkis, A Bharti, K Wan, Q Davis, J Miller, SS Temple, S Stern, J AF Blenkinsop, Timothy A. Saini, Janmeet S. Maminishkis, Arvydas Bharti, Kapil Wan, Qin Davis, Janine Miller, Sheldon S. Temple, Sally Stern, Jeffrey TI Human Adult Retinal Pigment Epithelial Cultures Exhibit Key Physiological Characteristics of Native RPE Tissue SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Blenkinsop, Timothy A.] Icahn Sch Med Mt Sinai, Dev & Regenerat Biol, New York, NY 10029 USA. [Saini, Janmeet S.; Temple, Sally; Stern, Jeffrey] Neural Stem Cell Inst, Rensselaer, NY USA. [Maminishkis, Arvydas; Bharti, Kapil; Wan, Qin; Davis, Janine; Miller, Sheldon S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2330 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205331 ER PT J AU Bonilha, VL Rayborn, ME Shadrach, KG Hollyfield, JG Maminishkis, A Miller, SS AF Bonilha, Vera L. Rayborn, Mary E. Shadrach, Karen G. Hollyfield, Joe G. Maminishkis, Arvydas Miller, Sheldon S. TI DJ-1 Levels Alter Autophagy in the Retinal Pigment Epithelium (RPE) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Bonilha, Vera L.; Rayborn, Mary E.; Shadrach, Karen G.; Hollyfield, Joe G.] Cleveland Clin, Lerner Ctr, Cole Eye Inst, Ophthalmol, Cleveland, OH 44106 USA. [Maminishkis, Arvydas; Miller, Sheldon S.] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2408 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205409 ER PT J AU Boobalan, E Alur, RP Dong, LJ Shih, G Onojafe, IF Memon, O Bharti, K Brooks, BP AF Boobalan, Elangovan Alur, Ramakrishna Prasad Dong, Lijin Shih, Grace Onojafe, Ighovie Felix Memon, Omar Bharti, Kapil Brooks, Brian P. TI Loss of Nlz2 Expression Results in Coloboma and Abnormal RPE Development in Mouse SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Boobalan, Elangovan; Alur, Ramakrishna Prasad; Shih, Grace; Onojafe, Ighovie Felix; Brooks, Brian P.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Dong, Lijin] NEI, GENET ENGN CORE, Bethesda, MD 20892 USA. [Memon, Omar] NEI, SECT EPITHELIAL & RETINAL PHYSIOL & DIS, Bethesda, MD 20892 USA. [Bharti, Kapil] NEI, OCULAR & STEM CELL TRANSLAT RES UNIT, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1484 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882203374 ER PT J AU Bullock, J Polato, F Becerra, P AF Bullock, Jeanee Polato, Federica Becerra, Patricia TI PEDF Alterations that Modify Receptor Affinity: Implications for the construction of PEDF with optimal biological effects SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Bullock, Jeanee; Polato, Federica; Becerra, Patricia] NEI, Sect Prot Struct & Funct, NIH, Bethesda, MD 20892 USA. [Bullock, Jeanee] Georgetown Univ, Med Ctr, Biochem & Mol & Cellular Biol, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 804 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202141 ER PT J AU Chew, EY Clemons, TE Agron, E Martin, DF Bressler, SB Gensler, G Wiley, H AF Chew, Emily Y. Clemons, Traci E. Agron, Elvira Martin, Daniel F. Bressler, Susan B. Gensler, Gary Wiley, Henry CA Age-Related Eye Dis Study Res Grp TI The Lack of Progression of Age-Related Macular Degeneration following Cataract Surgery in the Age-Related Eye Disease Study 2 (AREDS2) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Chew, Emily Y.; Agron, Elvira; Wiley, Henry] NEI, Bethesda, MD 20892 USA. [Clemons, Traci E.; Gensler, Gary] EMMES Corp, Rockville, MD USA. [Martin, Daniel F.] Cole Eye Inst, Cleveland, OH USA. [Bressler, Susan B.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2572 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882206141 ER PT J AU Clemons, TE Chew, EY Peto, T Sallo, F AF Clemons, Traci E. Chew, Emily Y. Peto, Tunde Sallo, Ferenc CA MacTel Study Grp TI Responsiveness and the minimal clinically important difference for the NEI VFQ-25 in patients with Macular Telangectasia Type 2 (MacTel Type 2) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Clemons, Traci E.] EMMES Corp, Rockville, MD USA. [Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA. [Sallo, Ferenc; MacTel Study Grp] Moorfields Eye Hosp, NIHR BMRC, London, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1360 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882203251 ER PT J AU Clore-Gronenborn, K Miyagishima, K Zhang, CX Rajan, V Silver, J Wan, Q Sharma, R Cukras, CA Miller, SS Bharti, K AF Clore-Gronenborn, Katharina Miyagishima, Kiyoharu Zhang, Congxiao Rajan, Vaisakh Silver, Jason Wan, Qin Sharma, Ruchi Cukras, Catherine A. Miller, Sheldon S. Bharti, Kapil TI Modeling Late-Onset Retinal Degeneration with Human iPSCs: Insights into the Shared Pathogenesis of Macular Degenerations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Clore-Gronenborn, Katharina; Rajan, Vaisakh; Silver, Jason; Sharma, Ruchi; Bharti, Kapil] NEI, Unit Ocular Stem Cell & Translat Res, NIH, Bethesda, MD 20892 USA. [Miyagishima, Kiyoharu; Zhang, Congxiao; Wan, Qin; Miller, Sheldon S.] NEI, Sect Epithelial & Retinal Physiol & Dis, NIH, Bethesda, MD 20892 USA. [Cukras, Catherine A.] NEI, Clin Trials Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2379 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205380 ER PT J AU Guedez, L Popp, N Shen, DF Qian, HH Li, YC Chan, CC AF Guedez, Liliana Popp, Nicholas Shen, DeFen Qian, Haohua Li, Yichao Chan, Chi-Chao TI Antibiotic Treatment Exacerbates Focal Retinal Degeneration in a Mouse Model of AMD SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Guedez, Liliana; Popp, Nicholas; Shen, DeFen; Chan, Chi-Chao] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Qian, Haohua; Li, Yichao] NEI, Visual Funct Core, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 276 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882201035 ER PT J AU Hannes, S Liu, BY Li, ZY Ling, D Sen, HN Nussenblatt, RB AF Hannes, Susan Liu, Baoying Li, Zhiyu Ling, Diamond Sen, H. Nida Nussenblatt, Robert B. TI Peripheral Monocyte Subset-Derived Macrophages Show Distinct Expression Kinetics of Immune Biomarkers Associated with Ocular Autoimmunity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Hannes, Susan; Liu, Baoying; Li, Zhiyu; Ling, Diamond; Sen, H. Nida; Nussenblatt, Robert B.] NEI, Clin Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 884 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202221 ER PT J AU He, C Yu, CR Sun, L Mahdi, RM Yeung, J Egwuagu, CE AF He, Chang Yu, Chengrong Sun, Lin Mahdi, Rashid M. Yeung, Justine Egwuagu, Chrales E. TI SOCS1-Mimetic Eye-drops inhibit ocular inflammation and protect against ocular pathology during Experimental Autoimmune Uveitis (EAU) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [He, Chang; Yu, Chengrong; Sun, Lin; Mahdi, Rashid M.; Yeung, Justine; Egwuagu, Chrales E.] NEI, NIH, Bethesda, MD 20892 USA. RI Sun, Lin/I-3146-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3098 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882207260 ER PT J AU Hinshaw, S Wandu, WW Shi, GP Yang, JF Gery, I AF Hinshaw, Samuel Wandu, Wambul (Sylvia) Wambul Shi, Guangpu Yang, Jianfei Gery, Igal TI TMP778 Inhibits Induction of Experimental Autoimmune Uveitis and related immune responses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Hinshaw, Samuel; Wandu, Wambul (Sylvia) Wambul; Shi, Guangpu; Gery, Igal] NEI, NIH, Bethesda, MD 20892 USA. [Yang, Jianfei] Tempero Pharmaceut GSK, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 851 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202188 ER PT J AU Jiao, XD Kabir, F Khan, A Wang, QW Li, D Khan, SN Husnain, T Riazuddin, S Hejtmancik, JF Riazuddin, SA AF Jiao, Xiaodong Kabir, Firoz Khan, Arif Wang, Qiwei Li, David Khan, Shaheen N. Husnain, Tayyab Riazuddin, Sheikh Hejtmancik, J. Fielding Riazuddin, S. Amer TI A common ancestral mutation in CRYBB3 identified in multiple consanguineous pedigrees with congenital cataracts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Jiao, Xiaodong; Wang, Qiwei; Li, David; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Kabir, Firoz; Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Khan, Arif] King Khalid Eye Specialist Hosp, Div Pediat Ophthalmol, Riyadh, Saudi Arabia. [Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh; Riazuddin, S. Amer] Univ Punjab, Natl Ctr Excellence Moloecular Biol, Lahore, Pakistan. [Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2527 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882206112 ER PT J AU Kadmiel, M Ramamoorthy, S Cidlowski, J AF Kadmiel, Mahita Ramamoorthy, Sivapriya Cidlowski, John TI Glucocorticoid Receptor Role in the Mouse Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Kadmiel, Mahita; Ramamoorthy, Sivapriya; Cidlowski, John] NIEHS, NIH, Durham, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 887 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202224 ER PT J AU Kaya, KD Brooks, M Yang, HJ Kim, JW Karakulah, G Swaroop, A AF Kaya, Koray Dogan Brooks, Matthew Yang, Hyun-Jin Kim, Jung-Woong Karakulah, Gokhan Swaroop, Anand TI RetSeq: Next Generation Sequencing Database for Exploring Retinal Development, Aging and Disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Kaya, Koray Dogan; Brooks, Matthew; Yang, Hyun-Jin; Kim, Jung-Woong; Karakulah, Gokhan; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1240 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882203149 ER PT J AU Khristov, V Hartford, J Wan, Q Lotfi, MR Miyagishima, K Hotaling, N Maminishkis, A Amaral, J Miller, SS Bharti, K AF Khristov, Vladimir Hartford, Juliet Wan, Qin Lotfi, Mostafa Reza Miyagishima, Kiyoharu Hotaling, Nathan Maminishkis, Arvydas Amaral, Juan Miller, Sheldon S. Bharti, Kapil TI Developing iPS Cell Derived RPE Tissue for Clinical Application SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Khristov, Vladimir; Hartford, Juliet; Wan, Qin; Lotfi, Mostafa Reza; Miyagishima, Kiyoharu; Maminishkis, Arvydas; Amaral, Juan; Miller, Sheldon S.; Bharti, Kapil] NEI, NIH, Bethesda, MD 20892 USA. [Hotaling, Nathan] NIST, Biosyst & Biomat Div, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1834 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882204282 ER PT J AU Kim, JS Jaworski, L Kaushal, P Vitale, S Knickelbein, JE Nussenblatt, RB Sen, HN AF Kim, Jane S. Jaworski, Laurence Kaushal, Padmini Vitale, Susan Knickelbein, Jared E. Nussenblatt, Robert B. Sen, H. Nida TI Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) in Uveitis: An Intra-Session and Inter-Observer Reproducibility Study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Kim, Jane S.; Jaworski, Laurence; Kaushal, Padmini; Vitale, Susan; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1722 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882204172 ER PT J AU Knickelbein, JE Hannes, S Liu, BY Arakelyan, A Grivel, JC Maminishkis, A Sen, HN Miller, SS Margolis, L Nussenblatt, RB AF Knickelbein, Jared E. Hannes, Susan Liu, Baoying Arakelyan, Anush Grivel, Jean Charles Maminishkis, Arvydas Sen, H. Nida Miller, Sheldon S. Margolis, Leonid Nussenblatt, Robert B. TI Modulation of monocyte activation by retinal pigment epithelium (RPE)-derived exosomes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Knickelbein, Jared E.; Hannes, Susan; Liu, Baoying; Sen, H. Nida; Nussenblatt, Robert B.] NEI, Immunol Lab, Rockville, MD USA. [Arakelyan, Anush; Grivel, Jean Charles; Margolis, Leonid] NICHHD, Sect Intercellular Interact, Bethesda, MD 20892 USA. [Maminishkis, Arvydas; Miller, Sheldon S.] NEI, Sect Epithelial & Retinal Physiol & Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 3102 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882207264 ER PT J AU Lee, EJ Brown, B Vance, E Hazard, R Silver, P Caspi, RR Rosenzweig, HL AF Lee, Ellen J. Brown, Brieanna Vance, Emily Hazard, Riley Silver, Phyllis Caspi, Rachel R. Rosenzweig, Holly Lallman TI Identification of the vital role of the innate receptor Mincle in the pathogenesis of autoimmune uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Lee, Ellen J.; Brown, Brieanna; Vance, Emily; Rosenzweig, Holly Lallman] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lee, Ellen J.; Brown, Brieanna; Vance, Emily; Hazard, Riley; Rosenzweig, Holly Lallman] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. [Silver, Phyllis; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 879 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202216 ER PT J AU Lee, JW Huang, JD Rodriguez, IR AF Lee, Jung W. Huang, Jiahn-Dar Rodriguez, Ignacio R. TI Metabolism of 7-ketocholesterol in ARPE-19 cells occurs by esterification to fatty acids via cPLA2 alpha/SOAT1 followed by selective efflux to HDL SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Lee, Jung W.; Huang, Jiahn-Dar; Rodriguez, Ignacio R.] NEI, Mech Retinal Dis Sect, LRCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1532 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882203422 ER PT J AU Li, YC Fariss, RN Cohen, ED Qian, HH AF Li, Yichao Fariss, Robert N. Cohen, Ethan D. Qian, Haohua TI Light-induced thickening of photoreceptor outer segment layer detected by ultrahigh resolution OCT imaging SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Li, Yichao; Qian, Haohua] NEI, Visual Funct Core, NIH, Rockville, MD USA. [Fariss, Robert N.] NEI, Biol Imaging core, NIH, Rockville, MD USA. [Cohen, Ethan D.] US FDA, Div Biomed Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1307 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882203209 ER PT J AU Liu, BY Li, ZY Silver, P Tan, CY Chen, P Chan, CC Nussenblatt, RB AF Liu, Baoying Li, Zhiyu Silver, Phyllis Tan, Cuiyan Chen, Ping Chan, Chi-Chao Nussenblatt, Robert B. TI Effect of HDACi Givinostat in Treating Experimental Ocular Autoimmunity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Liu, Baoying; Li, Zhiyu; Silver, Phyllis; Tan, Cuiyan; Chen, Ping; Chan, Chi-Chao; Nussenblatt, Robert B.] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 882 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202219 ER PT J AU Marangoni, D Vijayasarathy, C Bush, RA Wei, LS Wen, R Sieving, PA AF Marangoni, Dario Vijayasarathy, Camasamudram Bush, Ronald A. Wei, Lisa Wen, Rong Sieving, Paul A. TI Intravitreal CNTF transiently improves residual cone function in CNGB3 mouse SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Marangoni, Dario; Vijayasarathy, Camasamudram; Bush, Ronald A.; Sieving, Paul A.] NIDCD, NIH, Bethesda, MD USA. [Wei, Lisa; Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. [Wen, Rong] Univ Miami, Bascon Palmer Eye Inst, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 479 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882201237 ER PT J AU Martinez, AM Khristov, V Li, A Sharma, R Memon, O Riordon, D Gundry, R Boheler, K Miller, SS Bharti, K AF Martinez, Alejandro Morales Khristov, Vladimir Li, Andrea Sharma, Ruchi Memon, Omar Riordon, Daniel Gundry, Rebekah Boheler, Kenneth Miller, Sheldon S. Bharti, Kapil TI Identification of Surface Proteome for Human Retinal Pigment Epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Martinez, Alejandro Morales; Khristov, Vladimir; Li, Andrea; Sharma, Ruchi; Memon, Omar; Miller, Sheldon S.; Bharti, Kapil] NEI, NIH, Bethesda, MD 20892 USA. [Riordon, Daniel] NIA, NIH, Bethesda, MD 20892 USA. [Gundry, Rebekah] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Boheler, Kenneth] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2336 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205337 ER PT J AU Meguro, A Mok, J Takeuchi, M Ishioka, M Iwasaki, M Fukagawa, K Konomi, K Shimazaki, J Joo, CK Mizuki, N AF Meguro, Akira Mok, Jeewon Takeuchi, Masaki Ishioka, Misaki Iwasaki, Miki Fukagawa, Kazumi Konomi, Kenji Shimazaki, Jun Joo, Choun-Ki Mizuki, Nobuhisa TI Replication study of previous keratoconus genome-wide association study findings in East Asian populations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Meguro, Akira; Takeuchi, Masaki; Ishioka, Misaki; Mizuki, Nobuhisa] Yokohama City Univ, Sch Med, Dept Ophthalmol, Yokohama, Kanagawa 232, Japan. [Mok, Jeewon; Joo, Choun-Ki] Catholic Univ Korea, Catholic Inst Visual Sci, Seoul, South Korea. [Takeuchi, Masaki] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Ishioka, Misaki; Iwasaki, Miki; Fukagawa, Kazumi] Ryogoku Eye Clin, Sumida Ku, Tokyo, Japan. [Konomi, Kenji; Shimazaki, Jun] Ichikawa Gen Hosp, Tokyo Dent Coll, Dept Ophthalmol, Ichikawa, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2513 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882206098 ER PT J AU Menard, C SanGiovanni, JPP De Guire, V Sapieha, PM AF Menard, Catherine SanGiovanni, John Paul P. De Guire, Vincent Sapieha, Przemyslaw Mike TI Micro-RNA signatures in the vitreous and plasma of patients suffering from exudative AMD SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Menard, Catherine] Univ Montreal, Biochim, Montreal, PQ, Canada. [SanGiovanni, John Paul P.] NEI, NIH, Bethesda, MD 20892 USA. [De Guire, Vincent] Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. [Sapieha, Przemyslaw Mike] Univ Montreal, Ophtalmol, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 809 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202146 ER PT J AU Mookherjee, S Hiriyanna, S Kaneshiro, K Qian, HH Li, TS Khanna, H Colosi, P Swaroop, A Wu, ZJ AF Mookherjee, Suddhasil Hiriyanna, Suja Kaneshiro, Kayleigh Qian, Haohua Li, Tiansen Khanna, Hemant Colosi, Peter Swaroop, Anand Wu, Zhijian TI Gene therapy rescues cone function and viability in Rp2 knockout mice over a broad vector dose range and a wide therapeutic time window SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Mookherjee, Suddhasil; Hiriyanna, Suja; Colosi, Peter; Wu, Zhijian] NEI, Ocular Gene Therapy Unit, NIH, Bethesda, MD 20892 USA. [Kaneshiro, Kayleigh] Univ Calif, Irvine Sch Med, Irvin, CA USA. [Qian, Haohua; Li, Tiansen; Swaroop, Anand] NEI, NNRL, NIH, Bethesda, MD 20892 USA. [Khanna, Hemant] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2063 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205079 ER PT J AU Nowosielski, Y Humpel, C Gramlich, O Cawley, N Loh, P Troger, J Bechrakis, N AF Nowosielski, Yvonne Humpel, Christian Gramlich, Oliver Cawley, Niamh Loh, Peng Troger, Josef Bechrakis, Nikolaos CA Med Univ Innsbruck TI Serpinin in the rat eye SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Nowosielski, Yvonne; Troger, Josef; Bechrakis, Nikolaos] Med Univ Innsbruck, Ophthalmol & Optometry, A-6020 Innsbruck, Austria. [Humpel, Christian] Med Univ Innsbruck, Dept Psychiat, Lab Psychiat & Expt Alzheimers Res, A-6020 Innsbruck, Austria. [Gramlich, Oliver] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 62242 USA. [Gramlich, Oliver] Univ Iowa, Stephen A Wynn Inst Vis Res, Iowa City, IA 62242 USA. [Cawley, Niamh; Loh, Peng] Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1541 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882204002 ER PT J AU O'Brien, J Kothmann, WW Wang, YR AF O'Brien, John Kothmann, W. Wade Wang, Yanran TI Rapid light-driven regulation of Connexin35 phosphorylation in zebrafish retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [O'Brien, John; Kothmann, W. Wade; Wang, Yanran] Univ Texas Houston, Sch Med, Ophthal & Visual Sci, Houston, TX USA. [Kothmann, W. Wade] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2249 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205250 ER PT J AU Onojafe, IF Qian, HH Miyagishima, K Zhang, CX Miller, SS Brooks, BP AF Onojafe, Ighovie Felix Qian, Haohua Miyagishima, Kiyoharu Zhang, Congxiao Miller, Sheldon S. Brooks, Brian Patrick CA NEI TI Visual function and Nitisinone treatment in a mouse model of OCA1b (Tyr-(c-h/c-h)) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Onojafe, Ighovie Felix; Brooks, Brian Patrick] NEI, OGVFB, NIH, Bethesda, MD 20892 USA. [Qian, Haohua] NEI, Visual Funct Core, Bethesda, MD 20892 USA. [Miyagishima, Kiyoharu; Zhang, Congxiao; Miller, Sheldon S.] NEI, Sect Epithelial & Retinal Physiol & Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1487 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882203377 ER PT J AU Patterson, SS Nelson, RF AF Patterson, Sara Stokes Nelson, Ralph F. TI Spectral properties of a zebrafish transgenic with L-opsin expression in all cone types SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Patterson, Sara Stokes; Nelson, Ralph F.] NINDS, Basic Neurosci Program, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 994 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202315 ER PT J AU Peto, T Clemons, TE Chew, EY Leung, I Sallo, F Bird, AC AF Peto, Tunde Clemons, Traci E. Chew, Emily Y. Leung, Irene Sallo, Ferenc Bird, Alan C. CA MacTel Study Grp TI 36-months follow-up of the Phase 1 clinical trial of the use ciliary neurotrophic factor (CNTF) for Macular Telangiectasia Type 2 (MacTel) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Peto, Tunde; Leung, Irene; Sallo, Ferenc; Bird, Alan C.] NIHR Biomed Rsrch Ctr Ophthalmol, MEH & IoO, London, England. [Clemons, Traci E.] EMMES Corp, Rockdale, MD USA. [Chew, Emily Y.] NEI, Rockdale, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1815 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882204263 ER PT J AU Popp, N Wang, V Tuo, JS Li, YC Qian, HH Ardeljan, C Abu-Asab, MS Ribeiro, J Francischetti, I Chan, CC AF Popp, Nicholas Wang, Vinson Tuo, Jingsheng Li, Yichao Qian, Haohua Ardeljan, Christopher Abu-Asab, Mones S. Ribeiro, Jose Francischetti, Ivo Chan, Chi-Chao TI Inhibition of Tissue Factor by Ixolaris in Models of Age-Related Macular Degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Popp, Nicholas; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Vinson] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Li, Yichao; Qian, Haohua] NIH, Visual Funct Core, Bethesda, MD 20892 USA. [Ardeljan, Christopher; Abu-Asab, Mones S.] NEI, Histol Core, NIH, Bethesda, MD 20892 USA. [Ribeiro, Jose; Francischetti, Ivo] NIAID, Lab Malaria & Vector Biol, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205284 ER PT J AU Priya, RR Perez, S Mutsuddi, M Chaitankar, V Othman, M Heckenlively, J Branham, K Swaroop, A AF Priya, Rinki Ratna Perez, Samuel Mutsuddi, Mousumi Chaitankar, Vijender Othman, Mohammad Heckenlively, John Branham, Kari Swaroop, Anand TI Whole exome sequencing reveals novel pathways implicated in age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Priya, Rinki Ratna; Perez, Samuel; Chaitankar, Vijender; Swaroop, Anand] NEI, N NRL, NIH, Bethesda, MD 20892 USA. [Mutsuddi, Mousumi] Banaras Hindu Univ, Dept Mol & Human Genet, Varanasi 221005, Uttar Pradesh, India. [Othman, Mohammad; Heckenlively, John; Branham, Kari] Univ Michigan, Dept Ophthalmol, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 789 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202126 ER PT J AU Quinn, TP Nussenblatt, RB Liu, BY AF Quinn, Timothy Powers Nussenblatt, Robert B. Liu, Baoying TI The Effect of HDACi Givinostat on the Expression of Immune Markers Related to Human Ocular Inflammation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Quinn, Timothy Powers] Wayne State Univ, Sch Med, Grosse Pointe Pk, MI USA. [Quinn, Timothy Powers; Nussenblatt, Robert B.; Liu, Baoying] NEI, Clin Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 883 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202220 ER PT J AU Rao, SR Pfeffer, BA Choi, M Francis, K Porter, FD Fliesler, SJ AF Rao, Sriganesh Ramachandra Pfeffer, Bruce A. Choi, Meerim Francis, Kevin Porter, Forbes D. Fliesler, Steven J. TI Understanding the molecular mechanism of RPE pathology in Smith-Lemli-Opitz Syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Rao, Sriganesh Ramachandra; Pfeffer, Bruce A.; Choi, Meerim; Fliesler, Steven J.] SUNY Buffalo, Ophthalmol & Biochem, Buffalo, NY 14260 USA. [Rao, Sriganesh Ramachandra; Pfeffer, Bruce A.; Choi, Meerim; Fliesler, Steven J.] SUNY Eye Inst, Buffalo, NY USA. [Rao, Sriganesh Ramachandra; Pfeffer, Bruce A.; Choi, Meerim; Fliesler, Steven J.] VA Western NY Healthcare Syst, Res Serv, Buffalo, NY USA. [Francis, Kevin; Porter, Forbes D.] NICHD, PDEGEN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2389 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205390 ER PT J AU Ruchi, F Davis, J Jha, BSS Khristov, V Hartford, J Hua, F Wan, Q Bharti, K AF Ruchi, Fnu Davis, Janine Jha, Balendu Shekhar Shekhar Khristov, Vladimir Hartford, Juliet Hua, Fang Wan, Qin Bharti, Kapil TI A Tri-phasic Developmentally Guided Differentiation Protocol for Efficient Generation of Functional Retinal Pigment Epithelium from Induced Pluripotent Stem Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Ruchi, Fnu; Davis, Janine; Jha, Balendu Shekhar Shekhar; Khristov, Vladimir; Hartford, Juliet; Hua, Fang; Wan, Qin; Bharti, Kapil] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1841 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882204289 ER PT J AU Sallo, FB Leung, I Rocco, V Zeimer, M Heimes, B Clemons, TE Pauleikhoff, D Chew, EY Bird, AC Peto, T AF Sallo, Ferenc B. Leung, Irene Rocco, Vincent Zeimer, Meike Heimes, Britta Clemons, Traci E. Pauleikhoff, Daniel Chew, Emily Y. Bird, Alan C. Peto, Tunde CA MacTel Study Grp TI Three-dimensional characteristics of outer retinal atrophy in type 2 idiopathic macular telangiectasia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Sallo, Ferenc B.] UCL Inst Ophthalmol, Visual Neurosci, London, England. [Sallo, Ferenc B.; Leung, Irene; Rocco, Vincent] Moorfields Eye Hosp, Res & Dev, London, England. [Zeimer, Meike; Heimes, Britta; Pauleikhoff, Daniel] St Franziskus Hosp, Dept Ophthalmol, Munster, Germany. [Clemons, Traci E.] EMMES Corp, Rockville, MD USA. [Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA. [Bird, Alan C.] Moorfields Eye Hosp, Inherited Eye Dis, London, England. [Peto, Tunde] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr Ophthalmol, London, England. [Peto, Tunde] UCL Inst Ophthalmol, London, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2783 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882206353 ER PT J AU Sergeev, YV Pogrebniak, K Fujinami, K Falsini, B Zein, WM Goetz, KE Jayasundera, T Michaelides, M Brooks, BP Sieving, PA AF Sergeev, Yuri V. Pogrebniak, Katherine Fujinami, Kaoru Falsini, Benedetto Zein, Wadih M. Goetz, Kerry E. Jayasundera, Thiran Michaelides, Michel Brooks, Brian Patrick Sieving, Paul A. TI Stargardt ABCA4 mutation analysis in trans-membrane and nucleotide-binding domains SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Sergeev, Yuri V.; Pogrebniak, Katherine; Falsini, Benedetto; Zein, Wadih M.; Goetz, Kerry E.; Brooks, Brian Patrick; Sieving, Paul A.] NEI, OGVFB, Bethesda, MD 20892 USA. [Fujinami, Kaoru] Natl Inst Sensory Organs, Tokyo, Japan. [Jayasundera, Thiran] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. [Michaelides, Michel] Moorfields Eye Hosp, London, England. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2860 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882207024 ER PT J AU Si, H Urzua, CA Liu, BY Li, ZY Sura, A Lee, A Nussenblatt, RB AF Si, Han Urzua, Cristhian A. Liu, Baoying Li, Zhiyu Sura, Amol Lee, Adrianna Nussenblatt, Robert B. TI Whole transcriptome profiling of peripheral CD4(+) T-cells in age-related macular degeneration patients using RNA-seq SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Si, Han; Urzua, Cristhian A.; Liu, Baoying; Li, Zhiyu; Sura, Amol; Lee, Adrianna; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 820 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202157 ER PT J AU Sieving, PC Prakash, GJ AF Sieving, Pamela C. Prakash, Gyan John TI Global Impact of NEI Funding: Research Directions and Potential Collaborations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 [Prakash, Gyan John] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2135 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205137 ER PT J AU Stoddard, J Bharti, K Bonnah, R Tippner-Hedges, R McGill, TJ Ma, H Mitalipov, S Neuringer, M AF Stoddard, Jonathan Bharti, Kapil Bonnah, Robert Tippner-Hedges, Rebecca McGill, Trevor J. Ma, Hong Mitalipov, Shoukhrat Neuringer, Martha TI Improving the efficiency of RPE cell differentiation from rhesus macaque iPS- and SCNT-derived stem cell lines SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Stoddard, Jonathan; Bonnah, Robert; Tippner-Hedges, Rebecca; McGill, Trevor J.; Ma, Hong; Mitalipov, Shoukhrat; Neuringer, Martha] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Bharti, Kapil] NEI, NIH, Bethesda, MD 20892 USA. [McGill, Trevor J.; Neuringer, Martha] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1844 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882204292 ER PT J AU Sura, A Liu, BY Li, ZY Hannes, S Gordon, S Nussenblatt, RB AF Sura, Amol Liu, Baoying Li, Zhiyu Hannes, Susan Gordon, Siamon Nussenblatt, Robert B. TI Expression of MSR-1-a Class-A Macrophage Scavenger Receptor-May Be Altered in Ocular Sarcoidosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Sura, Amol; Liu, Baoying; Li, Zhiyu; Hannes, Susan; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. [Sura, Amol] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Gordon, Siamon] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 854 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202191 ER PT J AU Thavikulwat, A Jacobs-El, N Hasan, J Valent, D Cukras, CA Wiley, H Wong, WT Chew, EY AF Thavikulwat, Alisa Jacobs-El, Naima Hasan, Jesia Valent, David Cukras, Catherine A. Wiley, Henry Wong, Wai T. Chew, Emily Y. TI Evolution of Geographic Atrophy in Patients Treated with Ranibizumab for Neovascular Age-related Macular Degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Thavikulwat, Alisa] Univ Rochester, Sch Med, Bethesda, MD USA. [Thavikulwat, Alisa; Jacobs-El, Naima; Hasan, Jesia; Valent, David; Cukras, Catherine A.; Wiley, Henry; Wong, Wai T.; Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202228 ER PT J AU Tomarev, SI Kwon, HS Jaworski, C Yang, IH AF Tomarev, Stanislav I. Kwon, Heung Sun Jaworski, Cynthia Yang, In Hong TI Myocilin protects axons from myelin-associated glycoprotein-induced degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Tomarev, Stanislav I.; Kwon, Heung Sun] NEI, SRGCB, LRCMB, NIH, Bethesda, MD 20892 USA. [Jaworski, Cynthia] NEI, LRCMB, NIH, Bethesda, MD 20892 USA. [Yang, In Hong] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2410 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205410 ER PT J AU Tumminia, SJ Blain, D Cooper, RC Garafalo, AV Iano-Fletcher, J Parrish, RS Reeves, MJ Yim, A Goetz, KE AF Tumminia, Santa J. Blain, Delphine Cooper, Remy C. Garafalo, Alexandra V. Iano-Fletcher, Jemma Parrish, Rebecca S. Reeves, Melissa J. Yim, Annette Goetz, Kerry E. TI eyeGENE (R) : a cross-cutting international inherited eye disease clinical research network SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Tumminia, Santa J.] NEI, Off Director, NIH, Bethesda, MD 20892 USA. [Blain, Delphine; Cooper, Remy C.; Garafalo, Alexandra V.; Iano-Fletcher, Jemma; Parrish, Rebecca S.; Reeves, Melissa J.; Yim, Annette; Goetz, Kerry E.] NEI, Ophthalm Genet Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1250 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882203159 ER PT J AU Urzua, CA Si, H Liu, BY Lait, P Lee, RWJ Goecke, A Nussenblatt, RB AF Urzua, Cristhian A. Si, Han Liu, Baoying Lait, Philippa Lee, Richard W. J. Goecke, Annelise Nussenblatt, Robert B. TI Expression kinetics of Glucocorticoid Receptor lsoforms Predicts Treatment Response to Glucocorticoids in Uveitis patients SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Urzua, Cristhian A.] Univ Chile, Ophthalmol, Santiago, Chile. [Urzua, Cristhian A.; Si, Han; Liu, Baoying; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Lait, Philippa; Lee, Richard W. J.] Univ Bristol, Sch clin Sci, Bristol, Avon, England. [Goecke, Annelise] Univ Chile, Santiago, Chile. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 853 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202190 ER PT J AU Valent, D Wong, WT Chew, EY Cukras, CA AF Valent, David Wong, Wai T. Chew, Emily Y. Cukras, Catherine A. TI Oral Dextromethorphan for the Treatment of Diabetic Macular Edema: Results from a Phase I/II Clinical Study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Valent, David; Wong, Wai T.; Chew, Emily Y.; Cukras, Catherine A.] NEI, NIH, Washington, DC USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205282 ER PT J AU Wan, Q Hartford, J Memon, O Khristov, V Davis, J Miller, SS Bharti, K AF Wan, Qin Hartford, Juliet Memon, Omar Khristov, Vladimir Davis, Janine Miller, Sheldon S. Bharti, Kapil TI Primary Cilia Regulates the Polarization and Maturation of hiPSC-RPE through PKC-delta Activation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Wan, Qin; Memon, Omar; Miller, Sheldon S.] NEI, SERPD, NIH, Bethesda, MD 20892 USA. [Hartford, Juliet; Khristov, Vladimir; Davis, Janine; Bharti, Kapil] NEI, OSCTR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2345 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205346 ER PT J AU Weber, BHF Fleckenstein, M Chew, EY Schmitz-Valckenberg, S Goebel, AP Klein, ML Ratnapriya, R Swaroop, A Holz, FG Grassmann, F AF Weber, Bernhard H. F. Fleckenstein, Monika Chew, Emily Y. Schmitz-Valckenberg, Steffen Goebel, Arno P. Klein, Michael L. Ratnapriya, Rinki Swaroop, Anand Holz, Frank G. Grassmann, Felix TI Genetic and clinical factors associated with progression of geographic atrophy in age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Weber, Bernhard H. F.; Grassmann, Felix] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany. [Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Goebel, Arno P.; Holz, Frank G.] Univ Bonn, Dept Ophthalmol, D-53127 Bonn, Germany. [Chew, Emily Y.; Ratnapriya, Rinki; Swaroop, Anand] NEI, NIH, Bethesda, MD 20892 USA. [Klein, Michael L.] Oregon Hlth & Sci Univ, Casey Eye Inst, Macular Degenerat Ctr, Portland, OR 97201 USA. [Klein, Michael L.] Devers Eye Inst, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2828 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882206398 ER PT J AU Welsbie, DS Mitchell, KL Kim, J Martin, SE Fuller, JA Yang, ZY Ge, Y Buehler, E Berlinicke, C Zack, DJ AF Welsbie, Derek Stuart Mitchell, Katherine L. Kim, Jessica Martin, Scott E. Fuller, John A. Yang, Zhiyong Ge, Yan Buehler, Eugen Berlinicke, Cindy Zack, Donald J. TI A whole-genome, RNAi-based screen identifies activating transcription factor 2 (ATF2) genotropic activity as a key mediator of retinal ganglion cell death SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Welsbie, Derek Stuart; Mitchell, Katherine L.; Kim, Jessica; Fuller, John A.; Yang, Zhiyong; Ge, Yan; Berlinicke, Cindy; Zack, Donald J.] Johns Hopkins Univ, Sch Med, Ophthalmol, Baltimore, MD USA. [Martin, Scott E.; Buehler, Eugen] NIH, RNAi Screening Facil, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2593 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882206162 ER PT J AU Williams, EL Liu, BY Dhanda, A Lait, PJP Schewitz-Bowers, LP Collins, P Dick, AD Nussenblatt, RB Lee, RWJ AF Williams, Emily Louisa Liu, Baoying Dhanda, Ashwin Lait, Philippa J. P. Schewitz-Bowers, Lauren P. Collins, Peter Dick, Andrew D. Nussenblatt, Robert B. Lee, Richard W. J. TI Intermediate (CD14(++)CD16(+)) monocytes are expanded in non-infectious uveitis patients and have a reduced capacity to drive Th17 differentiation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Williams, Emily Louisa; Dhanda, Ashwin; Lait, Philippa J. P.; Schewitz-Bowers, Lauren P.; Dick, Andrew D.; Lee, Richard W. J.] Univ Bristol, Sch Clin Sci, Bristol, Avon, England. [Williams, Emily Louisa; Lait, Philippa J. P.; Schewitz-Bowers, Lauren P.; Dick, Andrew D.; Lee, Richard W. J.] Moorfields Eye Hosp, NIHR, Biomed Res Ctr, London, England. [Williams, Emily Louisa; Lait, Philippa J. P.; Schewitz-Bowers, Lauren P.; Dick, Andrew D.; Lee, Richard W. J.] UCL, Inst Ophthalmol, London, England. [Liu, Baoying; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Dhanda, Ashwin] Univ Plymouth, Peninsula Sch Med, Plymouth PL4 8AA, Devon, England. [Dhanda, Ashwin] Univ Plymouth, Peninsula Sch Dent, Plymouth PL4 8AA, Devon, England. [Collins, Peter] Univ Hosp Bristol NHS Fdn Trust, Bristol, Avon, England. [Nussenblatt, Robert B.] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 852 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202189 ER PT J AU Winokur, PN Subramanian, P Arocas, V Becerra, P AF Winokur, Paige Nicole Subramanian, Preeti Arocas, Veronique Becerra, Patricia TI Protease Nexin-1, a Novel Serpin in the Retinal Pigment Epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Winokur, Paige Nicole; Subramanian, Preeti; Becerra, Patricia] NEI, Sect Prot Struct & Funct, NIH, Bethesda, MD 20892 USA. [Arocas, Veronique] Hop Bichat Claude Bernard, Sect Claude Bernard, INSERM, 2U1148, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882205329 ER PT J AU Yamane, T Meguro, A Takeuchi, M Ideta, H Ideta, R Mizuki, N AF Yamane, Takahiro Meguro, Akira Takeuchi, Masaki Ideta, Hidenao Ideta, Ryuichi Mizuki, Nobuhisa TI Association study of RHBDD1-COL4A4 gene polymorphisms with susceptibility to lattice degeneration of the retina in a Japanese population SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Yamane, Takahiro; Meguro, Akira; Mizuki, Nobuhisa] Yokohama City Univ, Sch Med, Ophthalmol, Yokohama, Kanagawa 232, Japan. [Takeuchi, Masaki] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Ideta, Hidenao; Ideta, Ryuichi] Ideta Eye Hosp, Kumamoto, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1095 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882203004 ER PT J AU Yang, HJ Kim, JW Chaitankar, V Brooks, M Hao, H Swaroop, A AF Yang, Hyun-Jin Kim, Jung-Woong Chaitankar, Vijender Brooks, Matthew Hao, Hong Swaroop, Anand TI Integrated transcriptome and epigenome analysis of developing mouse rod photoreceptors reveals dynamic epigenetic control of lineage priming and developmental plasticity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Yang, Hyun-Jin; Kim, Jung-Woong; Chaitankar, Vijender; Brooks, Matthew; Hao, Hong; Swaroop, Anand] NEI, Neurodegenerat & Repair, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 437 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882201195 ER PT J AU Yiu, G Chiu, SJ Petrou, PA Stinnett, S Sarin, N Farsiu, S Chew, EY Wong, WT Toth, CA AF Yiu, Glenn Chiu, Stephanie J. Petrou, Philip A. Stinnett, Sandra Sarin, Neeru Farsiu, Sina Chew, Emily Y. Wong, Wai T. Toth, Cynthia A. TI Relationship of Central Choroidal Thickness with Age-Related Macular Degeneration Status SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Yiu, Glenn] Univ Calif Davis, Sacramento, CA USA. [Yiu, Glenn; Chiu, Stephanie J.; Stinnett, Sandra; Sarin, Neeru; Farsiu, Sina; Toth, Cynthia A.] Duke Univ, Med Ctr, Durham, NC USA. [Petrou, Philip A.; Chew, Emily Y.; Wong, Wai T.] NEI, Bethesda, MD 20892 USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2788 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882206358 ER PT J AU Yoshida, M Takeuchi, M Yamane, T Kawagoe, T Nakamura, J Sakono, T Okada, E AF Yoshida, Masao Takeuchi, Masaki Yamane, Takahiro Kawagoe, Tatsukata Nakamura, Jutaro Sakono, Takuji Okada, Eiichi TI A thirteen and a half year large scale follow-up study into the distribution of astigmatic axis in Japan. - The result of analysis of approximately 120,000 eyes of Japanese patients by spherical surface power and astigmatic power - SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Yoshida, Masao] Kyorin Univ, Sch Med, Dept Publ Hlth, Mitaka, Tokyo 181, Japan. [Takeuchi, Masaki] NHGRI, NIH, Bethesda, MD 20892 USA. [Yamane, Takahiro; Kawagoe, Tatsukata; Nakamura, Jutaro; Sakono, Takuji] Yokohama City Univ, Sch Med, Dept Ophthalmol, Yokohama, Kanagawa 232, Japan. [Okada, Eiichi] Okada Eye Clin, Yokohama, Kanagawa, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2942 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882207106 ER PT J AU Yu, CR Sun, L He, C Mahdi, RM Egwuagu, CE AF Yu, Chengrong Sun, Lin He, Chang Mahdi, Rashid M. Egwuagu, Chrales E. TI IL-21 induces Expansion of IL-35-producing B cells (i35-Bregs) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Yu, Chengrong; Sun, Lin; He, Chang; Mahdi, Rashid M.; Egwuagu, Chrales E.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 867 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882202204 ER PT J AU Zabel, M Zhao, L Wang, X Ma, WX Fariss, RN Qian, HH Parkhurst, C Gan, WB Wong, WT AF Zabel, Matthew Zhao, Lian Wang, Xu Ma, Wenxin Fariss, Robert N. Qian, Haohua Parkhurst, Christopher Gan, Wen-Biao Wong, Wai T. TI Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Zabel, Matthew; Zhao, Lian; Wang, Xu; Ma, Wenxin; Wong, Wai T.] NEI, UNGIRD, NIH, Bethesda, MD 20892 USA. [Fariss, Robert N.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA. [Qian, Haohua] NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA. [Parkhurst, Christopher; Gan, Wen-Biao] NYU, Sch Med, Dept Neurosci & Physiol, New York, NY USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 PG 3 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882206156 ER PT J AU Zelinger, L Kim, JW Yang, HJ Brooks, M Swaroop, A AF Zelinger, Lina Kim, Jung-Woong Yang, Hyun-Jin Brooks, Matthew Swaroop, Anand TI A possible role for lnc-RNA in mouse and human retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Zelinger, Lina; Kim, Jung-Woong; Yang, Hyun-Jin; Brooks, Matthew; Swaroop, Anand] NEI, N NRL, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 2602 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882206171 ER PT J AU Zhang, J Diamond, J AF Zhang, Jun Diamond, Jeffrey TI Synaptic localization of AMPAR subunits in A17 amacrine cells at the rod bipolar cell ribbon synapse SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 03-07, 2015 CL Denver, CO SP Assoc Res Vis & Ophthalmol C1 [Zhang, Jun; Diamond, Jeffrey] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 7 MA 1479 PG 2 WC Ophthalmology SC Ophthalmology GA CT5WQ UT WOS:000362882203369 ER PT J AU Hovey, RC Salomon, D AF Hovey, Russell C. Salomon, David TI The Journal of Mammary Gland Biology and Neoplasia into the Future - the Potential of Plasticity and Pluripotency SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Editorial Material C1 [Hovey, Russell C.] Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA. [Salomon, David] NCI, Ctr Canc Res, Frederick, MD 21702 USA. RP Hovey, RC (reprint author), Univ Calif Davis, Dept Anim Sci, 2145 Meyer Hall,One Shields Ave, Davis, CA 95616 USA. EM rchovey@ucdavis.edu NR 3 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 EI 1573-7039 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JUN PY 2015 VL 20 IS 1-2 SI SI BP 1 EP 3 DI 10.1007/s10911-015-9342-3 PG 3 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA CT0XA UT WOS:000362520000001 PM 26293595 ER PT J AU Boulanger, CA Rosenfield, SM George, AL Smith, GH AF Boulanger, Corinne A. Rosenfield, Sonia M. George, Andrea L. Smith, Gilbert H. TI Hormone Signaling Requirements for the Conversion of Non-Mammary Mouse Cells to Mammary Cell Fate(s) in Vivo SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Review DE Mammary; Niche; Estrogen; Amphiregulin; Progesterone; Prolactin; Hormone receptor ID ESTROGEN-RECEPTOR-ALPHA; GLAND DEVELOPMENT; PROGESTERONE-RECEPTOR; STEM-CELL; EPITHELIAL-CELLS; PROLACTIN GENE; MICE LACKING; STEROID-HORMONES; PROGENITOR CELLS; BREAST-CANCER AB Mammotropic hormones and growth factors play a very important role in mammary growth and differentiation. Here, hormones including Estrogen, Progesterone, Prolactin, their cognate receptors, and the growth factor Amphiregulin, are tested with respect to their roles in signaling non-mammary cells from the mouse to redirect to mammary epithelial cell fate(s). This was done in the context of glandular regeneration in pubertal athymic female mice. Our previous studies demonstrated that mammary stem cell niches are recapitulated during gland regeneration in vivo. During this process, cells of exogenous origin cooperate with mammary epithelial cells to form mammary stem cell niches and thus respond to normal developmental signals. In all cases tested with the possible exception of estrogen receptor alpha (ER-alpha), hormone signaling is dispensable for non-mammary cells to undertake mammary epithelial cell fate(s), proliferate, and contribute progeny to chimeric mammary outgrowths. Importantly, redirected non-mammary cell progeny, regardless of their source, have the ability to self-renew and contribute offspring to secondary mammary outgrowths derived from transplanted chimeric mammary fragments; thus suggesting that some of these cells are capable of mammary stem cell/progenitor functions. C1 [Boulanger, Corinne A.; Rosenfield, Sonia M.; George, Andrea L.; Smith, Gilbert H.] NCI, Mammary Stem Cell Biol Sect, BRL, CCR, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Mammary Stem Cell Biol Sect, BRL, CCR, Bldg 37,Rm 1122A, Bethesda, MD 20892 USA. EM gs4d@nih.gov NR 77 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 EI 1573-7039 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JUN PY 2015 VL 20 IS 1-2 SI SI BP 93 EP 101 DI 10.1007/s10911-015-9343-2 PG 9 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA CT0XA UT WOS:000362520000009 PM 26362796 ER PT J AU Rosen, J Miller, A Hughes, J Remington, J AF Rosen, Jonathan Miller, Aubrey Hughes, Joseph (Chip) Remington, James TI National Institute of Environmental Health Sciences Worker Training Program: Perspectives on the Health and Safety of Workers, Volunteers, and Residents Involved in the Cleanup and Rebuilding of New York City Housing Damaged by Hurricane Sandy SO ENVIRONMENTAL JUSTICE LA English DT Article AB Hurricane Sandy damaged or destroyed 76,000 buildings with over 300,000 housing units; nine percent of the total housing in New York City. Sandy also damaged 405 New York City Housing Authority (NYCHA) buildings, affecting 35,000 units. Affected residents were forced to move in with family, temporary housing, or endured long periods without heat or electricity, as most building systems were located in flooded basements. Additionally, workers, volunteers, and residents who engaged in cleanup were potentially exposed to raw sewage, mold, asbestos, lead, dust, carbon monoxide, as well as electrocution; slips, trips, and falls; and construction-related safety hazards. Stress and trauma were also significant. These exposures may cause death, disease, and injury. The need to provide protection programs and effective training crosses a number of populations including day laborers, volunteer groups, and residents who are involved in cleanup and rebuilding. The National Institute of Environmental Health Sciences (NIEHS) Worker Training Program (WTP) has provided funding to more than 20 grantees including universities, labor unions, and other organizations to provide effective worker health and safety and disaster preparedness and response training for more than 20 years. This has built a critical infrastructure in the targeted industrial sectors and unions. WTP has also been active in disasters including September 11, Katrina, the Gulf oil spill, and Sandy. Preventing injury and disease in all the groups that are involved in disaster response, cleanup, and rebuilding warrants extending the NIEHS health and safety programs to volunteers, residents, and worker populations who previously have not had access to hazardous materials and related training programs. This can be accomplished by adapting health and safety programs and just-in-time training to the needs and cultures of these groups. These efforts should also further ongoing approaches to empower grantees and end-users so that they can independently build dynamic health and safety and training programs into their disaster preparedness and response work. C1 [Rosen, Jonathan] Natl Clearinghouse Worker Safety & Hlth Training, Schenectady, NY 12303 USA. [Miller, Aubrey] NIEHS, Res Triangle Pk, NC 27709 USA. [Hughes, Joseph (Chip); Remington, James] NIEHS, Worker Training Program, Res Triangle Pk, NC 27709 USA. RP Rosen, J (reprint author), Natl Clearinghouse Worker Safety & Hlth Training, 110 Benjamin St, Schenectady, NY 12303 USA. EM jrosen396@gmail.com NR 0 TC 0 Z9 0 U1 3 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1939-4071 EI 1937-5174 J9 ENVIRON JUSTICE JI Environ. Justice PD JUN 1 PY 2015 VL 8 IS 3 BP 105 EP 109 DI 10.1089/env.2015.0008 PG 5 WC Environmental Studies SC Environmental Sciences & Ecology GA CS4WL UT WOS:000362076700006 ER PT J AU Kwako, LE Litten, RZ Momenan, R Koob, G Goldman, D AF Kwako, L. E. Litten, R. Z. Momenan, R. Koob, G. Goldman, D. TI ADDICTIONS NEUROCLINICAL ASSESSMENT: A NEW FRAMEWORK FOR UNDERSTANDING ALCOHOL USE DISORDER SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Kwako, L. E.; Litten, R. Z.; Momenan, R.; Koob, G.; Goldman, D.] NIAAA, NIH, Bethesda, MD 20892 USA. RI koob, george/P-8791-2016 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 026 BP 18A EP 18A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100027 ER PT J AU Corey, KM Stangl, BL Ramchandani, VA AF Corey, K. M. Stangl, B. L. Ramchandani, V. A. TI DETERMINANTS OF CONTROL OVER DRINKING AND IV ALCOHOL SELF-ADMINISTRATION IN NON-DEPENDENT DRINKERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Corey, K. M.; Stangl, B. L.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20814 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 098 BP 36A EP 36A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100099 ER PT J AU Mathur, K Momenan, R AF Mathur, K. Momenan, R. TI INVESTIGATING RISKY DECISION-MAKING AND TOLERANCE TO AMBIGUITY IN INDIVIDUALS WITH ALCOHOL USE DISORDERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Mathur, K.; Momenan, R.] NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 111 BP 39A EP 39A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100112 ER PT J AU Tapocik, JD Rauffenbart, C Pilling, A Solomon, M Heilig, M AF Tapocik, J. D. Rauffenbart, C. Pilling, A. Solomon, M. Heilig, M. TI DYSREGULATION OF MICRORNA-212 AND ITS TARGETED GENES IN THE RAT DORSAL STRIATUM FOLLOWING A HISTORY OF ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Tapocik, J. D.; Rauffenbart, C.; Pilling, A.; Solomon, M.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 149 BP 49A EP 49A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100150 ER PT J AU Abrahao, KP Lovinger, DM AF Abrahao, K. P. Lovinger, D. M. TI ELECTROPHYSIOLOGICAL CLASSIFICATION OF GLOBUS PALLIDUS NEURONS REVEALS THAT ETHANOL SPECIFICALLY DECREASES THE FIRING RATE OF LOW FREQUENCY NEURONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Abrahao, K. P.; Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20851 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 217 BP 66A EP 66A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100218 ER PT J AU Karlsson, C Rehman, F Damadzic, R Schank, JR Gehlert, DR Stensland, P Thorsell, A Heilig, M AF Karlsson, C. Rehman, F. Damadzic, R. Schank, J. R. Gehlert, D. R. Stensland, P. Thorsell, A. Heilig, M. TI THEMELANIN-CONCENTRATTING HORMONE-1 RECEPTOR (MCH-1R) MODULATES ALCOHOL-INDUCED REWARD AND P-DARPP-32 STIMULATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Karlsson, C.; Heilig, M.] Linkopings Univ, Linkoping, Sweden. [Rehman, F.; Damadzic, R.; Thorsell, A.; Heilig, M.] NIAAA, LCTS, NIH, Bethesda, MD USA. [Schank, J. R.] Univ Georgia, Athens, GA 30602 USA. [Gehlert, D. R.] Lilly Res Labs, Indianapolis, IN USA. [Stensland, P.] Karolinska Inst, Stockholm, Sweden. 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 224 BP 67A EP 67A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100225 ER PT J AU Augier, E Dulman, R Heilig, M AF Augier, E. Dulman, R. Heilig, M. TI CHOICE AS A SCREEN FOR COMPULSIVE ALCOHOL DRINKING IN RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Augier, E.; Dulman, R.; Heilig, M.] NIAAA, NIH, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 231 BP 69A EP 69A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100232 ER PT J AU Vatsalya, V Song, M Schwandt, M Mohammad, MK George, T Barve, S McClain, CJ AF Vatsalya, V. Song, M. Schwandt, M. Mohammad, M. K. George, T. Barve, S. McClain, C. J. TI ROLE OF DRINKING HISTORY AND SEX-DIFFERENCES IN METABOLITES INVOLVED IN INFLAMMATION IN ALCOHOL DEPENDENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Vatsalya, V.; Song, M.; Schwandt, M.; Mohammad, M. K.; George, T.; Barve, S.; McClain, C. J.] Univ Louisville, CTSI, Louisville, KY 40202 USA. [Vatsalya, V.; Song, M.; Schwandt, M.; Mohammad, M. K.; George, T.; Barve, S.; McClain, C. J.] NIAAA, NIH, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 254 BP 75A EP 75A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100255 ER PT J AU Farokhnia, M Edwards, S Zywiak, WH McGeary, JE Swift, RM Kenna, GA Leggio, L AF Farokhnia, M. Edwards, S. Zywiak, W. H. McGeary, J. E. Swift, R. M. Kenna, G. A. Leggio, L. TI EXPLORING THE BIOBEHAVIORAL MECHANISMS OF BACLOFEN IN ALCOHOLISM: A HUMAN LABORATORY STUDY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Farokhnia, M.; Edwards, S.; Zywiak, W. H.; McGeary, J. E.; Swift, R. M.; Kenna, G. A.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. RI Leggio, Lorenzo/M-2972-2016 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 267 BP 78A EP 78A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100268 ER PT J AU Le, AN Haass-Koffler, CL Zywiak, WH Brickley, M Edwards, SM Swift, RM Kenna, GA Leggio, L AF Le, A. N. Haass-Koffler, C. L. Zywiak, W. H. Brickley, M. Edwards, S. M. Swift, R. M. Kenna, G. A. Leggio, L. TI DOXAZOSIN FOR ALCOHOL DEPENDENCE: A PILOT DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Le, A. N.; Haass-Koffler, C. L.; Zywiak, W. H.; Brickley, M.; Edwards, S. M.; Swift, R. M.; Kenna, G. A.; Leggio, L.] NIAAA, CPN, Bethesda, MD 20814 USA. [Le, A. N.; Haass-Koffler, C. L.; Zywiak, W. H.; Brickley, M.; Edwards, S. M.; Swift, R. M.; Kenna, G. A.; Leggio, L.] NIDA, Bethesda, MD 20814 USA. [Le, A. N.; Haass-Koffler, C. L.; Zywiak, W. H.; Brickley, M.; Edwards, S. M.; Swift, R. M.; Kenna, G. A.; Leggio, L.] Brown Univ, Providence, RI 02903 USA. RI Leggio, Lorenzo/M-2972-2016 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 268 BP 78A EP 78A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100269 ER PT J AU Ryan, ML Devine, E Fertig, JB Falk, DE Litten, RZ AF Ryan, M. L. Devine, E. Fertig, J. B. Falk, D. E. Litten, R. Z. TI A COMPUTERIZED BEHAVIORAL PLATFORM FOR PHARMACOTHERAPY CLINICAL TRIALS FOR ALCOHOL USE DISORDERS: TAKE CONTROL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Ryan, M. L.; Fertig, J. B.; Falk, D. E.; Litten, R. Z.] NIAAA, NIH, Bethesda, MD 20892 USA. [Devine, E.] Boston Univ, Sch Med, Boston, MA 02118 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 270 BP 79A EP 79A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100271 ER PT J AU Fertig, JB Ryan, ML Falk, DE Litten, RZ AF Fertig, J. B. Ryan, M. L. Falk, D. E. Litten, R. Z. TI MODERATORS OF THE VARENICLINE TREATMENT EFFECT IN A DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL FOR ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Fertig, J. B.; Ryan, M. L.; Falk, D. E.; Litten, R. Z.] NIAAA, Bethesda, MD 20982 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 274 BP 80A EP 80A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100275 ER PT J AU Brennan, GM Momenan, R AF Brennan, G. M. Momenan, R. TI CHARACTERIZING ALCOHOL-DEPENDENT AND NON-DEPENDENT HEAVY-DRINKING POPULATIONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Brennan, G. M.; Momenan, R.] NIAAA, Lab Clin & Translat Studies, Sect Brain Electrophysiol & Imaging, Bethesda, MD 20895 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 301 BP 87A EP 87A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100302 ER PT J AU Blau, LE Stangl, BL Ramchandani, VA AF Blau, L. E. Stangl, B. L. Ramchandani, V. A. TI CHARACTERIZATION OF HANGOVER SYMPTOMS AFTER IV ALCOHOL SELF-ADMINISTRATION IN NON-DEPENDENT DRINKERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Blau, L. E.; Stangl, B. L.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 332 BP 94A EP 94A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100333 ER PT J AU Momenan, R Cortes, C Mann, C Mathur, K DiazGranados, N George, D Heilig, M AF Momenan, R. Cortes, C. Mann, C. Mathur, K. DiazGranados, N. George, D. Heilig, M. TI A LOOK INSIDE ALCOHOL-DEPENDENT SUBJECTS BEHAVIOR AND NEUROFUNCTION IN SOCIAL INTERACTIONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Momenan, R.; Cortes, C.; Mann, C.; Mathur, K.; DiazGranados, N.; George, D.; Heilig, M.] NIAAA, NIH, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 376 BP 105A EP 105A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100377 ER PT J AU Jury, NJ Bergstrom, HC Pinard, CR Holmes, A AF Jury, N. J. Bergstrom, H. C. Pinard, C. R. Holmes, A. TI NEURAL AND BEHAVIORAL EFFECTS OF CHRONIC INTERMITTENT ETHANOL VAPOR EXPOSURE IN ADOLESCENT AND FEMALE MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Jury, N. J.; Bergstrom, H. C.; Pinard, C. R.; Holmes, A.] NIAAA, Lab Behav & Genom Neurosci, NIH, Rockville, MD 20852 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 388 BP 108A EP 108A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100388 ER PT J AU Nelson, BS King, CE Heilig, M Schank, JR AF Nelson, B. S. King, C. E. Heilig, M. Schank, J. R. TI REINSTATEMENT OF ALCOHOL SEEKING INDUCED BY FOOTSHOCK OR ALCOHOL PRIMING DIFFERS BETWEEN WISTAR AND ALCOHOL PREFERRING (P) RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Nelson, B. S.; Schank, J. R.] Univ Georgia, Dept Physiol & Pharmacol, Athens, GA 30602 USA. [King, C. E.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 396 BP 110A EP 110A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637100396 ER PT J AU Enoch, MA Kitzman, H Smith, JA Anson, E Hodgkinson, CA Goldman, D Olds, D AF Enoch, M. -A. Kitzman, H. Smith, J. A. Anson, E. Hodgkinson, C. A. Goldman, D. Olds, D. TI A PROSPECTIVE COHORT STUDY OF INFLUENCES ON INTERNALIZING AND EXTERNALIZING BEHAVIORS ACROSS CHILDHOOD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Enoch, M. -A.; Kitzman, H.; Smith, J. A.; Anson, E.; Hodgkinson, C. A.; Goldman, D.; Olds, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Enoch, M. -A.; Kitzman, H.; Smith, J. A.; Anson, E.; Hodgkinson, C. A.; Goldman, D.; Olds, D.] Univ Rochester, Sch Nursing, Rochester, NY 14642 USA. [Enoch, M. -A.; Kitzman, H.; Smith, J. A.; Anson, E.; Hodgkinson, C. A.; Goldman, D.; Olds, D.] Univ Colorado, Dept Pediat, Aurora, CO 80045 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 483 BP 132A EP 132A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101006 ER PT J AU Durrani, AM O'Connor, S Plawecki, MH Ramchandani, VA AF Durrani, A. M. O'Connor, S. Plawecki, M. H. Ramchandani, V. A. TI BIOAVAILABILITY OF ALCOHOL FOLLOWING ORAL INGESTION IN HUMANS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Durrani, A. M.; O'Connor, S.; Plawecki, M. H.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, LCTS, Bethesda, MD USA. [Durrani, A. M.; O'Connor, S.; Plawecki, M. H.; Ramchandani, V. A.] Indiana Univ Sch Med, Indianapolis, IN 46202 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 493 BP 134A EP 134A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101016 ER PT J AU Vatsalya, V Schmidt, V Ramchandani, V AF Vatsalya, V. Schmidt, V. Ramchandani, V. TI ROLE OF FAMILY HISTORYOF ALCOHOLISM AND RECENT DRINKING ON SUBJECTIVE & OBJECTIVE RESPONSES TO ACUTE IV ALCOHOL: CLAMP AND BIPHASIC EXPOSURE PROFILES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Vatsalya, V.; Schmidt, V.; Ramchandani, V.] NIAAA, Sect Human Psychopharmacol, LCTS, NIH, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 496 BP 135A EP 135A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101019 ER PT J AU Westman, JG Gowin, JL Vatsalya, V Schwandt, ML Momenan, R Bartlett, SE Heilig, M Ramchandani, VA AF Westman, J. G. Gowin, J. L. Vatsalya, V. Schwandt, M. L. Momenan, R. Bartlett, S. E. Heilig, M. Ramchandani, V. A. TI VARENICLINE DIMINISHES AMYGDALAR BOLD RESPONSE TO NEGATIVE FACIAL EXPRESSION CUES IN HEAVY DRINKERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Westman, J. G.; Gowin, J. L.; Vatsalya, V.; Schwandt, M. L.; Momenan, R.; Bartlett, S. E.; Heilig, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, LCTS, NIH, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 551 BP 149A EP 149A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101074 ER PT J AU Cortes, CR Zhu, X Mathur, K Grodin, EN Sarlls, J Diazgranados, N George, D Momenan, R AF Cortes, C. R. Zhu, X. Mathur, K. Grodin, E. N. Sarlls, J. Diazgranados, N. George, D. Momenan, R. TI FUNCTIONAL CONNECTIVITY AND WHITE MATER INTEGRITY UNDERLYING ALCOHOL CONSUMPTION AND IMPULSIVITY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Cortes, C. R.; Zhu, X.; Mathur, K.; Grodin, E. N.; Sarlls, J.; Diazgranados, N.; George, D.; Momenan, R.] NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 554 BP 150A EP 150A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101077 ER PT J AU Zhu, X Sundby, K Momenan, R Bjork, J AF Zhu, X. Sundby, K. Momenan, R. Bjork, J. TI FUNCTIONAL BRAIN NETWORKS ASSOCIATED WITH DECISION-MAKING AND RISKY BEHAVIOR IN SUBSTANCE DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 NIAAA, Sect Brain Electrophysiol & Imaging, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 561 BP 151A EP 151A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101084 ER PT J AU Brietzke, S Cortes, CR Momenan, R AF Brietzke, S. Cortes, C. R. Momenan, R. TI STRIATAL ACTIVATION FOR NON-DRUG REWARD AND LOSS CUES IN ALCOHOLIC DEPENDENTS: A FMRI STUDY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Brietzke, S.; Cortes, C. R.; Momenan, R.] NIAAA, Sect Brain Electrophysiol & Imaging, Lab Clin & Translat Studies, NIH, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 563 BP 152A EP 152A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101086 ER PT J AU Grodin, EN Steckler, LE Momenan, R AF Grodin, E. N. Steckler, L. E. Momenan, R. TI MODULATION OF BRAIN RESPONSE DURING EFFORT-BASED DECISION-MAKING IN ALCOHOL-DEPENDENT PATIENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Grodin, E. N.; Steckler, L. E.; Momenan, R.] NIAAA, Sect Brain Electrophysiol & Imaging, Lab Clin & Translat Sci, NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 562 BP 152A EP 152A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101085 ER PT J AU Schwandt, ML Heilig, M George, DT Hommer, DW Ramchandani, VA AF Schwandt, M. L. Heilig, M. George, D. T. Hommer, D. W. Ramchandani, V. A. TI CHILDHOOD TRAUMA IN ALCOHOL DEPENDENCE: CHARACTERIZING RESILIENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Schwandt, M. L.; Heilig, M.; George, D. T.; Hommer, D. W.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 577 BP 155A EP 155A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101100 ER PT J AU Liu, H Ramsden, C Feldstein, A McClain, C Kirpich, I AF Liu, H. Ramsden, C. Feldstein, A. McClain, C. Kirpich, I. TI 12/15-LIPOXYGENASE INHIBITION AMELIORATES ALCOHOL-INDUCED LIVER INJURY AND INFLAMMATION IN A MOUSE MODEL OF ALCOHOLIC LIVER DISEASE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 Univ Louisville, Sch Med, Louisville, KY 40292 USA. NIAAA, Bethesda, MD USA. Univ Calif San Diego, San Diego, CA 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 637 BP 170A EP 170A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101160 ER PT J AU Zhu, X Momenan, R Lohoff, F AF Zhu, X. Momenan, R. Lohoff, F. TI GENETIC VARIATION IN VESICULAR MONOAMINE TRANSPORTER 1 MODULATE SPONTANEOUS BRAIN FUNCTIONAL CONNECTIVITY IN ALCOHOLICS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Zhu, X.; Momenan, R.; Lohoff, F.] NIAAA, LCTS, NIH, Bethesda, MD 20892 USA. RI Lohoff, Falk/M-7951-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 666 BP 177A EP 177A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101188 ER PT J AU Saitz, R Heeren, TC Zha, W Hingson, RW AF Saitz, R. Heeren, T. C. Zha, W. Hingson, R. W. TI TRANSITIONS TO AND FROM AT-RISK ALCOHOL USE IN ADULTS IN THE UNITED STATES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NIAAA, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 741 BP 196A EP 196A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101263 ER PT J AU Yan, J Schwandt, ML Aggen, SH George, DT Heilig, M Kendler, KS Ramchandani, VA AF Yan, J. Schwandt, M. L. Aggen, S. H. George, D. T. Heilig, M. Kendler, K. S. Ramchandani, V. A. TI DSM-IV CRITERIA FOR ALCOHOL ABUSE AND DEPENDENCE IN A TREATMENT-SEEKING SAMPLE: NUMBER OF DIMENSIONS AND VALIDATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 NIAAA, LCTS, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 752 BP 198A EP 198A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101274 ER PT J AU Hingson, R Zha, W Simons-Morton, B Li, K AF Hingson, R. Zha, W. Simons-Morton, B. Li, K. TI ARE ADOLESCENTS WHO DRIVE AFTER DRINKING, MARIJUANA USE, AND OTHER DRUG USE MORE LIKELY TO ENGAGE IN OTHER RISKY BEHAVIORS IN TRAFFIC? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Hingson, R.; Zha, W.] NIAAA, Bethesda, MD 20892 USA. [Simons-Morton, B.; Li, K.] NICHHD, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 757 BP 200A EP 200A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101279 ER PT J AU Vatsalya, V Beri, A Ramchandani, VA McClain, CJ Barve, S AF Vatsalya, V. Beri, A. Ramchandani, V. A. McClain, C. J. Barve, S. TI ASSOCIATION OF LIVER INJURY EXACERBATION AND FATTY ACIDS OFW-6 ANDW-3 INFLAMMATORY PATHWAYS IN EARLY-STAGE HIV-DIAGNOSED ALCOHOLIC PATIENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Vatsalya, V.; Beri, A.; Ramchandani, V. A.; McClain, C. J.; Barve, S.] Univ Louisville, CTSI, Louisville, KY 40202 USA. [Vatsalya, V.; Beri, A.; Ramchandani, V. A.; McClain, C. J.; Barve, S.] NIAAA, Bethesda, MD 20892 USA. [Vatsalya, V.; Beri, A.; Ramchandani, V. A.; McClain, C. J.; Barve, S.] NIH, Ctr Clin, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 875 BP 229A EP 229A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101397 ER PT J AU Haass-Koffler, CL Aoun, EG Kenna, GA de la Monte, SM Swift, RM Leggio, L AF Haass-Koffler, C. L. Aoun, E. G. Kenna, G. A. de la Monte, S. M. Swift, R. M. Leggio, L. TI EXOGENOUS INTRAVENOUS GHRELIN ADMINISTRATION DECREASES ENDOGENOUS SERUM LEPTIN LEVEL AND INCREASES ALCOHOL CRAVING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Haass-Koffler, C. L.; Aoun, E. G.; Kenna, G. A.; de la Monte, S. M.; Swift, R. M.; Leggio, L.] NIAAA, CPN, Bethesda, MD 20814 USA. [Haass-Koffler, C. L.; Aoun, E. G.; Kenna, G. A.; de la Monte, S. M.; Swift, R. M.; Leggio, L.] NIDA, Bethesda, MD 20814 USA. [Haass-Koffler, C. L.; Aoun, E. G.; Kenna, G. A.; de la Monte, S. M.; Swift, R. M.; Leggio, L.] Brown Univ, Providence, RI 02903 USA. RI Leggio, Lorenzo/M-2972-2016 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 892 BP 233A EP 233A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101414 ER PT J AU Gowin, JL Vatsalya, V Momenan, R Schwandt, ML Bartlett, S Heilig, M Ramchandani, VA AF Gowin, J. L. Vatsalya, V. Momenan, R. Schwandt, M. L. Bartlett, S. Heilig, M. Ramchandani, V. A. TI ATTENUATION OF DEFAULT MODE NETWORK ACTIVITY DURING A TASK BY VARENICLINE IN HEAVY DRINKERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Gowin, J. L.; Vatsalya, V.; Momenan, R.; Schwandt, M. L.; Bartlett, S.; Heilig, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 902 BP 236A EP 236A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101424 ER PT J AU Barbier, E Tapocik, J Johnstone, A Zhou, Z Yuan, Q Goldman, D Wahlestedt, C Heilig, M AF Barbier, E. Tapocik, J. Johnstone, A. Zhou, Z. Yuan, Q. Goldman, D. Wahlestedt, C. Heilig, M. TI THE METHYLTRANSFERASE PRDM2 REGULATES ESCALATED ALCOHOL CONSUMPTION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Barbier, E.; Tapocik, J.; Johnstone, A.; Zhou, Z.; Yuan, Q.; Goldman, D.; Wahlestedt, C.; Heilig, M.] Linkoping Univ, Linkoping, Sweden. [Barbier, E.; Tapocik, J.; Johnstone, A.; Zhou, Z.; Yuan, Q.; Goldman, D.; Wahlestedt, C.; Heilig, M.] NIAAA, LCTS, Bethesda, MD USA. [Barbier, E.; Tapocik, J.; Johnstone, A.; Zhou, Z.; Yuan, Q.; Goldman, D.; Wahlestedt, C.; Heilig, M.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 918 BP 240A EP 240A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101440 ER PT J AU Dutta, N Helton, SG Hall, S Schwandt, M Lohoff, FW AF Dutta, N. Helton, S. G. Hall, S. Schwandt, M. Lohoff, F. W. TI ALCOHOL WITHDRAWAL SEVERITY IS MODERATED BY THE VMAT1 FUNCTIONAL VARIANT THR136ILE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Dutta, N.; Helton, S. G.; Hall, S.; Schwandt, M.; Lohoff, F. W.] NIAAA, Lab Clin Genom & Expt Therapeut, NIH, Bethesda, MD 20892 USA. RI Lohoff, Falk/M-7951-2016 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 943 BP 246A EP 246A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101465 ER PT J AU Helton, SG Dutta, N Hall, S Schwandt, M Lohoff, FW AF Helton, S. G. Dutta, N. Hall, S. Schwandt, M. Lohoff, F. W. TI ASSOCIATION ANALYSIS BETWEEN VARIANTS IN THE GENOME-WIDE SUPPORTED GATA4 CANDIDATE GENE AND ALCOHOLISM: A REPLICATION STUDY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Helton, S. G.; Dutta, N.; Hall, S.; Schwandt, M.; Lohoff, F. W.] NIAAA, Lab Clin Genom & Expt Therapeut, NIH, Bethesda, MD 20892 USA. RI Lohoff, Falk/M-7951-2016 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 945 BP 247A EP 247A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101467 ER PT J AU Spagnolo, PA Schawndt, ML Yan, J Kwako, LE George, DT Ramchandani, V Heilig, M AF Spagnolo, P. A. Schawndt, M. L. Yan, J. Kwako, L. E. George, D. T. Ramchandani, V. Heilig, M. TI EFFECTS OF FAAH AND CRHR1 RS110402 POLYMORPHISMS ON SUBJECTIVE AND NEUROENDOCRINE RESPONSE TO STRESS IN ALCOHOL-DEPENDENT SUBJECTS WITH PTSD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Spagnolo, P. A.; Schawndt, M. L.; Yan, J.; Kwako, L. E.; George, D. T.; Ramchandani, V.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 949 BP 248A EP 248A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101471 ER PT J AU Stangl, BL Westman, JG Corey, K Blau, L Kwako, LE Sinha, R Ramchandani, VA AF Stangl, B. L. Westman, J. G. Corey, K. Blau, L. Kwako, L. E. Sinha, R. Ramchandani, V. A. TI A HUMAN EXPERIMENTAL MODEL OF STRESS-INDUCED ALCOHOL SELF-ADMINISTRATION: INFLUENCE OF BINGE DRINKING HISTORY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Stangl, B. L.; Westman, J. G.; Corey, K.; Blau, L.; Kwako, L. E.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20814 USA. [Sinha, R.] Yale Univ, Sch Med, Yale Stress Ctr, New Haven, CT 06519 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 037 BP 259A EP 259A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101515 ER PT J AU Brooks, AT Krumlauf, M Schwandt, ML Ramchandani, VA Wallen, GR AF Brooks, A. T. Krumlauf, M. Schwandt, M. L. Ramchandani, V. A. Wallen, G. R. TI SLEEP DISTURBANCE IN INDIVIDUALS WITH ALCOHOL DEPENDENCE: FINDINGS FROM AN EXPLORATORY MIXED METHODS STUDY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Brooks, A. T.; Krumlauf, M.; Schwandt, M. L.; Ramchandani, V. A.; Wallen, G. R.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 092 BP 272A EP 272A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101570 ER PT J AU Pava, MJ Lovinger, DM AF Pava, M. J. Lovinger, D. M. TI SLEEP DISRUPTIONS IN A MURINE MODEL OF ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Pava, M. J.; Lovinger, D. M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, DICBR,NIH, Gaithersburg, 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 089 BP 272A EP 272A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101567 ER PT J AU Enoch, MA Harris, CR Ducci, F Albaugh, B Goldman, D AF Enoch, M. -A. Harris, C. R. Ducci, F. Albaugh, B. Goldman, D. TI GENETIC, ENVIRONMENTAL AND G X E INTERACTIVE EFFECTS ON ALCOHOL USE DISORDERS IN AMERICAN INDIANS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Enoch, M. -A.; Harris, C. R.; Ducci, F.; Albaugh, B.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 093 BP 273A EP 273A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637101571 ER PT J AU Seif, T Simms, JA Bonci, A Messing, RO Hopf, FW AF Seif, T. Simms, J. A. Bonci, A. Messing, R. O. Hopf, F. W. TI INSULA, NUCLEUS ACCUMBENS, AND NMDA RECEPTOR REGULATION OF COMPULSION-LIKE, AVERSION-RESISTANT ALCOHOL DRINKING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Seif, T.; Simms, J. A.; Bonci, A.; Messing, R. O.; Hopf, F. W.] Univ Calif San Francisco, Deparment Neurol, Sf, CA USA. [Seif, T.; Simms, J. A.; Bonci, A.; Messing, R. O.; Hopf, F. W.] NIDA, Intramural Res Program, Baltimore, MD USA. [Seif, T.; Simms, J. A.; Bonci, A.; Messing, R. O.; Hopf, F. W.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 134 BP 283A EP 283A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637102018 ER PT J AU Bertola, A Xu, MJ Cai, Y Deng, C Gao, B AF Bertola, A. Xu, M. J. Cai, Y. Deng, C. Gao, B. TI HEPATOCYTE AND MYELOID SIRT6 CONTRIBUTE TO CHRONIC PLUS BINGE ETHANOL FEEDING-INDUCED LIVER INJURY IN MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Bertola, A.; Xu, M. J.; Cai, Y.; Deng, C.; Gao, B.] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 163 BP 290A EP 290A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637102047 ER PT J AU Li, X AF Li, X. TI ROLE OF HEPATIC AND INTESTINAL SIRT1 IN NAFLD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Li, X.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 161 BP 290A EP 290A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637102045 ER PT J AU Ramirez, T Li, Y Feng, D Ding, WX Gao, B AF Ramirez, T. Li, Y. Feng, D. Ding, W. X. Gao, B. TI AGING DOWNREGULATES HEPATIC SIRTUIN 1 AND EXACERBATES CHRONIC-PLUS-BINGE ETHANOL-INDUCED LIVER INJURY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Ramirez, T.; Li, Y.; Feng, D.; Ding, W. X.; Gao, B.] NIH, NIAAA, Bethesda, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 162 BP 290A EP 290A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637102046 ER PT J AU Hagman, BT Martin, CS AF Hagman, B. T. Martin, C. S. TI TOWARD EFFICIENT SCREENING FOR DSM-5 AUD IN ADOLESCENTS AND YOUNG ADULTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 [Hagman, B. T.; Martin, C. S.] NIAAA, Div Treatment & Recovery Res, Rockville, MD 20892 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 214 BP 303A EP 303A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637102098 ER PT J AU Lee, MR Tanda, G Rohn, M Yan, J Ramchandani, VA Schwandt, ML Newman, AH Leggio, L AF Lee, M. R. Tanda, G. Rohn, M. Yan, J. Ramchandani, V. A. Schwandt, M. L. Newman, A. H. Leggio, L. TI IMPORTANCE OF OXYTOCIN AND DOPAMINE IN ADDICTION: A TRANSLATIONAL APPROACH SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 38th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 20-24, 2015 CL San Antonio, TX SP Res Soc Alcoholism C1 NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, NIH, Bethesda, MD USA. NIDA, NIH, Bethesda, MD 20892 USA. RI Tanda, Gianluigi/B-3318-2009; Leggio, Lorenzo/M-2972-2016 OI Tanda, Gianluigi/0000-0001-9526-9878; 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 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2015 VL 39 SU 1 SI SI MA 228 BP 306A EP 306A PG 1 WC Substance Abuse SC Substance Abuse GA CR8XG UT WOS:000361637102112 ER PT J AU Thordardottir, M Lindqvist, E Lund, SH Costello, R Burton, D Korde, N Mailankody, S Eiriksdottir, G Launer, LJ Gudnason, V Harris, TB Landgren, O Kristinsson, SY AF Thordardottir, M. Lindqvist, E. Lund, S. H. Costello, R. Burton, D. Korde, N. Mailankody, S. Eiriksdottir, G. Launer, L. J. Gudnason, V. Harris, T. B. Landgren, O. Kristinsson, S. Y. TI OBESITY AND RISK OF MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE: A POPULATION-BASED STUDY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 20th Congress of European-Hematology-Association CY JUN 11-14, 2015 CL Vienna, AUSTRIA C1 [Thordardottir, M.; Lund, S. H.; Gudnason, V.; Kristinsson, S. Y.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Lindqvist, E.; Landgren, O.; Kristinsson, S. Y.] Karolinska Univ Hosp, Div Hematol, Dept Med, Stockholm, Sweden. [Lindqvist, E.; Landgren, O.; Kristinsson, S. Y.] Karolinska Inst, Stockholm, Sweden. [Costello, R.; Burton, D.; Mailankody, S.] NCI, Multiple Myeloma Sect, NIH, Bethesda, MD 20892 USA. [Korde, N.; Landgren, O.] Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, Myeloma Serv, New York, NY 10021 USA. [Eiriksdottir, G.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Launer, L. J.; Harris, T. B.] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2015 VL 100 SU 1 MA P281 BP 87 EP 87 PG 1 WC Hematology SC Hematology GA CR3BJ UT WOS:000361204901183 ER PT J AU Aradttir, K Lund, SH Bjorkholm, M Goldin, LR Turesson, I Landgren, O Kristinsson, SY AF Aradttir, K. Lund, S. H. Bjorkholm, M. Goldin, L. R. Turesson, I. Landgren, O. Kristinsson, S. Y. TI FAMILY HISTORY OF LYMPHOPROLIFERATIVE DISEASE ASSOCIATED WITH A SUPERIOR SURVIVAL IN MULTIPLE MYELOMA: A POPULATION-BASED STUDY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 20th Congress of European-Hematology-Association CY JUN 11-14, 2015 CL Vienna, AUSTRIA C1 [Aradttir, K.; Lund, S. H.; Kristinsson, S. Y.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Bjorkholm, M.; Kristinsson, S. Y.] Karolinska Univ Hosp, Dept Med, Stockholm, Sweden. [Bjorkholm, M.; Kristinsson, S. Y.] Karolinska Inst, Stockholm, Sweden. [Goldin, L. R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Turesson, I.] Skane Univ Hosp, Dept Hematol & Coagulat Disorders, Malmo, Sweden. [Landgren, O.] Mem Sloan Kettering Canc Ctr, Myeloma Serv, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2015 VL 100 SU 1 MA P292 BP 92 EP 93 PG 2 WC Hematology SC Hematology GA CR3BJ UT WOS:000361204901194 ER PT J AU Sverrisdottir, IS Lund, SH Turesson, I Bojrkholm, M Goldin, LR Landgren, O Kristinsson, SY AF Sverrisdottir, I. S. Lund, S. H. Turesson, I. Bojrkholm, M. Goldin, L. R. Landgren, O. Kristinsson, S. Y. TI PARENTAL LONGEVITY AND SURVIVAL IN PATIENTS WITH MULTIPLE MYELOMA AND MGUS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 20th Congress of European-Hematology-Association CY JUN 11-14, 2015 CL Vienna, AUSTRIA C1 [Sverrisdottir, I. S.] Univ Iceland, Natl Univ Hosp, Landspitali, Reykjavik, Iceland. [Lund, S. H.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Turesson, I.] Skane Univ Hosp, Malmo, Sweden. [Bojrkholm, M.] Karolinska Univ Hosp, Div Hematol, Dept Med, Stockholm, Sweden. [Bojrkholm, M.] Karolinska Inst, Stockholm, Sweden. [Goldin, L. R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Landgren, O.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Hematol Oncol, Myeloma Serv, New York, NY 10021 USA. [Kristinsson, S. Y.] Natl Univ Hosp Reykjavik, Dept Hematol, Landspitali, Reykjavik, Iceland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2015 VL 100 SU 1 MA P293 BP 93 EP 93 PG 1 WC Hematology SC Hematology GA CR3BJ UT WOS:000361204901195 ER PT J AU Psaila, B Iskander, D Mead, A Roy, A Milojkovic, D Chaidos, A Loaiza, S Caputo, V Ashley, N Karadimitris, A Roberts, I AF Psaila, B. Iskander, D. Mead, A. Roy, A. Milojkovic, D. Chaidos, A. Loaiza, S. Caputo, V. Ashley, N. Karadimitris, A. Roberts, I. TI PROSPECTIVE ISOLATION OF NOVEL POPULATIONS OF MEGAKARYOCYTE-AND ERYTHROID-PRIMED MEGAKARYOCYTE-ERYTHROID PROGENITORS DEMONSTRATES MEGAKARYOCYTE-BIASED LINEAGE COMMITMENT IN PRIMARY MYELOFIBROSIS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 20th Congress of European-Hematology-Association CY JUN 11-14, 2015 CL Vienna, AUSTRIA C1 [Psaila, B.; Iskander, D.; Roy, A.; Milojkovic, D.; Chaidos, A.; Loaiza, S.; Caputo, V.; Karadimitris, A.; Roberts, I.] Univ London Imperial Coll Sci Technol & Med, Haematol, London, England. [Psaila, B.] NHGRI, Hematopoiesis, NIH, Bethesda, MD 20892 USA. [Mead, A.; Ashley, N.; Roberts, I.] Weatherall Inst Mol Med, MRC, Mol Haematol Unit, Oxford, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2015 VL 100 SU 1 MA P300 BP 97 EP 97 PG 1 WC Hematology SC Hematology GA CR3BJ UT WOS:000361204901204 ER PT J AU Minniti, C Bonham, V Findley, K Abdallah, K Buscetta, A AF Minniti, C. Bonham, V. Findley, K. Abdallah, K. Buscetta, A. TI PHENOTYPIC VARIATIONS IN SICKLE CELL DISEASE: AN EXPLORATION OF THE ROLE OF THE ENVIRONMENT AND SKIN MICROBIOME ON LEG ULCERS SO HAEMATOLOGICA LA English DT Meeting Abstract CT 20th Congress of European-Hematology-Association CY JUN 11-14, 2015 CL Vienna, AUSTRIA C1 [Minniti, C.] Albert Einstein Coll Med, Hematol, Bronx, NY 10467 USA. [Bonham, V.; Findley, K.; Abdallah, K.; Buscetta, A.] NHGRI, NIH, Bethesda, MD 20892 USA. EM bonhamv@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2015 VL 100 SU 1 MA P735 BP 291 EP 291 PG 1 WC Hematology SC Hematology GA CR3BJ UT WOS:000361204902239 ER PT J AU Jones, JA Andritsos, L Ravandi, F Kreitman, RJ Schiffer, C Call, T Lozanski, G Sexton, J Harris, P Grever, MR AF Jones, J. A. Andritsos, L. Ravandi, F. Kreitman, R. J. Schiffer, C. Call, T. Lozanski, G. Sexton, J. Harris, P. Grever, M. R. TI SAFETY AND EFFICACY OF THE BRUTON TYROSINE KINASE INHIBITOR IBRUTINIB IN PATIENTS WITH HAIRY CELL LEUKEMIA: INTERIM RESULTS OF A PHASE 2 STUDY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 20th Congress of European-Hematology-Association CY JUN 11-14, 2015 CL Vienna, AUSTRIA C1 [Jones, J. A.; Andritsos, L.; Grever, M. R.] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA. [Ravandi, F.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Kreitman, R. J.] NCI, Clin Immunotherapy Sect, Bethesda, MD 20892 USA. [Schiffer, C.] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Call, T.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Lozanski, G.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Sexton, J.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Harris, P.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2015 VL 100 SU 1 MA S790 BP 313 EP 313 PG 1 WC Hematology SC Hematology GA CR3BJ UT WOS:000361204902294 ER PT J AU Bodine, D O'Brien, K Vlachos, A Farrar, J Blanc, L Anderson, S Ellis, S Lipton, J AF Bodine, D. O'Brien, K. Vlachos, A. Farrar, J. Blanc, L. Anderson, S. Ellis, S. Lipton, J. CA NI Sequencing Ctr TI CELLULAR AND MOLECULAR CHARACTERIZATION OF ERYTHROID DEFECTS IN DIAMOND BLACKFAN ANEMIA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 20th Congress of European-Hematology-Association CY JUN 11-14, 2015 CL Vienna, AUSTRIA C1 [Bodine, D.; O'Brien, K.; Anderson, S.; NI Sequencing Ctr] NHGRI, NIH, Bethesda, MD 20892 USA. [Vlachos, A.; Blanc, L.; Lipton, J.] Feinstein Inst, New Hyde Pk, NY USA. [Farrar, J.] Univ Arkansas, Little Rock, AR 72204 USA. [Ellis, S.] Univ Louisville, Louisville, KY 40292 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2015 VL 100 SU 1 MA S825 BP 331 EP 331 PG 1 WC Hematology SC Hematology GA CR3BJ UT WOS:000361204902329 ER PT J AU Townsley, D Dumitriu, B Phillip, S Desmond, R Feng, X Rios, O Weinstein, B Valdez, J Winkler, T Keyvanfar, K Sellers, S Desierto, M Soltani, S Leuva, H Valluri, S Wu, C Calvo, K Larochelle, A Dunbar, C Young, N AF Townsley, D. Dumitriu, B. Phillip, S. Desmond, R. Feng, X. Rios, O. Weinstein, B. Valdez, J. Winkler, T. Keyvanfar, K. Sellers, S. Desierto, M. Soltani, S. Leuva, H. Valluri, S. Wu, C. Calvo, K. Larochelle, A. Dunbar, C. Young, N. TI ELTROMBOPAG ADDED TO STANDARD IMMUNOSUPPRESSION AS FIRST TREATMENT IN SEVERE APLASTIC ANEMIA SO HAEMATOLOGICA LA English DT Meeting Abstract CT 20th Congress of European-Hematology-Association CY JUN 11-14, 2015 CL Vienna, AUSTRIA C1 [Townsley, D.; Dumitriu, B.; Feng, X.; Rios, O.; Weinstein, B.; Valdez, J.; Winkler, T.; Keyvanfar, K.; Sellers, S.; Desierto, M.; Soltani, S.; Leuva, H.; Valluri, S.; Wu, C.; Larochelle, A.; Dunbar, C.; Young, N.] NHLBI, NIH, Bethesda, MD 20892 USA. [Phillip, S.] Hosp Beneficencia Portuguesa Sao Paulo, Hosp Sao Jose, Sao Paulo, Brazil. [Desmond, R.] Tallaght Hosp, Dublin, Ireland. [Calvo, K.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2015 VL 100 SU 1 MA S826 BP 331 EP 332 PG 2 WC Hematology SC Hematology GA CR3BJ UT WOS:000361204902330 ER PT J AU Mcshane, C Murray, LJ Landgren, O Bradley, MC Hughes, C Anderson, LA AF Mcshane, C. Murray, L. J. Landgren, O. Bradley, M. C. Hughes, C. Anderson, L. A. TI PERSONAL HISTORY OF INFECTIONS ASSOCIATED WITH AN INCREASED RISK OF MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS) AND MULTIPLE MYELOMA: A POPULATION-BASED NESTED CASE-CONTROL STUDY SO HAEMATOLOGICA LA English DT Meeting Abstract CT 20th Congress of European-Hematology-Association CY JUN 11-14, 2015 CL Vienna, AUSTRIA C1 [Mcshane, C.; Murray, L. J.; Anderson, L. A.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. [Landgren, O.] Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, New York, NY 10021 USA. [Bradley, M. C.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Hughes, C.] Queens Univ Belfast, Sch Pharm, Belfast, Antrim, North Ireland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUN PY 2015 VL 100 SU 1 MA E1240 BP 498 EP 498 PG 1 WC Hematology SC Hematology GA CR3BJ UT WOS:000361204903223 ER PT J AU Knutson, KM Dal Monte, O Schintu, S Wassermann, EM Raymont, V Grafman, J Krueger, F AF Knutson, Kristine M. Dal Monte, Olga Schintu, Selene Wassermann, Eric M. Raymont, Vanessa Grafman, Jordan Krueger, Frank TI Areas of Brain Damage Underlying Increased Reports of Behavioral Disinhibition SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID FRONTAL-LOBE DAMAGE; VOXEL-BASED LESION; FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; INHIBITION; CORTEX; APATHY; SELF; DEGENERATION; INTELLIGENCE AB Disinhibition, the inability to inhibit inappropriate behavior, is seen in frontal-temporal degeneration, Alzheimer's disease, and stroke. Behavioral disinhibition leads to social and emotional impairments, including impulsive behavior and disregard for social conventions. The authors investigated the effects of lesions on behavioral disinhibition measured by the Neuropsychiatric Inventory in 177 veterans with traumatic brain injuries. The authors performed voxel-based lesion-symptom mapping using MEDx. Damage in the frontal and temporal lobes, gyrus rectus, and insula was associated with greater behavioral disinhibition, providing further evidence of the frontal lobe's involvement in behavioral inhibition and suggesting that these regions are necessary to inhibit improper behavior. C1 [Knutson, Kristine M.; Wassermann, Eric M.] NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA. [Dal Monte, Olga] Univ Turin, Dept Neuropsychol, Turin, Italy. [Schintu, Selene] INSERM, CNRS, Lyon Neurosci Res Ctr, ImpAct Team,U1028,UMR5292, F-69008 Lyon, France. [Raymont, Vanessa] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England. [Grafman, Jordan] Rehabil Inst Chicago, Brain Injury Res, Chicago, IL 60611 USA. [Grafman, Jordan] Northwestern Univ, Sch Med, Dept Phys Med & Rehabil Psychiat & Behav Sci & Co, Chicago, IL USA. [Krueger, Frank] George Mason Univ, Mol Neurosci Dept, Fairfax, VA 22030 USA. [Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. RP Krueger, F (reprint author), George Mason Univ, Mol Neurosci Dept, Fairfax, VA 22030 USA. EM jgrafman@northwestern.edu; fkrueger@gmu.edu FU U.S. National Institutes of Health, National Institute of Neurological Disorders and Stroke, intramural research program; U.S. Army Medical Research and Material Command [DAMD17-01-1-0675]; National Naval Medical Center FX This work was supported by the U.S. National Institutes of Health, National Institute of Neurological Disorders and Stroke, intramural research program, and a project grant from the U.S. Army Medical Research and Material Command administrated by the Henry M. Jackson Foundation (Grant DAMD17-01-1-0675). The authors thank the Vietnam War veterans who participated in this study; the National Naval Medical Center for support and provision of their facilities; and S. Bonifant, B. Cheon, C. Ngo, A. Greathouse, K. Reding, and G. Tasick for invaluable help with the testing of participants and organization of this study. NR 48 TC 2 Z9 2 U1 2 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 2015 VL 27 IS 3 BP 193 EP 198 DI 10.1176/appi.neuropsych.14060126 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CR7LK UT WOS:000361531000013 PM 25959040 ER PT J AU Wang, Y Cupul-Uicab, LA Rogan, WJ Eggesbo, M Travlos, G Wilson, R Longnecker, MP AF Wang, Yan Cupul-Uicab, Lea A. Rogan, Walter J. Eggesbo, Merete Travlos, Gregory Wilson, Ralph Longnecker, Matthew P. TI Recreational Exercise Before and During Pregnancy in Relation to Plasma C-Reactive Protein Concentrations in Pregnant Women SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE C-reactive protein; pregnancy; the Norwegian Mother and Child Cohort Study; recreational exercise; vigorous-intensity exercise ID GESTATIONAL DIABETES-MELLITUS; TIME PHYSICAL-ACTIVITY; ACUTE-PHASE RESPONSE; CARDIOVASCULAR-DISEASE; NORWEGIAN MOTHER; CHILD COHORT; INFLAMMATORY MARKERS; POSTMENOPAUSAL WOMEN; GLUCOSE-TOLERANCE; PREECLAMPSIA RISK AB Background: Pregnant women who are physically active have a lower risk of preeclampsia and gestational diabetes than women who are less active. One possible mechanism is a reduction in low-grade inflammation, as measured by plasma concentrations of C-reactive protein (CRP). The association between exercise and CRP in pregnant women, however, has not been adequately investigated. Methods: A total of 537 pregnant women, enrolled around the 17th week of gestation in the Norwegian Mother and Child Cohort Study in 2003 to 2004, were studied. Self-reported recreational exercise was recalled for both 3 months before pregnancy and early pregnancy. The total energy expenditure from recreational exercise (total recreational exercise, metabolic equivalent of task [MET]-hr/week) was estimated, and low-, moderate- and vigorous-intensity exercise was defined. Plasma CRP concentrations were measured during pregnancy. Results: In adjusted linear regression models, mean CRP concentration was 1.0% lower [95% CI = -1.9% to 0.2%] with each 1 MET-hr/week of total recreational exercise before pregnancy. In addition, vigorous-intensity exercise before pregnancy was more strongly related to a reduction in CRP levels than low- or moderate-intensity exercise. However, we observed no association between recreational exercise during pregnancy and plasma CRP levels. Conclusions: Recreational exercise before pregnancy, especially vigorous exercise, may reduce the risk of maternal inflammation during pregnancy. C1 [Wang, Yan; Cupul-Uicab, Lea A.; Rogan, Walter J.; Travlos, Gregory; Wilson, Ralph; Longnecker, Matthew P.] NIEHS, US Dept HHS, NIH, Durham, NC 27713 USA. [Cupul-Uicab, Lea A.] Natl Inst Publ Hlth, Populat Res Ctr, Cuernavaca, Morelos, Mexico. [Eggesbo, Merete] Norwegian Inst Publ Hlth, Dept Genes & Environm, Div Epidemiol, Oslo, Norway. RP Wang, Y (reprint author), NIEHS, US Dept HHS, NIH, Durham, NC 27713 USA. EM ywangjian@amail.com; lea.cupul@insp.mx RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; Longnecker, Matthew/0000-0001-6073-5322; Eggesbo, Merete/0000-0002-0006-5336 FU National Institute of Environmental Health Sciences, National Institutes of Health (NIH); Norwegian Ministry of Health; Ministry of Education and Research; National Institute of Environmental Health Sciences [N01-ES75558]; National Institute of Neurological Disorders and Stroke [1UO1-NS047537-01]; Norwegian Research Council/FUGE [151918/S10] FX We are grateful to all the participating families in Norway who take part in this ongoing cohort study. This study was supported in part by the Intramural Research Program, the National Institute of Environmental Health Sciences, National Institutes of Health (NIH). The Norwegian Mother and Child Cohort Study was supported by the Norwegian Ministry of Health and the Ministry of Education and Research, National Institute of Environmental Health Sciences (Contract N01-ES75558), National Institute of Neurological Disorders and Stroke (Grant 1UO1-NS047537-01), and the Norwegian Research Council/FUGE (Grant 151918/S10). NR 47 TC 1 Z9 2 U1 1 U2 6 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JUN PY 2015 VL 12 IS 6 BP 770 EP 775 DI 10.1123/jpah.2013-0390 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR8ZT UT WOS:000361643700006 PM 25111060 ER PT J AU Vladutiu, CJ Evenson, KR Jukic, AM Herring, AH AF Vladutiu, Catherine J. Evenson, Kelly R. Jukic, Anne Marie Herring, Amy H. TI Correlates of Self-Reported Physical Activity at 3 and 12 Months Postpartum SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE leisure activity; women; cohort; longitudinal; pregnancy ID LONGITUDINAL DATA-ANALYSIS; ACTIVITY PATTERNS; WOMEN; PREGNANCY; AVAILABILITY; PREECLAMPSIA; PREDICTORS; RISK AB Background: Postpartum women are encouraged to participate in >= 150 min/week of moderate-intensity aerobic activity, but few women achieve this recommendation. This study sought to identify factors associated with participation in physical activity after pregnancy. Methods: We examined correlates of any self-reported moderate-to-vigorous physical activity (MVPA) (>= 10 min/week across all modes) and any recreational MVPA (>= 10 min/week) among women enrolled in the Pregnancy, Infection, and Nutrition Postpartum study at 3 months postpartum (n = 667) and at 12 months postpartum (n = 530). Potential correlates were identified according to the socioecological framework. Results: At 3 and 12 months postpartum, lower odds of participation in any MVPA were associated with lower education, breastfeeding, and minimal emotional support. Low exercise self-efficacy, receipt of advice about physical activity, and warmer seasons were associated with higher odds of any MVPA. For recreational MVPA, lower odds of participation were associated with unmarried status, lower education, employment, low income, preeclampsia, and minimal emotional support. Involvement in child/adult care activities, transportation MVPA, and warmer seasons were associated with higher odds of recreational MVPA. Conclusion: These findings suggest that several modifiable intrapersonal and interpersonal factors are associated with postpartum MVPA and should be considered when developing interventions to help women maintain or increase MVPA after pregnancy. C1 [Vladutiu, Catherine J.; Evenson, Kelly R.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA. [Jukic, Anne Marie] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Herring, Amy H.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Herring, Amy H.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. RP Vladutiu, CJ (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA. EM vcatheri@email.unc.edu FU National Heart, Lung, and Blood Institute, NIH [T32-HL007055]; National Cancer Institute, NIH [CA109804]; National Institute of Child Health and Human Development, NIH [HD37584]; General Clinical Research Center, NIH [RR00046]; National Institute of Diabetes and Digestive and Kidney Diseases, NIH [DK061981]; Carolina Population Center [R24-HD050924]; Intramural Research Program of the National Institute of Environmental Health Sciences, NIH FX The authors thank Fang Wen from the University of North Carolina at Chapel Hill for her help with data management and Tom Swasey from the Carolina Population Center for his help with the figures. The Pregnancy, Infection, and Nutrition Study is a joint effort of many investigators and staff members whose work is gratefully acknowledged. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH). CJV received financial support from grant T32-HL007055 from the National Heart, Lung, and Blood Institute, NIH. Funding for the study was provided by the National Cancer Institute, NIH (CA109804). Data collected were supported by the National Institute of Child Health and Human Development, NIH (HD37584), General Clinical Research Center, NIH (RR00046), and National Institute of Diabetes and Digestive and Kidney Diseases, NIH (DK061981). Support was also received from the Carolina Population Center (R24-HD050924). AMJ was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, NIH. NR 33 TC 1 Z9 1 U1 1 U2 2 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JUN PY 2015 VL 12 IS 6 BP 814 EP 822 DI 10.1123/jpah.2014-0147 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR8ZT UT WOS:000361643700013 PM 25157810 ER PT J AU Oh, AY Hennessy, E McSpadden, KE Perna, FM AF Oh, April Y. Hennessy, Erin McSpadden, Kate E. Perna, Frank M. TI Contextual Influences on Weight Status Among Impoverished Adolescents: Neighborhood Amenities for Physical Activity and State Laws for Physical Education Time Requirements SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE obesity; overweight; policy; low social class ID OBESITY; ENVIRONMENT; CHILDHOOD; SCHOOLS; YOUTH AB Purpose: This study examines the relationship between state laws for physical education and neighborhood amenities for physical activity on weight status in adolescents of low socioeconomic status. Methods: Data from 2 national data sources: Classification of Laws Associated with School Students (CLASS) and the National Survey of Children's Health (NSCH) were combined and analyzed. Results: Multinomial regression models found that adolescents in states with strong PE law were associated with a lower odds of being obese [OR = 0.63 (0.41, 0.97)1; however, when PE law and neighborhood amenities were included, only neighborhood amenities were associated with lower odds of obesity, but also greater odds of overweight status. Conclusions: This study emphasizes the potential significance of state laws on low SES groups to combat obesity; as well as the potential differential effects of local level factors, and alignment with policy goals for healthy weight. C1 [Oh, April Y.; Perna, Frank M.] NCI, Div Canc Control & Populat Sci, Hlth Commun & Informat Res Branch, Rockville, MD 20852 USA. [Hennessy, Erin] Leidos Biomed Res Inc, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [McSpadden, Kate E.] Catholic Univ Amer, Natl Catholic Sch Social Serv, Washington, DC 20064 USA. RP Oh, AY (reprint author), NCI, Div Canc Control & Populat Sci, Hlth Commun & Informat Res Branch, Rockville, MD 20852 USA. EM ohay@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 22 TC 0 Z9 0 U1 1 U2 4 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JUN PY 2015 VL 12 IS 6 BP 875 EP 878 DI 10.1123/jpah.2013-0303 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR8ZT UT WOS:000361643700020 PM 25109235 ER PT J AU Hong, C Piazza, M Ho, W Zhuang, ZP AF Hong, Christopher Piazza, Martin Ho, Winson Zhuang, Zhengping TI DISRUPTION OF PERIVASCULAR ASTROCYTIC FOOT PROCESSES CHARACTERIZES MRI ENHANCEMENT IN PEDIATRIC BRAIN TUMORS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 3rd Biennial Conference on Pediatric Neuro-Oncology Basic and Translational Research CY MAY 07-08, 2015 CL San Diego, CA C1 [Hong, Christopher; Piazza, Martin; Ho, Winson; Zhuang, Zhengping] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2015 VL 17 SU 3 MA BI-02 BP 2 EP 2 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4LV UT WOS:000361304800009 ER PT J AU Grasso, CS Tang, YJ Truffaux, N Berlow, NE Liu, LN Debily, MA Quist, MJ Davis, L Huang, EC Woo, PJ Ponnuswami, A Chen, S Johung, T Sun, WC Kogiso, M Du, YC Lin, Q Huang, YL Hutt-Cabezas, M Warren, KE Le Dret, L Meltzer, PS Mao, H Quezado, M van Vuurden, DG Abraham, J Fouladi, M Svalina, MN Wang, N Hawkins, C Raabe, E Hulleman, E Spellman, PT Li, XN Keller, C Pal, R Grill, J Monje, M AF Grasso, Catherine S. Tang, Yujie Truffaux, Nathalene Berlow, Noah E. Liu, Lining Debily, Marie-Anne Quist, Michael J. Davis, Lara Huang, Elaine C. Woo, Pamelyn J. Ponnuswami, Anitha Chen, Spenser Johung, Tessa Sun, Wenchao Kogiso, Mari Du, Yuchen Lin, Qi Huang, Yulun Hutt-Cabezas, Marianne Warren, Katherine E. Le Dret, Ludivine Meltzer, Paul S. Mao, Hua Quezado, Martha van Vuurden, Dannis G. Abraham, Jinu Fouladi, Maryam Svalina, Matthew N. Wang, Nicholas Hawkins, Cynthia Raabe, Eric Hulleman, Esther Spellman, Paul T. Li, Xiao-Nan Keller, Charles Pal, Ranadip Grill, Jacques Monje, Michelle TI FUNCTIONALLY-DEFINED THERAPEUTIC TARGETS IN DIFFUSE INTRINSIC PONTINE GLIOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 3rd Biennial Conference on Pediatric Neuro-Oncology Basic and Translational Research CY MAY 07-08, 2015 CL San Diego, CA C1 [Grasso, Catherine S.; Quist, Michael J.; Wang, Nicholas; Spellman, Paul T.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Ctr Spatial Syst Biomed, Portland, OR 97201 USA. [Tang, Yujie; Liu, Lining; Woo, Pamelyn J.; Ponnuswami, Anitha; Chen, Spenser; Johung, Tessa; Sun, Wenchao; Monje, Michelle] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. [Tang, Yujie; Liu, Lining; Woo, Pamelyn J.; Ponnuswami, Anitha; Chen, Spenser; Johung, Tessa; Sun, Wenchao; Monje, Michelle] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA. [Tang, Yujie; Liu, Lining; Woo, Pamelyn J.; Ponnuswami, Anitha; Chen, Spenser; Johung, Tessa; Sun, Wenchao; Monje, Michelle] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Truffaux, Nathalene; Debily, Marie-Anne; Le Dret, Ludivine; Grill, Jacques] Inst Gustave Roussy, CNRS, UMR 8203, Villejuif, France. [Berlow, Noah E.; Pal, Ranadip] Texas Tech Univ, Elect & Comp Engn, Lubbock, TX 79409 USA. [Debily, Marie-Anne] Univ Evry Val dEssone, Evry, France. [Davis, Lara; Huang, Elaine C.; Abraham, Jinu; Svalina, Matthew N.; Keller, Charles] Oregon Hlth & Sci Univ, Pape Family Pediat Res Inst, Pediat Canc Biol Program, Dept Pediat, Portland, OR 97201 USA. [Davis, Lara; Huang, Elaine C.; Abraham, Jinu; Svalina, Matthew N.; Keller, Charles] Childrens Canc Therapy Dev Inst, Ft Collins, CO USA. [Kogiso, Mari; Du, Yuchen; Lin, Qi; Huang, Yulun; Mao, Hua; Li, Xiao-Nan] Baylor Coll Med, Texas Childrens Canc Ctr, Mol Neurooncol Lab, Houston, TX 77030 USA. [Huang, Yulun] First Affiliated Hosp Soochow, Dept Neurosurg, Suzhou, Peoples R China. [Hutt-Cabezas, Marianne; Raabe, Eric] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Hutt-Cabezas, Marianne; Raabe, Eric] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Warren, Katherine E.; Meltzer, Paul S.; Quezado, Martha] NCI, Bethesda, MD 20892 USA. [van Vuurden, Dannis G.; Hulleman, Esther] Vrije Univ Amsterdam Med Ctr, Hematol & Neurooncol Res Grp, Canc Ctr Amsterdam, Dept Pediat Oncol, Amsterdam, Netherlands. [Fouladi, Maryam] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA. [Hawkins, Cynthia] Univ Toronto, Dept Paediat Lab Med, Toronto, ON, Canada. [Hawkins, Cynthia] Univ Toronto, Hosp Sick Children, Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada. [Grill, Jacques] Univ Paris 11, Inst Gustave Roussy, Dept Cancerol Enfant & Adolescent, Villejuif, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2015 VL 17 SU 3 MA BT-02 BP 3 EP 3 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4LV UT WOS:000361304800013 ER PT J AU Hong, C Hao, SY Feng, J Yang, CZ Chittiboina, P Zhang, JT Zhuang, ZP AF Hong, Christopher Hao, Shuyu Feng, Jie Yang, Chunzhang Chittiboina, Prashant Zhang, Junting Zhuang, Zhengping TI IDH1-MUTATED PITUITARY ADENOMA CHALLENGES TRADITIONAL CHARACTERIZATION OF MAFFUCCI SYNDROME SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 3rd Biennial Conference on Pediatric Neuro-Oncology Basic and Translational Research CY MAY 07-08, 2015 CL San Diego, CA C1 [Hong, Christopher; Yang, Chunzhang; Chittiboina, Prashant; Zhuang, Zhengping] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. [Hao, Shuyu; Feng, Jie] Capital Med Univ, Beijing Tiantan Hosp, Beijing, Peoples R China. [Zhang, Junting] Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2015 VL 17 SU 3 MA GE-01 BP 7 EP 7 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4LV UT WOS:000361304800026 ER PT J AU Hoffman, LM Bartels, U Miles, L Hawkins, C Goldman, S Leary, S Hassal, T Minturn, J Packer, R Foreman, N Warren, K Broniscer, A Broxon, E Shih, CS Leach, J Jones, B Baugh, J Hacker, B Lerme, B Jones, C Savage, S Kirkendall, J Doughman, R Wollman, M Millett, L O'Keefe, R Bouffet, E van Vuurden, DG Fouladi, M AF Hoffman, Lindsey M. Bartels, Ute Miles, Lili Hawkins, Cynthia Goldman, Stewart Leary, Sarah Hassal, Tim Minturn, Jane Packer, Roger Foreman, Nicholas Warren, Kathy Broniscer, Alberto Broxon, Emmett Shih, Chie-Schin Leach, James Jones, Blaise Baugh, Josh Hacker, Brooklyn Lerme, Brianna Jones, Chris Savage, Sharon Kirkendall, Jenavieve Doughman, Renee Wollman, Matt Millett, Linwood O'Keefe, Rachel Bouffet, Eric van Vuurden, Dannis G. Fouladi, Maryam TI CLINICAL, RADIOGRAPHIC, AND HISTOLOGIC CHARACTERISTICS OF LONG-TERM SURVIVORS OF DIFFUSE INTRINSIC PONTINE GLIOMA: A REPORT FROM THE INTERNATIONAL DIPG REGISTRY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 3rd Biennial Conference on Pediatric Neuro-Oncology Basic and Translational Research CY MAY 07-08, 2015 CL San Diego, CA C1 [Hoffman, Lindsey M.; Miles, Lili; Leach, James; Jones, Blaise; Baugh, Josh; Hacker, Brooklyn; Lerme, Brianna; Kirkendall, Jenavieve; Doughman, Renee; Wollman, Matt; Millett, Linwood; O'Keefe, Rachel; Fouladi, Maryam] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Bartels, Ute; Hawkins, Cynthia; Bouffet, Eric] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Goldman, Stewart] Lurie Childrens Hosp, Chicago, IL USA. [Leary, Sarah] Seattle Childrens Hosp, Seattle, WA USA. [Hassal, Tim] Lady Cilento Childrens Hosp, Brisbane, Qld, Australia. [Minturn, Jane] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Foreman, Nicholas] Childrens Hosp Colorado, Denver, CO USA. [Warren, Kathy; Savage, Sharon] NIH, Bethesda, MD 20892 USA. [Broniscer, Alberto] St Jude Childrens Res Hosp, Med Ctr, Memphis, TN USA. [Broxon, Emmett] Dayton Childrens Hosp, Dayton, OH USA. [Shih, Chie-Schin] Riley Childrens Hosp, Indianapolis, IN USA. [van Vuurden, Dannis G.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Jones, Chris] Inst Canc Res, Sutton, Surrey, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2015 VL 17 SU 3 MA HG-14 BP 13 EP 13 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4LV UT WOS:000361304800052 ER PT J AU Feldman, M Ho, W Heiss, J Hall, M Zhuang, ZP AF Feldman, Michael Ho, Winson Heiss, John Hall, Matthew Zhuang, Zhenping TI INDUCED CISPLATIN RESISTANCE IN MEDULLOBLASTOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 3rd Biennial Conference on Pediatric Neuro-Oncology Basic and Translational Research CY MAY 07-08, 2015 CL San Diego, CA C1 [Feldman, Michael; Ho, Winson; Heiss, John; Zhuang, Zhenping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Feldman, Michael] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Hall, Matthew] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2015 VL 17 SU 3 MA MB-12 BP 22 EP 22 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4LV UT WOS:000361304800089 ER PT J AU Ho, SCW Feldman, M Maric, D Heiss, J Zhuang, ZP AF Ho, Sze Chun Winson Feldman, Michael Maric, Dragan Heiss, John Zhuang, Zhengping TI LB100, A NOVEL PROTEIN PHOSPHATASE 2A INHIBITOR, ENHANCES CISPLATIN AND RADIATION MEDIATED CYTOTOXICITY AND OVERCOME CISPLATIN RESISTANCE IN-VITRO SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 3rd Biennial Conference on Pediatric Neuro-Oncology Basic and Translational Research CY MAY 07-08, 2015 CL San Diego, CA C1 [Ho, Sze Chun Winson; Feldman, Michael; Maric, Dragan; Heiss, John; Zhuang, Zhengping] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2015 VL 17 SU 3 MA TR-07 BP 38 EP 38 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4LV UT WOS:000361304800153 ER PT J AU Demers, LM Hankinson, SE Haymond, S Key, T Rosner, W Santen, RJ Stanczyk, FZ Vesper, HW Ziegler, RG AF Demers, L. M. Hankinson, S. E. Haymond, S. Key, T. Rosner, W. Santen, R. J. Stanczyk, F. Z. Vesper, H. W. Ziegler, R. G. TI Measuring Estrogen Exposure and Metabolism: Workshop Recommendations on Clinical Issues SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POSTMENOPAUSAL WOMEN; ESTRADIOL LEVELS; SERUM ESTRADIOL; STATEMENT C1 [Demers, L. M.] Penn State Univ, Sch Med, Dept Pathol, Hershey, PA 17003 USA. [Demers, L. M.] Penn State Univ, Sch Med, Dept Med, Hershey, PA 17003 USA. [Hankinson, S. E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Haymond, S.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Key, T.] Univ Oxford, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England. [Rosner, W.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Santen, R. J.] Univ Virginia Hlth Sci Syst, Div Endocrinol & Metab, Charlottesville, VA 22903 USA. [Stanczyk, F. Z.] Univ So Calif, Keck Sch Med, Dept Obstet Gynecol, Los Angeles, CA 90033 USA. [Stanczyk, F. Z.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Vesper, H. W.] Ctr Dis Control & Prevent, Div Sci Lab, Atlanta, GA 30333 USA. [Ziegler, R. G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Demers, LM (reprint author), Penn State Univ Pathol, 1175 Stonegate Rd, Hummelstown, PA 17036 USA. EM lmd4@psu.edu FU Intramural Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute, the National Institutes of Health; CDC Foundation; American Association for Clinical Chemistry; Endocrine Society; ARUP Laboratories; Beckman Coulter, Inc; inVentiv Health; Quest Diagnostics FX Appreciation is expressed for financial support for the meeting provided by the Intramural Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute, the National Institutes of Health; the CDC Foundation; the American Association for Clinical Chemistry; The Endocrine Society; ARUP Laboratories; Beckman Coulter, Inc; inVentiv Health; and Quest Diagnostics. NR 14 TC 5 Z9 5 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2015 VL 100 IS 6 BP 2165 EP 2170 DI 10.1210/jc.2015-1040 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ8ET UT WOS:000360840000027 PM 25850026 ER PT J AU Chaker, L Baumgartner, C den Elzen, WPJ Ikram, MA Blum, MR Collet, TH Bakker, SJL Dehghan, A Drechsler, C Luben, RN Hofman, A Portegies, MLP Medici, M Iervasi, G Stott, DJ Ford, I Bremner, A Wanner, C Ferrucci, L Newman, AB Dullaart, RP Sgarbi, JA Ceresini, G Maciel, RMB Westendorp, RG Jukema, JW Imaizumi, M Franklyn, JA Bauer, DC Walsh, JP Razvi, S Khaw, KT Cappola, AR Volzke, H Franco, OH Gussekloo, J Rodondi, N Peeters, RP AF Chaker, Layal Baumgartner, Christine den Elzen, Wendy P. J. Ikram, M. Arfan Blum, Manuel R. Collet, Tinh-Hai Bakker, Stephan J. L. Dehghan, Abbas Drechsler, Christiane Luben, Robert N. Hofman, Albert Portegies, Marileen L. P. Medici, Marco Iervasi, Giorgio Stott, David J. Ford, Ian Bremner, Alexandra Wanner, Christoph Ferrucci, Luigi Newman, Anne B. Dullaart, Robin P. Sgarbi, Jose A. Ceresini, Graziano Maciel, Rui M. B. Westendorp, Rudi G. Jukema, J. Wouter Imaizumi, Misa Franklyn, Jayne A. Bauer, Douglas C. Walsh, John P. Razvi, Salman Khaw, Kay-Tee Cappola, Anne R. Voelzke, Henry Franco, Oscar H. Gussekloo, Jacobijn Rodondi, Nicolas Peeters, Robin P. CA Thyroid Studies Collaboration TI Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID ISCHEMIC-HEART-DISEASE; UNITED-STATES POPULATION; THYROID-DYSFUNCTION; CARDIOVASCULAR RISK; OSTEOPOROTIC FRACTURES; MYOCARDIAL-INFARCTION; SERUM THYROTROPIN; NATIONAL-HEALTH; OLDER MEN; ALL-CAUSE AB Objective: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T-4 levels. Data Extraction and Synthesis: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 personyears). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or >= 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. Conclusions: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed. C1 [Chaker, Layal; Medici, Marco; Peeters, Robin P.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. Erasmus MC, Rotterdam Thyroid Ctr, NL-3000 CA Rotterdam, Netherlands. [Chaker, Layal; Ikram, M. Arfan; Dehghan, Abbas; Hofman, Albert; Portegies, Marileen L. P.; Franco, Oscar H.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Baumgartner, Christine; Blum, Manuel R.; Rodondi, Nicolas] Univ Hosp Bern, Inselspital, Dept Gen Internal Med, CH-3010 Bern, Switzerland. [den Elzen, Wendy P. J.; Gussekloo, Jacobijn] Leiden Univ, Med Ctr, Dept Epidemiol, NL-2333 ZA Leiden, Netherlands. [den Elzen, Wendy P. J.; Gussekloo, Jacobijn] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2333 ZA Leiden, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, NL-3000 CA Rotterdam, Netherlands. [Ikram, M. Arfan; Portegies, Marileen L. P.] Erasmus Univ, Med Ctr, Dept Neurol, NL-3000 CA Rotterdam, Netherlands. [Collet, Tinh-Hai] Univ Lausanne Hosp, Serv Endocrinol Diabet & Metab, CH-1011 Lausanne, Switzerland. [Bakker, Stephan J. L.; Dullaart, Robin P.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, NL-9700 RB Groningen, Netherlands. [Drechsler, Christiane; Wanner, Christoph] Univ Hosp Wurzburg, Germany Comprehens Heart Failure Ctr, Div Nephrol, Dept Med, D-97080 Wurzburg, Germany. [Luben, Robert N.; Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Iervasi, Giorgio] CNR, Inst Clin Physiol, I-56124 Pisa, Italy. [Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8QQ, Lanark, Scotland. [Bremner, Alexandra] Univ Western Australia, Sch Populat Hlth, Crawley, WA 6009, Australia. [Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Sgarbi, Jose A.] Fac Med Marilia, Div Endocrinol, BR-17519 Sao Paulo, Brazil. [Sgarbi, Jose A.; Maciel, Rui M. B.] Univ Fed Sao Paulo, Dept Med, Div Endocrinol, BR-04021001 Sao Paulo, Brazil. [Ceresini, Graziano] Univ Parma, Dept Clin & Expt Med, I-43125 Parma, Italy. [Westendorp, Rudi G.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, DK-1165 Copenhagen, Denmark. [Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, NL-2333 ZA Leiden, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, NL-3511 EP Utrecht, Netherlands. [Imaizumi, Misa] Radiat Effects Res Fdn, Dept Clin Studies, Nagasaki 8500013, Japan. [Franklyn, Jayne A.] Univ Birmingham, Coll Med & Dent Sci, Sch Clin & Expt Med, Birmingham B15 2TT, W Midlands, England. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Biostat & Med, San Francisco, CA 94143 USA. [Walsh, John P.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia. [Walsh, John P.] Univ Western Australia, Sch Med, Crawley, WA 6009, Australia. [Walsh, John P.] Univ Western Australia, Sch Pharmacol, Crawley, WA 6009, Australia. [Razvi, Salman] Gateshead Hlth Fdn NHS Trust, Dept Endocrinol, Gateshead NE9 6SX, England. [Cappola, Anne R.] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Voelzke, Henry] Univ Med, Clin Epidemiol Research SHIP, Inst Community Med, D-17489 Greifswald, Germany. RP Peeters, RP (reprint author), Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam Thyroid Ctr, Room Ee 500,POB 2040, NL-3000 CA Rotterdam, Netherlands. EM r.peeters@erasmusmc.nl RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Luben, Robert/0000-0002-5088-6343; Blum, Manuel/0000-0003-4638-775X; Razvi, Salman/0000-0002-9047-1556; Dehghan, Abbas/0000-0001-6403-016X; Collet, Tinh-Hai/0000-0002-3243-1222 FU Erasmus MC Medical Research Advisory Committee grant; ZonMW TOP Grant [21.12.044]; Genzyme B.V.; Swiss National Science Foundation [320030-138267, 320030-150025, SNSF 320030-138267, PBLAP3-145870]; Erasmus MCMRACE grant; ZonMW TOPgrant [21.12.044]; Swiss Foundation for Grants in Biology and Medicine [P3SMP3-155318]; National Institute on Aging (NIA) [R01AG032317, K24AG042765, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute of Neurological Disorders and Stroke (NINDS); NIA [AG023629, 19]; NINR [R01-NR012459]; Research Network of Community Medicine; German Research Foundation [DFG Vo 955/12-1]; Japanese Ministry of Health, Labour and Welfare (MHLW); US Department of Energy (DOE); DOE [DE-HS0000031]; Sao Paulo State Research Foundation (Fundacao de Amaparo a Pesquisa do Estado de Sao Paulo, FAPESP) [6/59737-9]; Dutch Kidney Foundation [E.033]; Dade Behring; Ausam; Roche; Abbott; Dutch Heart Foundation [2001-005]; National Institutes of Health funding; National Institute on Aging (NIA); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Advancing Translational Sciences (NCATS); NIH Roadmap for Medical Research [U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128] FX This study was supported by an Erasmus MC Medical Research Advisory Committee grant and ZonMW TOP Grant 21.12.044 (to R.P.P.). R.P.P. has received lecture and consultancy fees from Genzyme B.V. The Thyroid Studies Collaboration is supported by grants from the Swiss National Science Foundation (320030-138267 and 320030-150025; to N.R.).; The study was supported by an Erasmus MCMRACE grant and a ZonMW TOPgrant (21.12.044) to Dr. R. P. Peeters. Dr. R.P. Peeters has received lecture and consultancy fees from Genzyme B.V. The Thyroid Studies Collaboration is supported by a grant from the Swiss National Science Foundation (SNSF 320030-138267 and 320030-150025 to Prof. N. Rodondi). Dr. T-H Collet's research is supported by grants from the Swiss National Science Foundation (PBLAP3-145870) and the Swiss Foundation for Grants in Biology and Medicine (P3SMP3-155318). The Cardiovascular Health Study (CHS) was supported by R01AG032317 and K24AG042765 from the National Institute on Aging (NIA), contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG023629,19 from the NIA. A full list of principal CHS investigators and institutions can be found at CH NHLBI.org. The Health ABC Study was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and NINR grant R01-NR012459. SHIP data collection and analysis were supported by the Research Network of Community Medicine and the German Research Foundation (DFG Vo 955/12-1). The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan is a public interest foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the US Department of Energy (DOE). The research was also funded in part through DOE award DE-HS0000031 to the National Academy of Sciences. The Brazilian Thyroid Study was supported by an unrestricted grant from the Sao Paulo State Research Foundation (Fundacao de Amaparo a Pesquisa do Estado de Sao Paulo, FAPESP, grant 6/59737-9 to Dr Maciel). The Dutch Kidney Foundation supported the infrastructure of the PREVEND program from 1997 to 2003 (Grant E.033). The University Medical Center Groningen supported the infrastructure from 2003 to 2006. Dade Behring, Ausam, Roche, and Abbott financed laboratory equipment and reagents by which various laboratory determinations could be performed. The Dutch Heart Foundation supported studies on lipid metabolism (Grant 2001-005). The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. NR 69 TC 13 Z9 13 U1 1 U2 15 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2015 VL 100 IS 6 BP 2181 EP 2191 DI 10.1210/jc.2015-1438 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ8ET UT WOS:000360840000029 PM 25856213 ER PT J AU Polotsky, AJ Allshouse, AA Casson, PR Coutifaris, C Diamond, MP Christman, GM Schlaff, WD Alvero, R Trussell, JC Krawetz, SA Santoro, N Eisenberg, E Zhang, HP Legro, RS AF Polotsky, Alex J. Allshouse, Amanda A. Casson, Peter R. Coutifaris, Christos Diamond, Michael P. Christman, Gregory M. Schlaff, William D. Alvero, Ruben Trussell, J. C. Krawetz, Stephen A. Santoro, Nanette Eisenberg, Esther Zhang, Heping Legro, Richard S. TI Impact of Male and Female Weight, Smoking, and Intercourse Frequency on Live Birth in Women With Polycystic Ovary Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; BASE-LINE CHARACTERISTICS; MATERNAL OBESITY; CONSORT STATEMENT; CLINICAL-TRIALS; INFERTILITY; OVERWEIGHT; PREGNANCY; RISK; MEN AB Context: Obese men with normal semen parameters exhibit reduced fertility but few prospective data are available. Objective: This study aimed to determine the effect of male factors and body mass among the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) participants. Methods: This is a secondary analysis of the PPCOS II trial. A total of 750 infertile women with polycystic ovary syndrome (PCOS) were randomly assigned to up to receive five cycles of letrozole or clomiphene citrate. Females were 18-39-years-old and had a male partner with sperm concentration of at least 14 million/mL who consented to regular intercourse. Analysis was limited to couples with complete male partner information (n = 710). Results: Male body mass index (BMI) was higher in couples who failed to conceive (29.5 kg/m(2) vs 28.2 kg/m(2); P = .039) as well as those who did not achieve a live birth (29.5 kg/m(2) vs 28.1 kg/m(2); P = .047). At least one partner was obese in 548 couples (77.1%). A total of 261 couples were concordant for obesity (36.8%). After adjustment for female BMI, the association of male BMI with live birth was no longer significant (odds ratio [OR] = 0.85; 95% confidence interval [CI], 0.68-1.05; P = .13). Couples in which both partners smoked had a lower chance of live birth vs nonsmokers (OR = 0.20; 95% CI, 0.08-0.52; P = .02), whereas there was not a significant effect of female or male smoking alone. Live birth was more likely in couples with at least three sexual intercourse attempts over the previous 4 weeks (reported at baseline) as opposed to couples with lesser frequency (OR = 4.39; 95% CI, 1.52-12. 4; P = .01). Conclusions: In this large cohort of obese women with PCOS, effect of male obesity was explained by female BMI. Lower chance of success was seen among couples where both partners smoked. Obesity and smoking are common among women with PCOS and their partners and contribute to a decrease in fertility treatment success. C1 [Polotsky, Alex J.; Allshouse, Amanda A.; Alvero, Ruben; Santoro, Nanette] Univ Colorado Denver, Dept Obstet & Gynecol, Aurora, CO 80045 USA. [Allshouse, Amanda A.] Univ Colorado Denver, Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO 80045 USA. [Casson, Peter R.] Univ Vermont, Dept Obstet & Gynecol, Burlington, VT 05405 USA. [Coutifaris, Christos] Hosp Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Diamond, Michael P.] GA Regents Univ, Dept Obstet & Gynecol, Augusta, GA 30912 USA. [Christman, Gregory M.] Univ Florida Hlth Syst, Dept Obstet & Gynecol, Gainesville, FL 32610 USA. [Schlaff, William D.] Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. [Trussell, J. C.] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13202 USA. [Krawetz, Stephen A.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Eisenberg, Esther] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Zhang, Heping] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06520 USA. [Legro, Richard S.] Penn State Coll Med, Dept Obstet & Gynecol, Hershey, PA 17033 USA. RP Polotsky, AJ (reprint author), Univ Colorado Denver, Dept Obstet & Gynecol, 12631 East 17th Ave,Mail Stop B198-3, Aurora, CO 80045 USA. EM alex.polotsky@ucdenver.edu OI Diamond, Michael/0000-0001-6353-4489 FU Eunice Shriver National Institute of Child Health and Human Development [U10HD27049U10 HD38998, U10 HD38992, U10HD055925, U10 HD39005, U10 HD055936, U10 HD33172, U10 HD38998, U10 HD055944]; [U54-HD29834] FX This work was supported by the Eunice Shriver National Institute of Child Health and Human Development. U10HD27049 (to C.C.), U10 HD38992 (to R.S.L.), U10HD055925 (to H.Z.), U10 HD39005 (to M.P.D.), U10 HD055936 (to G.M.C.), U10 HD33172, U10 HD38998 (to R.A.), and U10 HD055944 (to P.R.C.); and U54-HD29834 (to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core of the Specialized Cooperative Centers Program in Reproduction and Infertility Research). NR 42 TC 4 Z9 4 U1 1 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2015 VL 100 IS 6 BP 2405 EP 2412 DI 10.1210/jc.2015-1178 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ8ET UT WOS:000360840000055 PM 25856211 ER PT J AU Espiard, S Drougat, L Libe, R Assie, G Perlemoine, K Guignat, L Barrande, G Brucker-Davis, F Doullay, F Lopez, S Sonnet, E Torremocha, F Pinsard, D Chabbert-Buffet, N Raffin-Sanson, ML Groussin, L Borson-Chazot, F Coste, J Bertagna, X Stratakis, CA Beuschlein, F Ragazzon, B Bertherat, J AF Espiard, Stephanie Drougat, Ludivine Libe, Rossella Assie, Guillaume Perlemoine, Karine Guignat, Laurence Barrande, Gaelle Brucker-Davis, Francoise Doullay, Francoise Lopez, Stephanie Sonnet, Emmanuel Torremocha, Florence Pinsard, Denis Chabbert-Buffet, Nathalie Raffin-Sanson, Marie-Laure Groussin, Lionel Borson-Chazot, Franoise Coste, Joel Bertagna, Xavier Stratakis, Constantine A. Beuschlein, Felix Ragazzon, Bruno Bertherat, Jerome TI ARMC5 Mutations in a Large Cohort of Primary Macronodular Adrenal Hyperplasia: Clinical and Functional Consequences SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NODULAR ADRENOCORTICAL DISEASE; SUBCLINICAL CUSHINGS-SYNDROME; CORTISOL SECRETION; HORMONE-RECEPTORS; GENE; VASOPRESSIN; FREQUENT; MINERALOCORTICOIDS; CORTICOTROPIN; HETEROGENEITY AB Context: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of primary adrenal Cushing's syndrome (CS). ARMC5 germline mutations have been identified recently in PBMAH. Objective: To determine the prevalence of ARMC5 mutations and analyze genotype-phenotype correlation in a large cohort of unrelated PBMAH patients with subclinical or clinical CS. Patients and Methods: ARMC5 was sequenced in 98 unrelated PBMAH index cases. PBMAH was identified by bilateral adrenal nodular enlargement on computed tomography scan. The effect on apoptosis of ARMC5 missense mutants was tested in H295R and HeLa cells. Clinical and hormonal data were collected including midnight and urinary free cortisol levels, ACTH, androgens, renin/aldosterone ratio, cortisol after overnight dexamethasone suppression test, cortisol and 17-hydroxyprogesterone after ACTH 1-24 stimulation and illegitimate receptor responses. Computed tomography and histological reports were analyzed. Results: ARMC5-damaging mutations were identified in 24 patients (26%). The missense mutants and the p.F700del deletion were unable to induce apoptosis in both H295R and HeLa cell lines, unlike the wild-typegene. ARMC5-mutated patients showed an overt CS more frequently, compared to wild-type patients: lower ACTH, higher midnight plasma cortisol, urinary free cortisol, and cortisol after dexamethasone suppression test (P = .003,.019,.006, and <.001, respectively). Adrenals of patients with mutations were bigger and had a higher number of nodules (P = .001 and <.001, respectively). Conclusions: ARMC5 germline mutations are common in PBMAH. Index cases of mutation carriers show a more severe hypercortisolism and larger adrenals. ARMC5 genotyping may help to identify clinical forms of PBMAH better and may also allow earlier diagnosis of this disease. C1 [Espiard, Stephanie; Drougat, Ludivine; Libe, Rossella; Assie, Guillaume; Perlemoine, Karine; Groussin, Lionel; Ragazzon, Bruno; Bertherat, Jerome] Inst Cochin Genet Mol, INSERM, U1016, F-75014 Paris, France. [Espiard, Stephanie; Drougat, Ludivine; Libe, Rossella; Assie, Guillaume; Perlemoine, Karine; Groussin, Lionel; Ragazzon, Bruno; Bertherat, Jerome] CNRS, UMR 8104, F-75014 Paris, France. [Espiard, Stephanie; Drougat, Ludivine; Libe, Rossella; Assie, Guillaume; Perlemoine, Karine; Groussin, Lionel; Ragazzon, Bruno; Bertherat, Jerome] Univ Paris 05, Sorbonne Paris Cite, F-75013 Paris, France. [Libe, Rossella; Assie, Guillaume; Guignat, Laurence; Groussin, Lionel; Bertagna, Xavier; Bertherat, Jerome] Hop Cochin, AP HP, Referral Ctr Rare Adrenal Dis, Dept Endocrinol, F-75014 Paris, France. [Barrande, Gaelle] Reg Hosp Orleans, Dept Endocrinol, F-45032 Orleans, France. [Brucker-Davis, Francoise] Univ Hosp Nice, Dept Endocrinol Diabetol & Reprod Med, F-06200 Nice, France. [Doullay, Francoise] Hop Nord Marseille, Assistance Publ Hop Marseille, Dept Endocrinol, F-13915 Marseille, France. [Lopez, Stephanie] Univ Hosp Limoges, Dept Internal Med Endocrinol & Metab Dis B, F-87042 Limoges, France. [Sonnet, Emmanuel] Univ Hosp Brest, Hop Cavale Blanche, Dept Endocrinol, F-29609 Brest, France. [Torremocha, Florence] Univ Hosp Poitiers, Dept Internal Med & Endocrinol, F-86021 Poitiers, France. [Pinsard, Denis] Hop Sud, Ctr Hosp Univ Rennes, Dept Endocrinol, F-35203 Rennes, France. [Chabbert-Buffet, Nathalie] Hop Tenon, AP HP, Unit Endocrinol Obstet Gynecol & Reprod Med, Dept, F-75020 Paris, France. [Raffin-Sanson, Marie-Laure] CHU Ambroise Pare, AP HP, Dept Endocrinol, F-92100 Boulogne, France. Univ Versailles St Quentin, EA2394, F-92100 Boulogne, France. [Borson-Chazot, Franoise] Hosp Civils Lyon, INSERM, U1052, Dept Endocrinol Lyon Est, F-69677 Bron, France. Univ Lyon, F-69677 Bron, France. [Coste, Joel] Hop Hotel Dieu, AP HP, Biostat & Epidemiol Unit, Paris, France. [Coste, Joel] Univ Paris 05, Lorraine Univ, Res Unit APEMAC, EA 4360, F-75006 Paris, France. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Beuschlein, Felix] Klinikum Univ Munchen, Med Klin & Poliklin 4, D-80336 Munich, Germany. RP Bertherat, J (reprint author), Hop Cochin, Ctr Reference Malad Rares Surrenale, Serv Malad Endocriniennes & Metab, 27 Rue Faubourg St Jacques, F-75014 Paris, France. EM jerome.bertherat@cch.aphp.fr RI Ragazzon, Bruno/E-6541-2017; OI Ragazzon, Bruno/0000-0001-9476-4973; Borson-Chazot, Francoise/0000-0003-2515-7840 FU Agence Nationale de la Recherche [ANR-10-Blan-1136]; COMETE Network, Programme Hospitalier de Recherche Clinique Grant [AOM95201]; Assistance Publique-Hopitaux de Paris (Clinical Research Center Grant Genhyper) [P061006]; ENSAT-CANCER (FP7 program) [Health-F2-2010-259735]; Inserm; E-RARE program (Genomics of cAMP signaling alterations in adrenal Cushing project),; Conny-Maeva Charitable Foundation; Brou de Lauriere Fondation; Intramural Program of the Eunice Kennedy Shriver, National Institute of Child Health & Human Development [Z01 HD008920-04] FX This study was supported in part by the Agence Nationale de la Recherche (ANR-10-Blan-1136), the COMETE Network, Programme Hospitalier de Recherche Clinique Grant AOM95201, the Assistance Publique-Hopitaux de Paris (Clinical Research Center Grant Genhyper P061006), ENSAT-CANCER Health-F2-2010-259735 (FP7 program), Inserm (S.E. is receiving a Poste Accueil, and G.A. is receiving a Contrat d'Interface), the E-RARE program (Genomics of cAMP signaling alterations in adrenal Cushing project), the Conny-Maeva Charitable Foundation, the Brou de Lauriere Fondation, and the Intramural Program of the Eunice Kennedy Shriver, National Institute of Child Health & Human Development (Z01 HD008920-04). NR 40 TC 12 Z9 13 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2015 VL 100 IS 6 BP E926 EP E935 DI 10.1210/jc.2014-4204 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ8ET UT WOS:000360840000013 PM 25853793 ER PT J AU Zilbermint, M Xekouki, P Faucz, FR Berthon, A Gkourogianni, A Schernthaner-Reiter, MH Batsis, M Sinaii, N Quezado, MM Merino, M Merino, M Abraham, SB Libe, R Assie, G Espiard, S Drougat, L Ragazzon, B Davis, A Gebreab, SY Neff, R Kebebew, E Bertherat, J Lodish, MB Stratakis, CA AF Zilbermint, Mihail Xekouki, Paraskevi Faucz, Fabio R. Berthon, Annabel Gkourogianni, Alexandra Schernthaner-Reiter, Marie Helene Batsis, Maria Sinaii, Ninet Quezado, Martha M. Merino, Maria Hodes, Aaron Abraham, Smita B. Libe, Rossella Assie, Guillaume Espiard, Stephanie Drougat, Ludivine Ragazzon, Bruno Davis, Adam Gebreab, Samson Y. Neff, Ryan Kebebew, Electron Bertherat, Jerome Lodish, Maya B. Stratakis, Constantine A. TI Primary Aldosteronism and ARMC5 Variants SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MACRONODULAR ADRENAL-HYPERPLASIA; HYPERALDOSTERONISM TYPE-II; PRECLINICAL CUSHINGS-SYNDROME; KCNJ5 MUTATIONS; SOMATIC MUTATIONS; CHANNEL MUTATIONS; BLOOD-PRESSURE; CONNS-SYNDROME; HYPERTENSION; CORTISOL AB Context: Primary aldosteronism is one of the leading causes of secondary hypertension, causing significant morbidity and mortality. A number of genetic defects have recently been identified in primary aldosteronism, whereas we identified mutations in ARMC5, a tumor-suppressor gene, in cortisol-producing primary macronodular adrenal hyperplasia. Objective: We investigated a cohort of 56 patients who were referred to the National Institutes of Health for evaluation of primary aldosteronism for ARMC5 defects. Methods: Patients underwent step-wise diagnosis, with measurement of serum aldosterone and plasma renin activity followed by imaging, saline suppression and/or oral salt loading tests, plus adrenal venous sampling. Cortisol secretion was also evaluated; unilateral or bilateral adrenalectomy was performed, if indicated. DNA, protein, and transfection studies in H295R cells were conducted by standard methods. Results: We identified 12 germline ARMC5 genetic alterations in 20 unrelated and two related individuals in our cohort (39.3%). ARMC5 sequence changes in 6 patients (10.7%) were predicted to be damaging by in silico analysis. All affected patients carrying a variant predicted to be damaging were African Americans (P = .0023). Conclusions: Germline ARMC5 variants may be associated with primary aldosteronism. Additional cohorts of patients with primary aldosteronism and metabolic syndrome, particularly African Americans, should be screened for ARMC5 sequence variants because these may underlie part of the known increased predisposition of African Americans to low renin hypertension. C1 [Zilbermint, Mihail; Xekouki, Paraskevi; Faucz, Fabio R.; Berthon, Annabel; Gkourogianni, Alexandra; Schernthaner-Reiter, Marie Helene; Batsis, Maria; Abraham, Smita B.; Espiard, Stephanie; Lodish, Maya B.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA. [Quezado, Martha M.; Merino, Maria] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hodes, Aaron] Rainbow Babies & Childrens Hosp, Univ Hosp Case Med Ctr, Dept Pediat, Cleveland, OH 44106 USA. [Libe, Rossella; Assie, Guillaume; Drougat, Ludivine; Ragazzon, Bruno] NHGRI, Cardiovasc Dis Sect, Genom Metab Cardiovasc & Inflammatory Dis Branch, NIH, Bethesda, MD 20892 USA. [Davis, Adam; Gebreab, Samson Y.; Neff, Ryan; Bertherat, Jerome] Inst Cochin Genet Mol, INSERM, Dept Endocrinol Metab & Diabet, Unit 1016,CNRS,UMR 8104, F-75014 Paris, France. [Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Ragazzon, Bruno/E-6541-2017; OI Ragazzon, Bruno/0000-0001-9476-4973; Schernthaner-Reiter, Marie Helene/0000-0002-7972-7610 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Clinical and Molecular Analysis of ACTH-Independent Steroid Hormone Production in Adrenocortical Tissue) [00-CH-0160]; Novartis Pharmaceuticals; Ipsen FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (protocol 00-CH-0160; Clinical and Molecular Analysis of ACTH-Independent Steroid Hormone Production in Adrenocortical Tissue). These organizations had no further role in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. The principal investigator had full access to all the data in the case and takes responsibility for the integrity of the data and the accuracy of the data interpretation.; DisclosureSummary: M.Z., P.X., F.R.F., A.G., A.B., M.H.S.-R., M.B., N.S., M.M.Q., M.M., A.H., S.B.A., R.L., G.A., S.E., L.D., B.R., A.D., S.Y.G., R.N., E.K., M.B.L., and C.A.S. have nothing to declare. J.B. received honoraria from Atterocor, grant support from Novartis Pharmaceuticals, and fees from Ipsen. NR 54 TC 18 Z9 18 U1 1 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2015 VL 100 IS 6 BP E900 EP E909 DI 10.1210/jc.2014-4167 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ8ET UT WOS:000360840000010 PM 25822102 ER PT J AU Nagaya, T Tanaka, N Kimura, T Kitabatake, H Fujimori, N Komatsu, M Horiuchi, A Yamaura, T Umemura, T Sano, K Gonzalez, FJ Aoyama, T Tanaka, E AF Nagaya, Tadanobu Tanaka, Naoki Kimura, Takefumi Kitabatake, Hiroyuki Fujimori, Naoyuki Komatsu, Michiharu Horiuchi, Akira Yamaura, Takahiro Umemura, Takeji Sano, Kenji Gonzalez, Frank J. Aoyama, Toshifumi Tanaka, Eiji TI Mechanism of the development of nonalcoholic steatohepatitis after pancreaticoduodenectomy SO BBA CLINICAL LA English DT Article DE NASH; Pancreaticoduodenectomy; Fatty acid; VLDL; MyD88 ID FATTY LIVER-DISEASE; CHOLINE-DEFICIENT DIET; PPAR-ALPHA; INSULIN-RESISTANCE; HEPATIC STEATOSIS; GENE-EXPRESSION; DOWN-REGULATION; METHIONINE; MICE; INFLAMMATION AB Background and aim: It is recognized that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), may develop after pancreaticoduodenectomy (PD). However, the mechanism of NASH development remains unclear. This study aimed to examine the changes in gene expression associated with NASH occurrence following PD. Methods: The expression of genes related to fatty acid/triglyceride (FA/TG) metabolism and inflammatory signaling was examined using liver samples obtained from 7 post-PD NASH patients and compared with 6 healthy individuals and 32 conventional NASH patients. Results: The livers of post-PD NASH patients demonstrated significant up-regulation of the genes encoding CD36, FA-binding proteins 1 and 4, acetyl-coenzyme A carboxylase alpha, diacylglycerol acyltransferase 2, and peroxisome proliferator-activated receptor (PPAR) gamma compared with normal and conventional NASH livers. Although serum apolipoprotein B (ApoB) and TG were decreased in post-PD NASH patients, the mRNAs of ApoB and microsomal TG transfer protein were robustly increased, indicating impaired TG export from the liver as very-low-density lipoprotein (VLDL). Additionally, elevated mRNA levels of myeloid differentiation primary response 88 and superoxide dismutases in post-PD NASH livers suggested significant activation of innate immune response and augmentation of oxidative stress generation. Conclusions: Enhanced FA uptake into hepatocytes and lipogenesis, up-regulation of PPAR gamma, and disruption of VLDL excretion into the circulation are possible mechanisms of steatogenesis after PD. General significance: These results provide a basis for understanding the pathogenesis of NAFLD/NASH following PD. (C) 2015 The Authors. 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/4.0/). C1 [Nagaya, Tadanobu; Tanaka, Naoki; Kimura, Takefumi; Kitabatake, Hiroyuki; Fujimori, Naoyuki; Komatsu, Michiharu; Umemura, Takeji; Tanaka, Eiji] Shinshu Univ, Sch Med, Dept Gastroenterol, Matsumoto, Nagano 3908621, Japan. [Tanaka, Naoki; Aoyama, Toshifumi] Shinshu Univ, Grad Sch Med, Dept Metab Regulat, Matsumoto, Nagano 3908621, Japan. [Horiuchi, Akira] Showa Inan Gen Hosp, Ctr Digest Dis, Komagane, Japan. [Yamaura, Takahiro] Iida Municipal Hosp, Dept Gastroenterol, Iida, Japan. [Sano, Kenji] Shinshu Univ Hosp, Dept Lab Med, Matsumoto, Nagano, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tanaka, N (reprint author), Shinshu Univ, Grad Sch Med, Dept Metab Regulat, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan. EM naopi@shinshu-u.ac.jp NR 33 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2214-6474 J9 BBA CLIN JI BBA Clin. PD JUN PY 2015 VL 3 BP 168 EP 174 DI 10.1016/j.bbacli.2015.02.001 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CR1ZB UT WOS:000361122900022 PM 26674248 ER PT J AU Fee, E Brown, TM AF Fee, Elizabeth Brown, Theodore M. TI A Return to the Social Justice Spirit of Alma-Ata SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID WORLD-HEALTH-ORGANIZATION; CARE C1 [Fee, Elizabeth] Natl Lib Med, NIH, Bethesda, MD 20894 USA. [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY USA. RP Fee, E (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM feee@mail.nih.gov NR 12 TC 0 Z9 0 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2015 VL 105 IS 6 BP 1096 EP 1097 DI 10.2105/AJPH.2015.302602 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CQ2XW UT WOS:000360466800021 PM 25880948 ER PT J AU Bush, A AF Bush, Andrew TI FOLLOW-UP AFTER PRETERM BIRTH/BPD SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract ID CHILDREN C1 [Bush, Andrew] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. [Bush, Andrew] Natl Heart & Lung Inst, Paediat Respirol, Bethesda, MD USA. [Bush, Andrew] Royal Brompton Harefield NHS Fdn Trust, London, England. EM a.bush@imperial.ac.uk FU National Institute for Health Research [NF-SI-0510-10192] NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD JUN PY 2015 VL 50 SU 39 BP S35 EP S36 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA CQ7NR UT WOS:000360791400039 ER PT J AU Bush, A AF Bush, Andrew TI LATE CONSEQUENCES OF CHILDHOOD ASTHMA SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract ID LUNG-FUNCTION C1 [Bush, Andrew] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. [Bush, Andrew] Natl Heart & Lung Inst, Bethesda, MD USA. [Bush, Andrew] Royal Brompton Harefield NHS Fdn Trust, London, England. EM a.bush@imperial.ac.uk FU Asthma UK [10/058]; National Institute for Health Research [NF-SI-0510-10192] NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD JUN PY 2015 VL 50 SU 39 BP S5 EP S6 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA CQ7NR UT WOS:000360791400007 ER PT J AU Bayefsky, M AF Bayefsky, M. TI Pre-implantation genetic diagnosis and the European convention on human rights: applying the 'consensus' and 'margin of appreciation' principles SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 31st Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) CY JUN 14-17, 2015 CL Lisbon, PORTUGAL SP European Soc Human Reprod & Embryol DE PGD; European convention on human rights; reproductive rights; margin of appreciation; consensus C1 [Bayefsky, M.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2015 VL 30 SU 1 MA P-391 BP 288 EP 288 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CP2XF UT WOS:000359740302057 ER PT J AU Lynch, CD Sundaram, R Maisog, JM Sweeney, AM Louis, GMB AF Lynch, C. D. Sundaram, R. Maisog, J. M. Sweeney, A. M. Louis, G. M. Buck TI Human reproduction keynote lecture - preconception stress increases the risk of infertility: results from a couple-based prospective cohort study, the LIFE study SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 31st Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) CY JUN 14-17, 2015 CL Lisbon, PORTUGAL SP European Soc Human Reprod & Embryol DE fecundity; infertility; stress C1 [Lynch, C. D.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Sundaram, R.; Maisog, J. M.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD USA. [Sweeney, A. M.] Texas A&M Hlth Sci Ctr, Dept Epidemiol & Biostat, College Stn, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2015 VL 30 SU 1 MA O-001 BP 1 EP 1 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CP2XF UT WOS:000359740300002 ER PT J AU Reigstad, MM Larsen, IK Myklebust, TA Robsahm, TE Oldereid, NB Brinton, LA Storeng, R AF Reigstad, M. M. Larsen, I. K. Myklebust, T. A. Robsahm, T. E. Oldereid, N. B. Brinton, L. A. Storeng, R. TI Risk of cancer in children born after assisted reproductive technology in Norway SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 31st Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) CY JUN 14-17, 2015 CL Lisbon, PORTUGAL SP European Soc Human Reprod & Embryol DE ART; IVF; leukemia; Hodgkin lymphoma; childhood cancer C1 [Reigstad, M. M.; Storeng, R.] Oslo Univ Hosp, Norwegian Natl Advisory Unit Womens Hlth, Women & Childrens Div, Rikshosp, Oslo, Norway. [Larsen, I. K.; Myklebust, T. A.; Robsahm, T. E.] Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway. [Oldereid, N. B.] Oslo Univ Hosp, Sect Reprod Med, Women & Childrens Div, Rikshosp, Oslo, Norway. [Brinton, L. A.] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2015 VL 30 SU 1 MA O-037 BP 17 EP 18 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CP2XF UT WOS:000359740300038 ER PT J AU Coutifaris, C Nulsen, J Cedars, M Eisenberg, E Zhang, H AF Coutifaris, C. Nulsen, J. Cedars, M. Eisenberg, E. Zhang, H. TI Effect of oxygen tension on embryo development and live birth in clinical in vitro fertilization (IVF) - the reproductive medicine network physiologic oxygen (PhOx) study SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 31st Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) CY JUN 14-17, 2015 CL Lisbon, PORTUGAL SP European Soc Human Reprod & Embryol DE IVF; oxygen tension; embryo development C1 [Coutifaris, C.] Univ Penn, Div Reprod Endocrinol & Infertil, Philadelphia, PA 19104 USA. [Nulsen, J.] Univ Connecticut, Div Reprod Endocrinol & Infertil, Hartford, CT 06112 USA. [Cedars, M.] Univ Calif San Francisco, Div Reprod Endocrinol & Infertil, San Francisco, CA 94143 USA. [Eisenberg, E.] NICHHD, Fertil & Infertil Branch, Bethesda, MD 20892 USA. [Zhang, H.] Yale Univ, Ctr Biostat Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2015 VL 30 SU 1 MA O-057 BP 25 EP 25 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CP2XF UT WOS:000359740300057 ER PT J AU Steiner, A Geisler, WM Eisenberg, E Diamond, M Legro, RS AF Steiner, A. Geisler, W. M. Eisenberg, E. Diamond, M. Legro, R. S. CA Reprod Med Network TI Chlamydia trachomatis serostatus is an independent predictor of pregnancy and pregnancy outcome SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 31st Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) CY JUN 14-17, 2015 CL Lisbon, PORTUGAL SP European Soc Human Reprod & Embryol DE Chlamydia; pregnancy prediction; ectopic C1 [Steiner, A.] Univ N Carolina, Obstet & Gynaecol, Chapel Hill, NC USA. [Geisler, W. M.] Univ Alabama Birmingham, Med, Birmingham, AL USA. [Eisenberg, E.] NICHD, NIH, Bethesda, MD USA. [Diamond, M.] Georgia Regents Univ, Obstet & Gynaecol, Augusta, GA USA. [Legro, R. S.] Penn State Univ, Obstet & Gynaecol, Hershey, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2015 VL 30 SU 1 MA O-065 BP 28 EP 29 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CP2XF UT WOS:000359740300065 ER PT J AU Moran, JJ Dranchak, P Srinivasan, R Guha, R Martinez, N MacArthur, R Inglese, J Svaren, J AF Moran, J. J. Dranchak, P. Srinivasan, R. Guha, R. Martinez, N. MacArthur, R. Inglese, J. Svaren, J. TI GENOME EDITING-ENABLED DRUG SCREENING ASSAYS IDENTIFY NOVEL PATHWAYS FOR TREATMENT OF CHARCOT-MARIE-TOOTH DISEASE SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Biennial Meeting of the Peripheral-Nerve-Society CY JUN 27-JUL 02, 2015 CL Quebec, CANADA SP Peripheral Nerve Soc C1 [Moran, J. J.; Srinivasan, R.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. [Svaren, J.] Univ Wisconsin, Dept Comparat Biosci, Madison, WI 53706 USA. [Dranchak, P.; Guha, R.; Martinez, N.; MacArthur, R.; Inglese, J.] Natl Ctr Adv Translat Sci, Bethesda, MD USA. [Inglese, J.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1085-9489 EI 1529-8027 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD JUN PY 2015 VL 20 IS 2 BP 194 EP 194 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CP9LC UT WOS:000360214600278 ER PT J AU Blau, JE Collins, MT AF Blau, Jenny E. Collins, Michael T. TI The PTH-Vitamin D-FGF23 axis SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Review DE Fibroblast growth factor 23 (FGF23); Parathyroid Hormone (PTH); Vitamin D; Phosphate; Hypophosphatemic rickets; Chronic Renal Failure; 1-alpha hydroxylase ID FIBROBLAST-GROWTH-FACTOR; CHRONIC KIDNEY-DISEASE; X-LINKED HYPOPHOSPHATEMIA; TUMOR-INDUCED OSTEOMALACIA; RENAL PHOSPHATE-TRANSPORT; AUTOSOMAL RECESSIVE HYPOPHOSPHATEMIA; LEFT-VENTRICULAR HYPERTROPHY; 23 IN-VIVO; PARATHYROID-HORMONE; PRIMARY HYPERPARATHYROIDISM AB Fibroblast growth factor 23 (FGF23) has emerged as an important regulator of phosphate and vitamin D homeostasis. It is important to understand how FGF23 interacts with vitamin D and parathyroid hormone (PTH) in a FGF23-Vitamin D-PTH axis to regulate mineral homeostasis. In this review, we discuss the genomic structure, and transcriptional, translational, and posttranslational regulation of FGF23. We describe its interaction with PTH and vitamin D, disorders of altered FGF23 states, and emerging therapies for diseases of FGF23 based upon these findings. This discussion helps redefine the role of PTH and vitamin D in relation to a complex bone-kidney-parathyroid loop, and points to areas within this complicated field in need of further clarification and research. C1 [Blau, Jenny E.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Collins, Michael T.] NIDCR, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Collins, MT (reprint author), NIDCR, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. EM mc247k@nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services FX This research was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 96 TC 6 Z9 7 U1 3 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 EI 1573-2606 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD JUN PY 2015 VL 16 IS 2 BP 165 EP 174 DI 10.1007/s11154-015-9318-z PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ1XK UT WOS:000360393400010 PM 26296372 ER PT J AU Lai, H Gereau, RW Luo, Y O'Donnell, M Rudick, CN Pontari, M Mullins, C Klumpp, DJ AF Lai, Henry Gereau, Robert W. Luo, Yi O'Donnell, Michael Rudick, Charles N. Pontari, Michel Mullins, Chris Klumpp, David J. TI Animal Models of Urologic Chronic Pelvic Pain Syndromes: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network SO UROLOGY LA English DT Article ID CYSTITIS/PAINFUL BLADDER SYNDROME; URINARY-TRACT-INFECTION; INTERSTITIAL CYSTITIS; HYPERSENSITIVITY; INFLAMMATION; DISTENSION; ACTIVATION; STRESS; RATS; MICE AB OBJECTIVE To describe the approach taken by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network investigators to advance the utility of urologic chronic pelvic pain syndromes (UCPPS) animal models. METHODS A multidisciplinary team of investigators representing basic science and clinical expertise defined key phenotypic criteria for rodent models of UCPPS. UCPPS symptoms were prioritized based on their clinical significance. Methods for quantifying animal correlates to patient symptoms were developed. The methods were implemented across proposed rodent models for evaluation and comparison of animals for phenotypic characteristics relevant to human symptomatology. RESULTS Pelvic pain and urinary frequency were deemed primary features of human UCPPS and were prioritized for assessment in animals. Nociception was quantified using visceromotor response to bladder distention and by applying von Frey filaments to the lower abdomen (referred tactile allodynia). Micturition activity was assessed as free voiding using micturition cages or blotting pad assays and in response to bladder filling by cystometry. Models varied in both depth of characterization and degree of recapitulating pelvic pain and urinary frequency characteristics of UCPPS. CONCLUSION Rodent models that reflect multiple key characteristics of human UCPPS may be identified and provide enhanced clinical significance to mechanistic studies. We have developed a strategy for evaluating current and future animal models of UCPPS based on human symptomatology. This approach provides a foundation for improved translation between mechanistic studies in animals and clinical research and serves as a validation strategy for assessing validity of models for symptom-driven disorders of unknown etiology. (C) 2015 Elsevier Inc. C1 [Lai, Henry] Washington Univ, Div Urol Surg, Dept Surg, Sch Med, St Louis, MO 63110 USA. Washington Univ, Dept Anesthesiol, Sch Med, St Louis, MO 63110 USA. Univ Iowa, Dept Urol, Carver Coll Med, Iowa City, IA 52242 USA. Northwestern Univ, Dept Urol, Feinberg Sch Med, Chicago, IL 60611 USA. Temple Univ, Dept Urol, Sch Med, Philadelphia, PA 19122 USA. NIDDK, Div Kidney Urol & Hematol Dis KUH, NIH, Bethesda, MD USA. RP Lai, H (reprint author), Washington Univ, Div Urol Surg, Dept Surg, Sch Med, 4960 Childrens Pl,Campus 8242, St Louis, MO 63110 USA. EM laih@wudosis.wustl.edu OI Gereau, Robert/0000-0002-5428-4251 FU National Institute of Diabetes and Digestive Kidney Diseases MAPP Research Network [DK-082315, DK-094964, DK-082344, DK-082342] FX Financial support was given by the National Institute of Diabetes and Digestive Kidney Diseases MAPP Research Network, grants: DK-082315 (H. Henry Lai, Robert W. Gereau), DK-094964 (H. Henry Lai), DK-082344 (Yi Luo, Michael O'Donnell), DK-082342 (David J. Klumpp). Michel Pontari is a consultant to Eli Lilly Company. The remaining authors declare that they have no relevant financial interests. NR 30 TC 3 Z9 3 U1 0 U2 0 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 JUN PY 2015 VL 85 IS 6 BP 1454 EP 1465 DI 10.1016/j.urology.2015.03.007 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA CP8QJ UT WOS:000360158900066 PM 26099889 ER PT J AU Yang, RF Tsai-Morris, CH Kang, JH Dufau, ML AF Yang, Ruifeng Tsai-Morris, Chon-Hwa Kang, Jung Hoon Dufau, Maria L. TI Elucidation of RNA binding regions of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) to transcripts of a chromatin remodeling protein essential for spermatogenesis SO HORMONE MOLECULAR BIOLOGY AND CLINICAL INVESTIGATION LA English DT Article DE electrophoretic mobility gel shift assays (EMSA); gonadotropin-regulated testicular RNA helicase (GRTH); RNA-protein interaction; spermatogenesis; transition protein 2 (Tp2) ID 3 UNTRANSLATED REGION; PROTAMINE-2 MESSENGER-RNA; TRANSITION PROTEIN-2; GERM-CELLS; TRANSLATION; SEQUENCES; HORMONE; TESTIS; MSY2; MICE AB Background: Gonadotropin-regulated testicular RNA helicase (GRTH) is a testis-specific member of the DEAD-box family of RNA helicases present in Leydig and germ cells. It is a transport protein of mRNAs from nucleus to cytoplasmic sites and is essential for posttranscriptional regulation and completion of spermatogenesis. Transition protein 2 (Tp2), which associates with GRTH and is required for spermatid elongation, failed to express in GRTH null mice with impaired mRNA nuclear export. The present study determines GRTH binding motifs/regions that associate with Tp2 mRNA transcripts. Materials and methods: RNA-protein interaction was analyzed using biotin-labeled electrophoretic mobility gel shift assays (EMSA). 3'-biotin-labeled RNA (Tp2) was incubated with mGRTH protein (full length/sequential deletion of specific and conserved RNA helicase motifs of GRTH) expressed from in vitro TNT coupled reticulocyte lysate system. Binding specificity was further elucidated by mutagenesis and antibody supershift analysis. Results: RNA-EMSA revealed that the 3' UTR of Tp2 RNA (127 nt from TGA) was retarded in presence of full length GRTH. Nucleotide sequences downstream of TGA of the Tp2 transcript (1-47 and 78-127 nt) are important for binding to GRTH. Sequential deletions/point mutations in GRTH revealed region(s) of conserved binding motifs of RNA helicases (Ia and V) essential for GRTH binding to Tp2 mRNA. Conclusions: Our studies provide insights into the association of Tp2 expression via binding to the conserved RNA binding motifs of GRTH protein and the basis for understanding GRTH in the regulation of the genes essential for germ cell elongation and completion of spermatogenesis. C1 [Yang, Ruifeng; Tsai-Morris, Chon-Hwa; Kang, Jung Hoon; Dufau, Maria L.] NICHHD, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NICHD,NIH, Bethesda, MD 20892 USA. RP Tsai-Morris, CH (reprint author), NICHHD, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NICHD,NIH, Bethesda, MD 20892 USA. EM morrisch@mail.nih.gov FU Intramural NIH HHS NR 21 TC 0 Z9 0 U1 2 U2 5 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1868-1883 EI 1868-1891 J9 HORM MOL BIOL CLIN I JI Horm. Mol. Biol. Clin. Investig. PD JUN PY 2015 VL 22 IS 3 BP 119 EP 130 DI 10.1515/hmbci-2015-0004 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CQ2UC UT WOS:000360456100003 PM 25910401 ER PT J AU Weinberg, CR Shi, M DeRoo, LA Basso, O Skjaerven, R AF Weinberg, Clarice R. Shi, Min DeRoo, Lisa A. Basso, Olga Skjaerven, Rolv TI Season and preterm birth in Norway: A cautionary tale SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Preterm birth; seasonality; harmonic analysis ID AGE AB Background: Preterm birth is a common, costly and dangerous pregnancy complication. Seasonality of risk would suggest modifiable causes. Methods: We examine seasonal effects on preterm birth, using data from the Medical Birth Registry of Norway (2 321 652 births), and show that results based on births are misleading and a fetuses-at-risk approach is essential. In our harmonic-regression Cox proportional hazards model we consider fetal risk of birth between 22 and 37 completed weeks of gestation. We examine effects of both day of year of conception (for early effects) and day of ongoing gestation (for seasonal effects on labour onset) as modifiers of gestational-age-based risk. Results: Naive analysis of preterm rates across days of birth shows compelling evidence for seasonality (P< 10(-152)). However, the reconstructed numbers of conceptions also vary with season (P< 10(-307)), confounding results by inducing seasonal variation in the age distribution of the fetal population at risk. When we instead properly treat fetuses as the individuals at risk, restrict analysis to pregnancies with relatively accurate ultrasound-based assessment of gestational age (available since 1998) and adjust for socio-demographic factors and maternal smoking, we find modest effects of both time of year of conception and time of year at risk, with peaks for early preterm near early January and early July. Conclusions: Analyses of seasonal effects on preterm birth are demonstrably vulnerable to confounding by seasonality of conception, measurement error in conception dating, and socio-demographic factors. The seasonal variation based on fetuses reveals two peaks for early preterm, coinciding with New Year's Day and the early July beginning of Norway's summer break, and may simply reflect a holiday-related pattern of unintended conception. C1 [Weinberg, Clarice R.; Shi, Min] NIEHS, Res Triangle Pk, NC 27709 USA. [DeRoo, Lisa A.; Skjaerven, Rolv] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. [DeRoo, Lisa A.; Skjaerven, Rolv] Med Birth Registry Norway, Bergen, Norway. [Basso, Olga] McGill Univ, Dept Obstet & Gynecol, Montreal, PQ H3A 2T5, Canada. [Basso, Olga] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. RP Weinberg, CR (reprint author), NIEHS, MD A3-03,111 T-W Alexander Dr, Res Triangle Pk, NC 27709 USA. EM weinber2@niehs.nih.gov RI Basso, Olga/E-5384-2010 OI Basso, Olga/0000-0001-9298-4921 FU Norwegian Research Council; National Institute of Environmental Health Sciences [Z01 AES 040006-18]; Intramural Research Program of the NIH FX This research was supported by the Norwegian Research Council and in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, under project Z01 AES 040006-18. NR 15 TC 1 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 2015 VL 44 IS 3 BP 1068 EP 1078 DI 10.1093/ije/dyv100 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CP2JB UT WOS:000359702200041 PM 26045507 ER PT J AU Furey, ML Drevets, WC Szczepanik, J Khanna, A Nugent, A Zarate, CA AF Furey, Maura L. Drevets, Wayne C. Szczepanik, Joanna Khanna, Ashish Nugent, Allison Zarate, Carlos A., Jr. TI Pretreatment Differences in BOLD Response to Emotional Faces Correlate with Antidepressant Response to Scopolamine SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Biomarker; antimuscarinic; mood disorders; anticholinergic ID MAJOR DEPRESSIVE DISORDER; MEDIAL PREFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; SUBGENUAL CINGULATE; VISUAL ACTIVATION; NEURAL RESPONSE; WORKING-MEMORY; MOOD-STATE; BIAS; FMRI AB Background: Faster acting antidepressants and biomarkers that predict treatment response are needed to facilitate the development of more effective treatments for patients with major depressive disorders. Here, we evaluate implicitly and explicitly processed emotional faces using neuroimaging to identify potential biomarkers of treatment response to the antimuscarinic, scopolamine. Methods: Healthy participants (n = 15) and unmedicated-depressed major depressive disorder patients (n = 16) participated in a double-blind, placebo-controlled crossover infusion study using scopolamine (4 mu g/kg). Before and following scopolamine, blood oxygen-level dependent signal was measured using functional MRI during a selective attention task. Two stimuli comprised of superimposed pictures of faces and houses were presented. Participants attended to one stimulus component and performed a matching task. Face emotion was modulated (happy/sad) creating implicit (attend-houses) and explicit (attend-faces) emotion processing conditions. The pretreatment difference in blood oxygen-level dependent response to happy and sad faces under implicit and explicit conditions (emotion processing biases) within a-priori regions of interest was correlated with subsequent treatment response in major depressive disorder. Results: Correlations were observed exclusively during implicit emotion processing in the regions of interest, which included the subgenual anterior cingulate (P < .02) and middle occipital cortices (P < .02). Conclusions: The magnitude and direction of differential blood oxygen-level- dependent response to implicitly processed emotional faces prior to treatment reflect the potential to respond to scopolamine. These findings replicate earlier results, highlighting the potential for pretreatment neural activity in the middle occipital cortices and subgenual anterior cingulate to inform us about the potential to respond clinically to scopolamine. C1 [Furey, Maura L.; Szczepanik, Joanna; Nugent, Allison; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Drevets, Wayne C.] Janssen Pharmaceut LLC, Titusville, NJ USA. [Khanna, Ashish] Brooklyn Hosp Ctr, Jewish Med Ctr, Phys Med & Rehabil, Brooklyn, NY USA. RP Furey, ML (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, 10 Ctr Dr,MSC 1282,10CRC,Room 7-3345, Bethesda, MD 20892 USA. EM mfurey@mail.nih.gov OI Nugent, Allison/0000-0003-2569-2480 FU NIH NIMH-DIRP FX We thank Michele Drevets and Joan Williams for patient recruitment and evaluation and the 5SW Day Hospital nursing staff for medical support. This research was supported by the NIH NIMH-DIRP. NR 65 TC 2 Z9 2 U1 4 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2015 VL 18 IS 8 DI 10.1093/ijnp/pyv028 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CP2JO UT WOS:000359703500012 ER PT J AU Yingst, SL Facemire, P Chuvala, L Norwood, D Wolcott, M Huzella, L AF Yingst, Samuel L. Facemire, Paul Chuvala, Lara Norwood, David Wolcott, Mark Huzella, Louis TI Pathological findings and diagnostic implications of a rhesus macaque (Macacca mulatta) model of aerosol exposure to Burkholderia mallei (glanders) SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID PSEUDOMALLEI; IDENTIFICATION; MOUSE; MICE; PCR AB Burkholderia mallei is a Gram-negative bacillus that causes a pneumonic disease known as glanders in equids and humans, and a lymphatic infection known as farcy, primarily in equids. With the potential to infect humans by the respiratory route, aerosol exposure can result in severe, occasionally fatal, pneumonia. Today, glanders infections in humans are rare, likely due to less frequent contact with infected equids than in the past. Acutely ill humans often have non-specific clinical signs and in order to diagnose cases, especially in scenarios of multiple cases in an unexpected setting, rapid diagnostics for B. mallei may be critical. The pathogenesis of acute glanders in the rhesus macaque (Macaca mulatta) was studied as an initial effort to improve diagnostic methods. In the study described here, the diagnostic techniques of PCR, culture and histopathology were compared. The results indicated that PCR may provide rapid, non-invasive diagnosis of glanders in some cases. As expected, PCR results were positive in lung tissue in 11/12 acutely infected rhesus macaques, but more importantly in terms of diagnostic algorithm development, PCR results were frequently positive in non-invasive samples such as broncho-alveolar lavage or nasal swabs (7/12) and occasionally in blood (3/12). However, conventional bacterial culture failed to recover bacteria in many of these samples. The study showed that the clinical presentation of aerosol-exposed rhesus macaques is similar to descriptions of human glanders and that PCR has potential for rapid diagnosis of outbreaks, if not individual cases. C1 [Chuvala, Lara] Ordway Res Inst, Albany, NY USA. [Huzella, Louis] NIAID, Integrated Res Facil, Div Clin Res, NIH, Frederick, MD USA. EM paul.r.facemire2.mil@mail.mil NR 22 TC 0 Z9 0 U1 0 U2 4 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 JUN PY 2015 VL 64 BP 646 EP 653 DI 10.1099/jmm.0.000065 PN 6 PG 8 WC Microbiology SC Microbiology GA CP1CR UT WOS:000359614000010 PM 25850696 ER PT J AU Wan, WZ Liu, Q Lionakis, MS Marino, APMP Anderson, SA Swamydas, M Murphy, PM AF Wan, Wuzhou Liu, Qian Lionakis, Michail S. Marino, Ana Paula M. P. Anderson, Stasia A. Swamydas, Muthulekha Murphy, Philip M. TI Atypical chemokine receptor 1 deficiency reduces atherogenesis in ApoE-knockout mice SO CARDIOVASCULAR RESEARCH LA English DT Article DE Atherosclerosis; Inflammation; Leukocytes; Chemokine receptor ID DUFFY ANTIGEN RECEPTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; GENETIC DELETION; ATHEROSCLEROSIS; DARC; IMMUNE; POLYMORPHISM; MECHANISMS; CELLS AB Aims Atypical chemokine receptor 1 (Ackr1; previously known as the Duffy antigen receptor for chemokines or Darc) is thought to regulate acute inflammatory responses in part by scavenging inflammatory CC and CXC chemokines; however, evidence for a role in chronic inflammation has been lacking. Here we investigated the role of Ackr1 in chronic inflammation, in particular in the setting of atherogenesis, using the apolipoprotein E-deficient (ApoE(-/-)) mouse model. Methods and results Ackr1(-/-) ApoE(-/-) and Ackr1(+/+) ApoE(-/-) littermates were obtained by crossing ApoE(-/-) mice and Ackr1(-/-) mice on a C57BL/6J background. Ackr1(+/+) ApoE(-/-) mice fed a Western diet up-regulated Ackr1 expression in the aorta and had markedly increased atherosclerotic lesion size compared with Ackr1(-/-) ApoE(-/-) mice. This difference was observed in both the whole aorta and the aortic root in both early and late stages of the model. Ackr1 deficiency did not affect serum cholesterol levels or macrophage, collagen or smooth muscle cell content in atherosclerotic plaques, but significantly reduced the expression of Ccl2 and Cxcl1 in the whole aorta of ApoE(-/-) mice. In addition, Ackr1 deficiency resulted in a modest decrease in T cell subset frequency and inflammatory mononuclear phagocyte content in aorta and blood in the model. Conclusions Ackr1 deficiency appears to be protective in the ApoE knockout model of atherogenesis, but it is associated with only modest changes in cytokine and chemokine expression as well as T-cell subset frequency and inflammatory macrophage content. C1 [Wan, Wuzhou; Liu, Qian; Marino, Ana Paula M. P.; Murphy, Philip M.] NIAID, Mol Signaling Sect, LMI, NIH, Bethesda, MD 20892 USA. [Lionakis, Michail S.; Swamydas, Muthulekha] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Anderson, Stasia A.] NHLBI, Anim MRI Core, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, LMI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pmm@nih.gov FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. NR 29 TC 1 Z9 1 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 EI 1755-3245 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUN 1 PY 2015 VL 106 IS 3 BP 478 EP 487 DI 10.1093/cvr/cvv124 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO3VG UT WOS:000359088400015 PM 25858253 ER PT J AU Panchenko, AR Babu, MM AF Panchenko, Anna R. Babu, M. Madan TI Editorial overview: Linking protein sequence and structural changes to function in the era of next-generation sequencing SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Editorial Material C1 [Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Babu, M. Madan] MRC Lab Mol Biol, Cambridge CB2 OQH, England. RP Panchenko, AR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM panch@ncbi.nlm.nih.gov; madanm@mrc-Imb.cam.ac.uk FU Medical Research Council [MC_U105185859] NR 0 TC 1 Z9 1 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X EI 1879-033X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 2015 VL 32 BP VIII EP X DI 10.1016/j.sbi.2015.06.005 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CO3BT UT WOS:000359032300002 PM 26199202 ER PT J AU Nussinov, R Tsai, CJ AF Nussinov, Ruth Tsai, Chung-Jung TI 'Latent drivers' expand the cancer mutational landscape SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID FREE-ENERGY LANDSCAPE; MISSENSE MUTATIONS; SOMATIC MUTATIONS; KINASE DOMAIN; EGFR KINASE; ONCOGENIC ACTIVATION; MYELOID-LEUKEMIA; TYROSINE KINASES; PROTEIN-KINASES; NEXT-GENERATION AB A major challenge facing the community involves identification of mutations that drive cancer. Analyses of cancer genomes to detect, and distinguish, 'driver' from 'passenger' mutations are daunting tasks. Here we suggest that there is a third 'latent driver' category. 'Latent driver' mutations behave as passengers, and do not confer a cancer hallmark. However, coupled with other emerging mutations, they drive cancer development and drug resistance. 'Latent drivers' emerge prior to and during cancer evolution. These allosteric mutations can work through 'AND' all-or-none or incremental 'Graded' logic gate mechanisms. Current diagnostic platforms generally assume that actionable 'driver' mutations are those appearing most frequently in cancer. We propose that 'latent driver' detection may help forecast cancer progression and modify personalized drug regimes. C1 [Nussinov, Ruth; Tsai, Chung-Jung] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM NussinoR@helix.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 64 TC 7 Z9 7 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X EI 1879-033X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 2015 VL 32 BP 25 EP 32 DI 10.1016/j.sbi.2015.01.004 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CO3BT UT WOS:000359032300006 PM 25661093 ER PT J AU Shaytan, AK Landsman, D Panchenko, AR AF Shaytan, Alexey K. Landsman, David Panchenko, Anna R. TI Nucleosome adaptability conferred by sequence and structural variations in histone H2A-H2B dimers SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID REGULATES CHROMATIN COMPACTION; RNA-POLYMERASE-II; FUNCTIONAL-PROPERTIES; CRYSTAL-STRUCTURE; CORE PARTICLE; VARIANT TH2B; X-CHROMOSOME; H2A VARIANTS; DNA; H2A.BBD AB Nucleosome variability is essential for their functions in compacting the chromatin structure and regulation of transcription, replication and cell reprogramming. The DNA molecule in nucleosomes is wrapped around an octamer composed of four types of core histones (H3, H4, H2A, H2B). Nucleosomes represent dynamic entities and may change their conformation, stability and binding properties by employing different sets of histone variants or by becoming post-translationally modified. There are many variants of histones H2A and H2B. Specific H2A and H2B variants may preferentially associate with each other resulting in different combinations of variants and leading to the increased combinatorial complexity of nucleosomes. In addition, the H2A H2B dimer can be recognized and substituted by chaperones/remodelers as a distinct unit, can assemble independently and is stable during nucleosome unwinding. In this review we discuss how sequence and structural variations in H2A H2B dimers may provide necessary complexity and confer the nucleosome functional variability. C1 [Shaytan, Alexey K.; Landsman, David; Panchenko, Anna R.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Panchenko, AR (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM panch@ncbi.nlm.nih.gov RI Shaytan, Alexey/D-7306-2012; OI Shaytan, Alexey/0000-0003-0312-938X; Landsman, David/0000-0002-9819-6675 FU Intramural Research Program of the National Library of Medicine NIH; US-Russia Collaboration in the Biomedical Sciences NIH visiting fellows program FX We would like to thank Victor Zhurkin, Paul Talbert and Vasily Studitsky for inspiring discussions and comments. This work was supported by the Intramural Research Program of the National Library of Medicine NIH. AS is supported by the US-Russia Collaboration in the Biomedical Sciences NIH visiting fellows program. NR 74 TC 12 Z9 13 U1 1 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X EI 1879-033X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 2015 VL 32 BP 48 EP 57 DI 10.1016/j.sbi.2015.02.004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CO3BT UT WOS:000359032300009 PM 25731851 ER PT J AU Andrade, LR AF Andrade, Leonardo R. TI Evidence for changes in beta- and gamma-actin proportions during inner ear hair cell life SO CYTOSKELETON LA English DT Article DE beta-actin; gamma-actin; hair cells; stereocilia; immunogold TEM ID HEARING-LOSS; MOLECULAR TREADMILL; ACTG1 MUTATIONS; IN-VIVO; STEREOCILIA; PROTEINS; PROTOCADHERIN-15; OVEREXPRESSION; LOCALIZATION; CYTOSKELETAL AB Cytoplasmic actin isoforms beta (-) and gamma (-) perform crucial physiological roles in inner ear hair cells (HC). The stereocilium, which is structured by parallel actin filaments composed of both isoforms, is the responsive organelle to mechanical stimuli such as sound, gravity and head movements. Modifications in isoform proportions affect the function of the stereocilia as previously shown in genetic studies of mutant mice. Here, immunogold labeling TEM studies in mice showed that both - and -actin isoforms colocalize throughout stereocilia actin filaments, adherens junctions and cuticular plates as early as embryonic stage 16.5. Gold-particle quantification indicated that there was 40% more - actin than -actin at E16.5. In contrast, - and -actin were equally concentrated in adult stereocilia of cochlear and vestibular HC. Interestingly, all actin-based structures presented almost five-fold more -actin than -actin in 22 month- old mice, suggesting that -actin is probably under-expressed during the aging process. These data provide evidence of dynamic modifications of the actin isoforms in stereocilia, cuticular plates and cell junctions during the whole HC life. (c) 2015 Wiley Periodicals, Inc. C1 [Andrade, Leonardo R.] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA. [Andrade, Leonardo R.] Univ Fed Rio de Janeiro, Inst Biomed Sci, Lab Biomineralizat, BR-21941902 Rio de Janeiro, RJ, Brazil. RP Andrade, LR (reprint author), Univ Fed Rio de Janeiro, CCS, ICB, Av Carlos Chagas Filho 373,F2-30, BR-21941902 Rio de Janeiro, RJ, Brazil. EM andrade@histo.ufrj.br FU Intramural NIH HHS [Z01 DC000002-20] NR 34 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1949-3584 EI 1949-3592 J9 CYTOSKELETON JI Cytoskeleton PD JUN PY 2015 VL 72 IS 6 BP 282 EP 291 DI 10.1002/cm.21227 PG 10 WC Cell Biology SC Cell Biology GA CO8MQ UT WOS:000359423900003 PM 26033950 ER PT J AU Mehta, A Zhang, L Boufraqech, M Zhang, YQ Patel, D Shen, M Kebebew, E AF Mehta, Amit Zhang, Lisa Boufraqech, Myriem Zhang, Yaqin Patel, Dhaval Shen, Min Kebebew, Electron TI Carfilzomib is an effective anticancer agent in anaplastic thyroid cancer SO ENDOCRINE-RELATED CANCER LA English DT Article DE anaplastic thyroid cancer; high-throughput screening; carfilzomib; proteasome inhibitor ID PROTEASOME INHIBITOR BORTEZOMIB; MESENCHYMAL TRANSITION; CARCINOMA-CELLS; PROSTATE-CANCER; BREAST-CANCER; APOPTOSIS; DRUGS; RESISTANCE; P27(KIP1); AUTOPHAGY AB Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies. Currently, there is no standard or effective therapy for ATC. Drug repurposing for cancer treatment is an emerging approach for identifying compounds that may have antineoplastic effects. The aim of this study was to use high-throughput drug library screening to identify and subsequently validate novel therapeutic agents with anticancer effects in ATC. We performed quantitative high-throughput screening (qHTS) in ATC cell lines (SW-1736, 8505C, and C-643), using a compound library of 3282 drugs. qHTS identified 100 compounds that were active in all three ATC cell lines. Proteasome inhibitors were one of the most active drug categories according to enrichment analysis. Of the three proteasome inhibitors screened, a second-generation proteasome inhibitor, carfilzomib, was the most active. Treatment of ATC cells with carfilzomib significantly inhibited cellular proliferation and induced G2/M cell cycle arrest and caspase-dependent apoptosis. Mechanistically, carfilzomib increased expression of p27 (CDKN1B) and decreased expression of the anti-apoptotic protein ATF4. Pretreatment with carfilzomib reduced in vivo metastases (lung, bone, liver, and kidney) and disease progression, and decreased N-cadherin expression. Carfilzomib treatment of mice with established, widely metastatic disease significantly increased their survival, without significant toxicity. Our findings support the use or clinical study of carfilzomib as a therapeutic option in patients with advanced and metastatic ATC. C1 [Mehta, Amit; Zhang, Lisa; Boufraqech, Myriem; Patel, Dhaval; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA. [Mehta, Amit] Geisel Sch Med Dartmouth, Hanover, NH 03755 USA. [Zhang, Yaqin; Shen, Min] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov RI Boufraqech, Myriem/E-4823-2016; OI Patel, Dhaval/0000-0002-5744-568X FU intramural research programs of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; National Institutes of Health (NIH) Medical Research Scholars Program; NIH FX This research was supported by the intramural research programs of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, as well as the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH, and generous contributions to the Foundation for the NIH from Pfizer, Inc., the Doris Duke Charitable Foundation, Alexandria Real Estate Equities, Inc., Mr and Mrs Joel S Marcus, and the Howard Hughes Medical Institute, as well as other private donors. For a complete list, please visit the Foundation website at: http://fnih.org/work/education-training-0/medical-research- scholars-program. NR 43 TC 7 Z9 7 U1 0 U2 10 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2015 VL 22 IS 3 BP 319 EP 329 DI 10.1530/ERC-14-0510 PG 11 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CO2RE UT WOS:000359003500015 PM 25972243 ER PT J AU Szarek, E Ball, ER Imperiale, A Tsokos, M Faucz, FR Giubellino, A Moussallieh, FM Namer, IJ Abu-Asab, MS Pacak, K Taieb, D Carney, JA Stratakis, CA AF Szarek, Eva Ball, Evan R. Imperiale, Alessio Tsokos, Maria Faucz, Fabio R. Giubellino, Alessio Moussallieh, Francois-Marie Namer, Izzie-Jacques Abu-Asab, Mones S. Pacak, Karel Taieb, David Carney, J. Aidan Stratakis, Constantine A. TI Carney triad, SDH-deficient tumors, and Sdhb(+/-) mice share abnormal mitochondria SO ENDOCRINE-RELATED CANCER LA English DT Article DE GIST; mitochondria; Carney triad; succinate dehydrogenase ID GASTROINTESTINAL STROMAL TUMORS; AUTONOMIC NERVE TUMORS; SUCCINATE-DEHYDROGENASE; MOLECULAR PATHOLOGY; INTERSTITIAL-CELLS; PDGFRA MUTATIONS; PARAGANGLIOMA; PROGNOSIS; MORPHOLOGY; GENE AB Carney triad (CTr) describes the association of paragangliomas (PGL), pulmonary chondromas, and gastrointestinal (GI) stromal tumors (GISTs) with a variety of other lesions, including pheochromocytomas and adrenocortical tumors. The gene(s) that cause CTr remain(s) unknown. PGL and GISTs may be caused by loss-of-function mutations in succinate dehydrogenase (SDH) (a condition known as Carney-Stratakis syndrome (CSS)). Mitochondrial structure and function are abnormal in tissues that carry SDH defects, but they have not been studied in CTr. For the present study, we examined mitochondrial structure in human tumors and GI tissue (GIT) of mice with SDH deficiency. Tissues from 16 CTr tumors (n=12), those with isolated GIST (n=1), and those with CSS caused by SDHC (n=1) and SDHD (n=2) mutations were studied by electron microscopy (EM). Samples of GIT from mice with a heterozygous deletion in Sdhb (Sdhb(+/-), n=4) were also studied by EM. CTr patients presented with mostly epithelioid GISTs that were characterized by plump cells containing a centrally located, round nucleus and prominent nucleoli; these changes were almost identical to those seen in the GISTs of patients with SDH. In tumor cells from patients, regardless of diagnosis or tumor type, cytoplasm contained an increased number of mitochondria with a 'hypoxic' phenotype: mitochondria were devoid of cristae, exhibited structural abnormalities, and were of variable size. Occasionally, mitochondria were small and round; rarely, they were thin and elongated with tubular cristae. Many mitochondria exhibited amorphous fluffy material with membranous whorls or cystic structures. A similar mitochondrial hypoxic phenotype was seen in Sdhb(+/-) mice. We concluded that tissues from SDH-deficient tumors, those from mouse GIT, and those from CTr tumors shared identical abnormalities in mitochondrial structure and other features. Thus, the still-elusive CTr defect(s) is(are) likely to affect mitochondrial function, just like germline SDH-deficiency does. C1 [Szarek, Eva; Faucz, Fabio R.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet SEGEN, Program Dev Endocrinol & Genet PDEGEN, NIH,CRC, Bethesda, MD 20892 USA. [Imperiale, Alessio; Moussallieh, Francois-Marie; Namer, Izzie-Jacques] Univ Hosp Strasbourg, Dept Biophys & Nucl Med, Strasbourg, France. [Imperiale, Alessio; Moussallieh, Francois-Marie; Namer, Izzie-Jacques] Univ Strasbourg, CNRS, Fac Med, Icube UMR 7357, Strasbourg, France. [Imperiale, Alessio; Moussallieh, Francois-Marie; Namer, Izzie-Jacques] FMTS, Strasbourg, France. [Tsokos, Maria] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Giubellino, Alessio] NICHD, SMN, PRAE, NIH, Bethesda, MD 20892 USA. [Abu-Asab, Mones S.] NEI, Sect Immunopathol & Lab Immunol, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Taieb, David] La Timone Univ Hosp, Dept Nucl Med, CERIMED, F-13385 Marseille 5, France. [Taieb, David] Inst J Paoli I Calmettes, INSERM, Marseille Cancerol Res Ctr, UMR1068, F-13009 Marseille, France. [Carney, J. Aidan] Mayo Clin, Emeritus Staff Ctr, Rochester, MN 55905 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet SEGEN, Program Dev Endocrinol & Genet PDEGEN, NIH,CRC, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA FX This investigation was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA. NR 55 TC 1 Z9 1 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2015 VL 22 IS 3 BP 345 EP 352 DI 10.1530/ERC-15-0069 PG 8 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CO2RE UT WOS:000359003500017 PM 25808178 ER PT J AU Beckers, A Lodish, MB Trivellin, G Rostomyan, L Lee, M Faucz, FR Yuan, B Choong, CS Caberg, JH Verrua, E Naves, LA Cheetham, TD Young, J Lysy, PA Petrossians, P Cotterill, A Shah, NS Metzger, D Castermans, E Ambrosio, MR Villa, C Strebkova, N Mazerkina, N Gaillard, S Barra, GB Casulari, LA Neggers, SJ Salvatori, R Jaffrain-Rea, ML Zacharin, M Santamaria, BL Zacharieva, S Lim, EM Mantovani, G Zatelli, MC Collins, MT Bonneville, JF Quezado, M Chittiboina, P Oldfield, EH Bours, V Liu, PF de Herder, WW Pellegata, N Lupski, JR Daly, AF Stratakis, CA AF Beckers, Albert Lodish, Maya Beth Trivellin, Giampaolo Rostomyan, Liliya Lee, Misu Faucz, Fabio R. Yuan, Bo Choong, Catherine S. Caberg, Jean-Hubert Verrua, Elisa Naves, Luciana Ansaneli Cheetham, Tim D. Young, Jacques Lysy, Philippe A. Petrossians, Patrick Cotterill, Andrew Shah, Nalini Samir Metzger, Daniel Castermans, Emilie Ambrosio, Maria Rosaria Villa, Chiara Strebkova, Natalia Mazerkina, Nadia Gaillard, Stephan Barra, Gustavo Barcelos Casulari, Luis Augusto Neggers, Sebastian J. Salvatori, Roberto Jaffrain-Rea, Marie-Lise Zacharin, Margaret Lecumberri Santamaria, Beatriz Zacharieva, Sabina Lim, Ee Mun Mantovani, Giovanna Zatelli, Maria Chaira Collins, Michael T. Bonneville, Jean-Francois Quezado, Martha Chittiboina, Prashant Oldfield, Edward H. Bours, Vincent Liu, Pengfei de Herder, Wouter W. Pellegata, Natalia Lupski, James R. Daly, Adrian F. Stratakis, Constantine A. TI X-linked acrogigantism syndrome: clinical profile and therapeutic responses SO ENDOCRINE-RELATED CANCER LA English DT Article DE gigantism; X chromosome; pituitary adenoma; pediatric; X-LAG syndrome; GPR101; FIPA; duplication ID HORMONE-RELEASING-HORMONE; MCCUNE-ALBRIGHT SYNDROME; GROWTH-HORMONE; PITUITARY-ADENOMAS; TRANSGENIC MICE; IN-VITRO; INTERACTING PROTEIN; RECEPTOR ANTAGONIST; ECTOPIC SECRETION; GENE-EXPRESSION AB X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of > +3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. C1 [Beckers, Albert; Rostomyan, Liliya; Petrossians, Patrick; Villa, Chiara; Bonneville, Jean-Francois; Daly, Adrian F.] Univ Liege, Ctr Hosp Univ Liege, Dept Endocrinol, B-4000 Liege, Belgium. [Lodish, Maya Beth; Trivellin, Giampaolo; Faucz, Fabio R.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. [Lee, Misu; Pellegata, Natalia] Helmholtz Zentrum Munchen, Inst Pathol, Neuherberg, Germany. [Yuan, Bo; Liu, Pengfei] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Choong, Catherine S.] Princess Margaret Hosp Children, Dept Pediat Endocrinol & Diabet, Subiaco, WA, Australia. [Caberg, Jean-Hubert; Castermans, Emilie; Bours, Vincent] Univ Liege, Ctr Hosp Univ Liege, Dept Clin Genet, B-4000 Liege, Belgium. [Verrua, Elisa; Mantovani, Giovanna] Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Clin Sci & Community Hlth, Endocrinol & Diabetol Unit, Milan, Italy. [Naves, Luciana Ansaneli; Casulari, Luis Augusto] Univ Brasilia, Dept Endocrinol, Brasilia, DF, Brazil. [Cheetham, Tim D.] Newcastle Univ, Royal Victoria Infirm, Dept Paediat Endocrinol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Young, Jacques] Hop Bicetre, GHU Paris Sud, INSERM, U693, F-94270 Le Kremlin Bicetre, France. [Lysy, Philippe A.] Catholic Univ Louvain, Pediat Endocrinol Unit, B-1200 Brussels, Belgium. [Cotterill, Andrew] Univ Queensland, Mater Med Res Inst, Brisbane, Qld, Australia. [Shah, Nalini Samir] King Edward Mem Hosp, Dept Endocrinol, Bombay, Maharashtra, India. [Metzger, Daniel] BC Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC, Canada. [Ambrosio, Maria Rosaria; Zatelli, Maria Chaira] Univ Ferrara, Dept Med Sci, Endocrinol Sect, I-44100 Ferrara, Italy. [Villa, Chiara] Hop Foch, Serv Anat & Cytol Pathol, Suresnes, France. [Villa, Chiara] Univ Paris 05, Hop Cochin, Inst Cochin, INSERM,U1016, Paris, France. [Strebkova, Natalia] Endocrinol Res Ctr, Inst Pediat Endocrinol, Moscow, Russia. [Mazerkina, Nadia] NN Burdenko Inst Neurosurg, Moscow, Russia. [Gaillard, Stephan] Hop Foch, Dept Neurosurg, Suresnes, France. [Barra, Gustavo Barcelos] Lab Sabin, Brasilia, DF, Brazil. [Neggers, Sebastian J.; de Herder, Wouter W.] Erasmus MC, Pituitary Ctr Rotterdam, Dept Med, Endocrinol Sect, Rotterdam, Netherlands. [Salvatori, Roberto] Johns Hopkins Univ, Dept Endocrinol, Baltimore, MD USA. [Jaffrain-Rea, Marie-Lise] Univ Aquila, Dept Endocrinol, IRCCS, I-67100 Laquila, Italy. [Jaffrain-Rea, Marie-Lise] Neuromed, Pozzilli, Italy. [Zacharin, Margaret] Royal Childrens Hosp, Dept Endocrinol & Diabet, Melbourne, Vic, Australia. [Lecumberri Santamaria, Beatriz] Hosp Univ La Paz, Dept Endocrinol, Madrid, Spain. [Zacharieva, Sabina] Med Univ Sofia, Clin Ctr Endocrinol & Gerontol, Sofia, Bulgaria. [Lim, Ee Mun] PathWest QEII Sir Charles Gairdner Hosp, Dept Clin Biochem Pharmacol & Toxicol, Nedlands, WA, Australia. [Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, NIH, Bethesda, MD USA. [Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Chittiboina, Prashant] NINDS, NIH, Bethesda, MD 20892 USA. [Oldfield, Edward H.] Univ Virginia, Sch Med, Dept Neurosurg, Charlottesville, VA 22908 USA. [Lupski, James R.] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Beckers, A (reprint author), Univ Liege, Ctr Hosp Univ Liege, Dept Endocrinol, Domaine Univ Sart Tilman, B-4000 Liege, Belgium. EM albert.beckers@chu.ulg.ac.be; stratakc@mail.nih.gov RI Jaffrain-Rea, Marie-Lise/D-1129-2009; Trivellin, Giampaolo/J-6583-2016; Daly, Adrian /E-2178-2011; OI Jaffrain-Rea, Marie-Lise/0000-0002-5916-8997; Trivellin, Giampaolo/0000-0003-2384-4153; Daly, Adrian /0000-0001-6130-2975; Rostomyan, Liliya/0000-0003-3784-2132; Mantovani, Giovanna/0000-0002-9065-3886; Pellegata, Natalia S./0000-0002-8000-7784 FU US Department of Health and Human Services-National Institutes of Health-National Institute of Child Health and Human Development [Z01-HD008920]; US Department of Health and Human Services-National Institutes of Health-National Human Genome Research Institute [U54HG006542]; Fonds D'Investissement de Recherche Scientifique, CHU de Liege; Jabbs Foundation; National Institute of Neurological Disorders and Stroke (NINDS) [R01 NS058529] FX This study was supported by the US Department of Health and Human Services-National Institutes of Health-National Institute of Child Health and Human Development (Z01-HD008920), US Department of Health and Human Services-National Institutes of Health-National Human Genome Research Institute (U54HG006542), Fonds D'Investissement de Recherche Scientifique, CHU de Liege, Jabbs Foundation, and National Institute of Neurological Disorders and Stroke (NINDS) (R01 NS058529). NR 55 TC 33 Z9 33 U1 2 U2 7 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2015 VL 22 IS 3 BP 353 EP 367 DI 10.1530/ERC-15-0038 PG 15 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CO2RE UT WOS:000359003500018 PM 25712922 ER PT J AU Sousa, SF Gomez, RS Diniz, MG Bernardes, VF Soares, FFC Brito, JAR Liu, S Pontes, HAR Stratakis, CA Gomes, CC AF Sousa, Silvia F. Gomez, Ricardo S. Diniz, Marina G. Bernardes, Vanessa F. Soares, Flavia F. C. Brito, Joao Artur R. Liu, Sophie Pontes, Helder Antonio R. Stratakis, Constantine A. Gomes, Carolina C. TI Defects of the Carney complex gene (PRKAR1A) in odontogenic tumors SO ENDOCRINE-RELATED CANCER LA English DT Article DE mixed odontogenic tumors; ameloblastic fibroma; ameloblastic fibro-odontoma; ameloblastic fibrodentinoma; ameloblastic fibrosarcoma; loss of heterozygosity; benign tumors ID REGULATORY SUBUNIT; PTCH GENE; MUTATIONS; EXPRESSION; HETEROZYGOSITY; HETEROGENEITY; MYXOMA; CANCER; LEADS AB The surgical treatment of some odontogenic tumors often leads to tooth and maxillary bone loss as well as to facial deformity. Therefore, the identification of genes involved in the pathogenesis of odontogenic tumors may result in alternative molecular therapies. The PRKAR1A gene displays a loss of protein expression as well as somatic mutations in odontogenic myxomas, an odontogenic ectomesenchymal neoplasm. We used a combination of quantitative RT-PCR (qRT-PCR), immunohistochemistry, loss of heterozygosity (LOH) analysis, and direct sequencing of all PRKAR1A exons to assess if this gene is altered in mixed odontogenic tumors. Thirteen tumors were included in the study: six ameloblastic fibromas, four ameloblastic fibro-odontomas, one ameloblastic fibrodentinoma, and two ameloblastic fibrosarcomas. The epithelial components of the tumors were separated from the mesenchymal by laser microdissection in most of the cases. We also searched for odontogenic pathology in Prkar1a(+/-) mice. PRKAR1A mRNA/protein expression was decreased in the benign mixed odontogenic tumors in association with LOH at markers around the PRKAR1A gene. We also detected a missense and two synonymous mutations along with two 5'-UTR and four intronic mutations in mixed odontogenic tumors. Prkar1a(+/-) mice did not show evidence of odontogenic tumor formation, which indicates that additional genes may be involved in the pathogenesis of such tumors, at least in rodents. We conclude that the PRKAR1A gene and its locus are altered in mixed odontogenic tumors. PRKAR1A expression is decreased in a subset of tumors but not in all, and Prkar1a(+/-) mice do not show abnormalities, which indicates that additional genes play a role in this tumor's pathogenesis. C1 [Sousa, Silvia F.; Gomez, Ricardo S.; Diniz, Marina G.; Soares, Flavia F. C.; Brito, Joao Artur R.] Univ Fed Minas Gerais UFMG, Dept Oral Surg & Pathol, Sch Dent, BR-31270901 Belo Horizonte, MG, Brazil. [Bernardes, Vanessa F.; Gomes, Carolina C.] Univ Fed Minas Gerais UFMG, Dept Pathol, Inst Biol Sci, BR-31270901 Belo Horizonte, MG, Brazil. [Liu, Sophie; Stratakis, Constantine A.] NIH, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, Bethesda, MD 20892 USA. [Pontes, Helder Antonio R.] Univ Fed Para UFPA, Joao de Barros Barreto Univ Hosp, Belem, Para, Brazil. RP Gomes, CC (reprint author), Univ Fed Minas Gerais UFMG, Dept Oral Surg & Pathol, Sch Dent, Ave Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil. EM carolinacgomes@ufmg.br RI SOUSA, SILVIA/M-5721-2015; Gomez, Ricardo/G-1976-2012; OI Gomez, Ricardo/0000-0001-8770-8009; GOMES, CAROLINA/0000-0003-1580-4995 FU intramural research program (IRP) of NICHD, NIH; Brazilian funding agency: Coordination for the Improvement of Higher Education Personnel (CAPES); Brazilian funding agency: Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG); Brazilian funding agency: National Council for Scientific and Technological Development (CNPq), Brazil FX This study was supported in part by the intramural research program (IRP) of NICHD, NIH, and by the following Brazilian funding agencies: Coordination for the Improvement of Higher Education Personnel (CAPES), Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), and the National Council for Scientific and Technological Development (CNPq), Brazil. R S Gomez and C C Gomes are research fellows at CNPq, and M G Diniz is a research fellow at CAPES. NR 29 TC 1 Z9 1 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2015 VL 22 IS 3 BP 399 EP 408 DI 10.1530/ERC-15-0094 PG 10 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CO2RE UT WOS:000359003500021 PM 25870248 ER PT J AU Dasari, A Phan, A Gupta, S Rashid, A Yeung, SCJ Hess, K Chen, H Tarco, E Chen, HQ Wei, CM Anh-Do, K Halperin, D Meric-Bernstam, F Yao, J AF Dasari, Arvind Phan, Alexandria Gupta, Sanjay Rashid, Asif Yeung, Sai-Ching Jim Hess, Kenneth Chen, Helen Tarco, Emily Chen, Huiqin Wei, Caimiao Anh-Do, Kim Halperin, Daniel Meric-Bernstam, Funda Yao, James TI Phase I study of the anti-IGF1R antibody cixutumumab with everolimus and octreotide in advanced well- differentiated neuroendocrine tumors SO ENDOCRINE-RELATED CANCER LA English DT Article DE IGF; neuroendocrine tumors; intracellular signaling; carcinoids ID GROWTH-FACTOR-I; RECEPTOR INHIBITOR; TARGETED-THERAPY; CANCER; EXPRESSION; RESISTANCE; SENSITIVITY; GENES; BETA; AKT AB Preclinical data suggest multiple roles for the IGF1 receptor (IGF1R) in neuroendocrine tumors (NETs), including mediating resistance to mammalian target of rapamycin (mTOR) inhibitors. Everolimus, an oral mTOR inhibitor, and octreotide long-acting repeatable (LAR) are approved for subgroups of well-differentiated NET. The primary objective of the present study was to establish the safety and recommended phase II dose (RP2D) of cixutumumab, a monoclonal antibody (MAB) against IGF1R, with everolimus and octreotide LAR. Patients with well-differentiated NET were treated with 10 mg everolimus p.o. daily, 20 mg octreotide LAR i.m. every 21 days, and escalating doses of cixutumumab. An expansion cohort was enrolled at RP2D. Correlative studies included the evaluation of mTOR pathway inhibition in paired tumor biopsies and the effects of this combination on metabolism via indirect calorimetry. Nineteen patients with progressive disease were enrolled, including nine to the expansion portion. Two patients had dose-limiting toxicities of grade 3 mucositis at 15 mg/kg cixutumumab. Long-term tolerance at RP2D was problematic, and the most common >= grade 3 adverse event was fatigue. One patient with metastatic insulinoma had a confirmed partial response, whereas 17 had stable disease. The median progression-free survival was 43.6 weeks, and the median overall survival was 25.5 months. The RP2D of this combination per the predefined study protocol of 10 mg/kg cixutumumab i.v., 20 mg octreotide LAR i.m. every 21 days plus 10 mg everolimus p.o. daily is associated with non-dose-limiting toxicities that limit long-term tolerance. Although a signal of activity was noted in the present study, this will need to be reconciled with limited tolerance of the combination and data from larger studies of anti-IGF1R MABs in NET that have been disappointing. C1 [Dasari, Arvind; Phan, Alexandria; Gupta, Sanjay; Rashid, Asif; Yeung, Sai-Ching Jim; Hess, Kenneth; Tarco, Emily; Chen, Huiqin; Wei, Caimiao; Anh-Do, Kim; Halperin, Daniel; Meric-Bernstam, Funda; Yao, James] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Chen, Helen] NCI, Rockville, MD USA. RP Yao, J (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe St,Unit 426, Houston, TX 77030 USA. EM jyao@mdanderson.org OI Halperin, Daniel M/0000-0002-3113-930X FU Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy [5U01CA062461]; NCATS Center for Clinical and Translational Sciences [UL1 TR000371]; Anderson Cancer Center Support [P30 CA016672]; Novartis FX Support was provided by the Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy (grant number 5U01CA062461 to J Yao), the NCATS Center for Clinical and Translational Sciences (grant number UL1 TR000371), the M.D. Anderson Cancer Center Support (grant number P30 CA016672), and Novartis. NR 29 TC 3 Z9 3 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2015 VL 22 IS 3 BP 431 EP 441 DI 10.1530/ERC-15-0002 PG 11 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CO2RE UT WOS:000359003500024 PM 25900182 ER PT J AU King, EE Qin, Y Toledo, RA Luo, A Ball, E Faucz, FR Janeway, KA Stratakis, CA Tomlinson, GE Dahia, PLM AF King, E. E. Qin, Y. Toledo, R. A. Luo, A. Ball, E. Faucz, F. R. Janeway, K. A. Stratakis, C. A. Tomlinson, G. E. Dahia, P. L. M. TI Integrity of the pheochromocytoma susceptibility TMEM127 gene in patients with pediatric malignancies SO ENDOCRINE-RELATED CANCER LA English DT Letter ID GERMLINE MUTATIONS; PARAGANGLIOMA; TUMOR C1 [King, E. E.; Qin, Y.; Toledo, R. A.; Luo, A.; Dahia, P. L. M.] Univ Texas Hlth Sci Ctr San Antonio UTHSCSA, Dept Med, San Antonio, TX 78229 USA. [Ball, E.; Faucz, F. R.; Stratakis, C. A.] NIH, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Janeway, K. A.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Childrens Hosp Canc Ctr, Boston, MA USA. [Tomlinson, G. E.] UTHSCSA, Dept Pediat, San Antonio, TX USA. [Tomlinson, G. E.; Dahia, P. L. M.] UTHSCSA, Greehey Children Canc Res Inst, San Antonio, TX USA. [Tomlinson, G. E.; Dahia, P. L. M.] UTHSCSA, Canc Therapy & Res Ctr, San Antonio, TX USA. RP Dahia, PLM (reprint author), Univ Texas Hlth Sci Ctr San Antonio UTHSCSA, Dept Med, San Antonio, TX 78229 USA. EM dahia@uthscsa.edu NR 7 TC 1 Z9 1 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2015 VL 22 IS 3 BP L5 EP L7 DI 10.1530/ERC-15-0101 PG 3 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CO2RE UT WOS:000359003500002 PM 25770152 ER PT J AU Lee, JM Trepel, JB Choyke, P Cao, L Sissung, T Houston, N Yu, MS Figg, WD Turkbey, IB Steinberg, SM Lee, MJ Ivy, SP Liu, JF Matulonis, UA Kohn, EC AF Lee, Jung-Min Trepel, Jane B. Choyke, Peter Cao, Liang Sissung, Tristan Houston, Nicole Yu, Minshu Figg, William D. Turkbey, Ismail Baris Steinberg, Seth M. Lee, Min-Jung Ivy, S. Percy Liu, Joyce F. Matulonis, Ursula A. Kohn, Elise C. TI CECs and IL-8 have prognostic and predictive utility in patients with recurrent platinum-sensitive ovarian cancer: biomarker correlates from the randomized phase-2 trial of olaparib and cediranib compared with olaparib in recurrent platinum-sensitive ovarian cancer SO FRONTIERS IN ONCOLOGY LA English DT Article DE CEC; IL-8; biomarkers; olaparib; cediranib; ovarian cancer ID CIRCULATING ENDOTHELIAL-CELLS; RESISTANT PROSTATE-CANCER; ADP-RIBOSE POLYMERASE; 0 CLINICAL-TRIAL; POLY(ADP-RIBOSE) POLYMERASE; RETROSPECTIVE ANALYSIS; MAINTENANCE THERAPY; MICROVESSEL DENSITY; PARP INHIBITORS; BREAST-CANCER AB Objective: Olaparib (O), a polyADPribose polymerase (PARP) inhibitor, and cediranib (C), a VEGF receptor (VEGFR)1-3 inhibitor together had greater activity than 0 alone in women with recurrent platinum-sensitive ovarian cancer (OvCa). The objective of this study is to identify potential lead biomarker candidates for response to O+C in the setting of a multi-institutional phase II study of 0 with and without C in recurrent platinum-sensitive OvCa. Methods: A self-selected group of patients participated in a prospectively planned exploratory biomarker substudy of the randomized phase II study of 0 versus O+C. Whole blood for peripheral blood mononuclear cell (PBMC) and plasma isolation was collected prior to and on day 3 of treatment. Quantitation of circulating endothelial cells (CEC), IL-6, IL-8, VEGF, and soluble VEGFR-2 plasma concentrations, and polyADPribose (PAR) incorporation were performed. Single nucleotide polymorphism analysis of XF?CC1 280H, R194W, and Q399R was done. Dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) was performed at baseline and day 3 of treatment. Parameter changes were compared between the two arms using an exact Wilcoxon rank sum test. Kaplan Meier and log-rank tests were used to examine survival outcome. Results: Thirteen patients elected to participate in the translational substudy, seven patients on 0 and six patients on O+C. Patients on O+C had a greater decrease in IL-8 concentration and larger CEC fold increase compared with those on 0 alone (p = 0.026, p = 0.032). The fold increase in CEC on day 3 was associated with duration of progression-free survival (PFS) (R-2 = 0.77, 95% Cl 0.55-0.97, p < 0.001). IL-8 post-pretreatment changes correlate with PFS (p = 0.028). XF?CC1 DNA polymorphisms were not related to PFS. All patients had reduction in PAR incorporation, and all except one had reduction in vascular flow on DCE-MRI. Conclusion: Our exploratory correlative studies indicate that CEC and IL-8 changes may be predictive for response to 0+ C and prognostic in recurrent platinum-sensitive OvCa, requiring prospective validation. C1 [Lee, Jung-Min; Trepel, Jane B.; Choyke, Peter; Cao, Liang; Sissung, Tristan; Houston, Nicole; Yu, Minshu; Figg, William D.; Turkbey, Ismail Baris; Steinberg, Seth M.; Lee, Min-Jung; Kohn, Elise C.] Ctr Canc Res, Bethesda, MD USA. [Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Liu, Joyce F.; Matulonis, Ursula A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, JM (reprint author), 10 Ctr Dr MSC1906,Bldg 10,Room 12N-226, Bethesda, MD 20892 USA. EM leej6@mail.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural Program of the Center for Cancer Research, National Cancer Institute, NIH; Cancer Therapy Evaluation Program of the NCI FX This correlative project was funded by the Intramural Program of the Center for Cancer Research, National Cancer Institute, NIH. The randomized phase-2 study was funded by the Cancer Therapy Evaluation Program of the NCI. Olaparib and cediranib were supplied under a Cooperative Research and Development Agreement between the NCI, NIH, Bethesda, MD, USA and AstraZeneca. The corresponding and senior authors had access to all the data and made the final decision to submit for publication. NR 52 TC 5 Z9 6 U1 0 U2 3 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2234-943X J9 FRONT ONCOL JI Front. Oncol. PD JUN 1 PY 2015 VL 5 AR 123 DI 10.3389/fonc.2015.00123 PG 8 WC Oncology SC Oncology GA CO4OP UT WOS:000359140600001 PM 26082895 ER PT J AU Vadyvaloo, V Viall, AK Jarrett, CO Hinz, AK Sturdevant, DE Hinnebusch, BJ AF Vadyvaloo, Viveka Viall, Austin K. Jarrett, Clayton O. Hinz, Angela K. Sturdevant, Daniel E. Hinnebusch, B. Joseph TI Role of the PhoP-PhoQ gene regulatory system in adaptation of Yersinia pestis to environmental stress in the flea digestive tract SO MICROBIOLOGY-SGM LA English DT Article ID BACTERIAL SENSOR KINASE; TOXIN-ANTITOXIN SYSTEMS; BIOFILM FORMATION; TRANSCRIPTIONAL REGULATION; ANTIMICROBIAL PEPTIDES; CHROMOSOMAL GENES; BIOVAR MICROTUS; BUBONIC PLAGUE; PH-6 ANTIGEN; EXPRESSION AB The Yersinia pestis PhoPQ gene regulatory system is induced during infection of the flea digestive tract and is required to produce adherent biofilm in the foregut, which greatly enhances bacterial transmission during a flea bite. To understand the in vivo context of PhoPQ induction and to determine PhoP-regulated targets in the flea, we undertook whole-genome comparative transcriptional profiling of Y. pestis WT and Delta phoP strains isolated from infected fleas and from temperature-matched in vitro planktonic and flow-cell biofilm cultures. In the absence of PhoP regulation, the gene expression program indicated that the bacteria experienced diverse physiological stresses and were in a metabolically less active state. Multiple stress response genes, including several toxin antitoxin loci and YhcN family genes responsible for increased acid tolerance, were upregulated in the phoP mutant during flea infection. The data implied that PhoPQ was induced by low pH in the flea gut, and that PhoP modulated physiological adaptation to acid and other stresses encountered during infection of the flea. This adaptive response, together with PhoP-dependent modification of the bacterial outer surface that includes repression of pH 6 antigen fimbriae, supports stable biofilm development in the flea foregut. C1 [Vadyvaloo, Viveka; Hinz, Angela K.] Washington State Univ, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA. [Viall, Austin K.; Jarrett, Clayton O.; Hinnebusch, B. Joseph] NIAID, Plague Sect, Lab Zoonot Pathogens, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Sturdevant, Daniel E.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Vadyvaloo, V (reprint author), Washington State Univ, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA. EM viveka@vetmed.wsu.edu FU Division of Intramural Research (National Institute of Allergy and Infectious Diseases/National Institutes of Health); National Institutes of Health [NIHR21AI097974] FX The research reported in this publication was supported by the Division of Intramural Research (National Institute of Allergy and Infectious Diseases/National Institutes of Health) and the National Institutes of Health (NIHR21AI097974) to V. V. We appreciate helpful comments from K. Tilly, D. Dulebohn, J. Shannon, D. Bland, C. Bosio, S. Dudte and L. Martinez to improve the manuscript. NR 67 TC 4 Z9 4 U1 3 U2 8 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JUN PY 2015 VL 161 BP 1198 EP 1210 DI 10.1099/mic.0.000082 PN 6 PG 13 WC Microbiology SC Microbiology GA CO3CW UT WOS:000359035200008 PM 25804213 ER PT J AU West, SK Munoz, BE Mkocha, H Gaydos, C Quinn, T AF West, Sheila K. Munoz, Beatriz E. Mkocha, Harran Gaydos, Charlotte Quinn, Thomas TI Risk of Infection with Chlamydia trachomatis from Migrants to Communities Undergoing Mass Drug Administration for Trachoma Control SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE Ocular Chlamydia trachomatis; population; prospective study; Tanzania; trachoma ID RANDOMIZED-TRIAL; AZITHROMYCIN; ELIMINATION; TANZANIA; HOUSEHOLDS; COVERAGE AB Purpose: To determine the risk of infection with Chlamydia trachomatis in children who are migrants to communities who are undergoing mass drug administration (MDA), and if their neighborhoods have higher rates of infection over time. Methods: In four communities in Kongwa, Tanzania, all children were enrolled in a longitudinal study of infection and trachoma. New children were identified at census updates as having not been in the community at the previous census. Within communities, neighborhoods were defined as spatially close groups of households, or "balozi". All children in the communities were invited to be examined for trachoma, and have ocular swabs taken for evidence of infection. Trachoma was graded using the World Health Organization simplified grading scheme, and swabs were processed using Amplicor. Results: Children who were migrants were more likely to be infected and to have trachoma than children who were resident in the community, which was significant by the time of the survey following the third year of MDA (odds ratio, OR, 2.49, 95% confidence interval, CI, 1.03-6.05). The neighborhoods where newcomers resided were more likely to have infection a year later than neighborhoods with no migrants, which was most pronounced following the third year of MDA (OR 2.86, 95% CI 1.07-7.65). Conclusion: Migrants to communities may be an important source of re-emergent infection, especially as MDA lowers infection among residents. Highly migrant populations may need a special surveillance and treatment program to avoid slowing progress in communities under MDA. C1 [West, Sheila K.; Munoz, Beatriz E.] Johns Hopkins Univ, Dana Ctr Prevent Ophthalmol, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Mkocha, Harran] Kongwa Trachoma Project, Kongwa, Tanzania. [Gaydos, Charlotte; Quinn, Thomas] Johns Hopkins Univ, Div Infect Dis, Int Chlamydia Lab, Baltimore, MD USA. [Quinn, Thomas] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP West, SK (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM shwest@jhmi.edu FU National Institutes of Health, National Eye Institute [EY022584]; Division of Intramural Research, NIAID, NIH FX This study was supported by a grant [EY022584] from the National Institutes of Health, National Eye Institute, and in part by the Division of Intramural Research, NIAID, NIH. NR 16 TC 5 Z9 5 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0928-6586 EI 1744-5086 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD JUN PY 2015 VL 22 IS 3 SI SI BP 170 EP 175 DI 10.3109/09286586.2015.1010687 PG 6 WC Ophthalmology SC Ophthalmology GA CO6QC UT WOS:000359280200006 PM 26158574 ER PT J AU Sommers, JA Suhasini, AN Brosh, RM AF Sommers, Joshua A. Suhasini, Avvaru N. Brosh, Robert M., Jr. TI Protein Degradation Pathways Regulate the Functions of Helicases in the DNA Damage Response and Maintenance of Genomic Stability SO BIOMOLECULES LA English DT Review ID WERNER-SYNDROME HELICASE; ANEMIA GROUP J; FANCONI-ANEMIA; BLOOMS-SYNDROME; UBIQUITIN LIGASES; HUMAN HLTF; HOMOLOGOUS RECOMBINATION; DEPENDENT DEGRADATION; REPLICATION STRESS; BLM DEGRADATION AB Degradation of helicases or helicase-like proteins, often mediated by ubiquitin-proteasomal pathways, plays important regulatory roles in cellular mechanisms that respond to DNA damage or replication stress. The Bloom's syndrome helicase (BLM) provides an example of how helicase degradation pathways, regulated by post-translational modifications and protein interactions with components of the Fanconi Anemia (FA) interstrand cross-link (ICL) repair pathway, influence cell cycle checkpoints, DNA repair, and replication restart. The FANCM DNA translocase can be targeted by checkpoint kinases that exert dramatic effects on FANCM stability and chromosomal integrity. Other work provides evidence that degradation of the F-box DNA helicase (FBH1) helps to balance translesion synthesis (TLS) and homologous recombination (HR) repair at blocked replication forks. Degradation of the helicase-like transcription factor (HLTF), a DNA translocase and ubiquitylating enzyme, influences the choice of post replication repair (PRR) pathway. Stability of the Werner syndrome helicase-nuclease (WRN) involved in the replication stress response is regulated by its acetylation. Turning to transcription, stability of the Cockayne Syndrome Group B DNA translocase (CSB) implicated in transcription-coupled repair (TCR) is regulated by a CSA ubiquitin ligase complex enabling recovery of RNA synthesis. Collectively, these studies demonstrate that helicases can be targeted for degradation to maintain genome homeostasis. C1 [Sommers, Joshua A.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. [Suhasini, Avvaru N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol & Med Oncol, San Antonio, TX 78229 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sommersj@mail.nih.gov; avvaru@uthscsa.edu; broshr@mail.nih.gov FU Intramural NIH HHS NR 85 TC 5 Z9 6 U1 7 U2 8 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2218-273X J9 BIOMOLECULES JI Biomolecules PD JUN PY 2015 VL 5 IS 2 BP 590 EP 616 DI 10.3390/biom5020590 PG 27 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CM4FV UT WOS:000357640800014 PM 25906194 ER PT J AU Sharma, I Sullivan, M McCutchan, TF AF Sharma, Indu Sullivan, Margery McCutchan, Thomas F. TI In Vitro Antimalarial Activity of Novel Semisynthetic Nocathiacin I Antibiotics SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PARASITE PLASMODIUM-FALCIPARUM; THIAZOLYL PEPTIDE ANTIBIOTICS; MALARIA PARASITE; PROTEIN-SYNTHESIS; RESISTANCE; APICOPLAST; SEQUENCE; SPREAD AB Presently, the arsenal of antimalarial drugs is limited and needs to be replenished. We evaluated the potential antimalarial activity of two water-soluble derivatives of nocathiacin (BMS461996 and BMS411886) against the asexual blood stages of Plasmodium falciparum. Nocathiacins are a thiazolyl peptide group of antibiotics, are structurally related to thiostrepton, have potent activity against a wide spectrum of multidrug-resistant Gram-positive bacteria, and inhibit protein synthesis. The in vitro growth inhibition assay was done using three laboratory strains of P. falciparum displaying various levels of chloroquine (CQ) susceptibility. Our results indicate that BMS461996 has potent antimalarial activity and inhibits parasite growth with mean 50% inhibitory concentrations (IC(50)s) of 51.55 nM for P. falciparum 3D7 (CQ susceptible), 85.67 nM for P. falciparum Dd2 (accelerated resistance to multiple drugs [ARMD]), and 99.44 nM for P. falciparum K1 (resistant to CQ, pyrimethamine, and sulfadoxine). Similar results at approximately 7-fold higher IC(50)s were obtained with BMS411886 than with BMS461996. We also tested the effect of BMS491996 on gametocytes; our results show that at a 20-fold excess of the mean IC50, gametocytes were deformed with a pyknotic nucleus and growth of stage I to IV gametocytes was arrested. This preliminary study shows a significant potential for nocathiacin analogues to be developed as antimalarial drug candidates and to warrant further investigation. C1 [Sharma, Indu] Hampton Univ, Dept Biol Sci, Hampton, VA 23668 USA. [Sullivan, Margery; McCutchan, Thomas F.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Sharma, I (reprint author), Hampton Univ, Dept Biol Sci, Hampton, VA 23668 USA. EM indu.sharma@hamptonu.edu FU Intramural Research Program of the Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health FX 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. NR 26 TC 4 Z9 4 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2015 VL 59 IS 6 BP 3174 EP 3179 DI 10.1128/AAC.04294-14 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CN7OF UT WOS:000358623200026 PM 25779576 ER PT J AU Dooley, KE Savic, RM Park, JG Cramer, Y Hafner, R Hogg, E Janik, J Marzinke, MA Patterson, K Benson, CA Hovind, L Dorman, SE Haas, DW AF Dooley, Kelly E. Savic, Radojka M. Park, Jeong-Gun Cramer, Yoninah Hafner, Richard Hogg, Evelyn Janik, Jennifer Marzinke, Mark A. Patterson, Kristine Benson, Constance A. Hovind, Laura Dorman, Susan E. Haas, David W. CA ACTG A5311 Study Team TI Novel Dosing Strategies Increase Exposures of the Potent Antituberculosis Drug Rifapentine but Are Poorly Tolerated in Healthy Volunteers SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID POPULATION PHARMACOKINETICS; PULMONARY TUBERCULOSIS; RIFAMPIN; INFECTION AB ` Rifapentine is a potent antituberculosis drug currently in phase III trials. Bioavailability decreases with increasing dose, yet high daily exposures are likely needed to improve efficacy and shorten the tuberculosis treatment duration. Further, the limits of tolerability are poorly defined. The phase I multicenter trial in healthy adults described here investigated two strategies to increase rifapentine exposures: dividing the dose or giving the drug with a high-fat meal. In arm 1, rifapentine was administered at 10 mg/kg of body weight twice daily and 20 mg/kg once daily, each for 14 days, separated by a 28-day washout; the dosing sequence was randomized. In arm 2, 15 mg/kg rifapentine once daily was given with a high-fat versus a low-fat breakfast. Sampling for pharmacokinetic analysis was performed on days 1 and 14. Population pharmacokinetic analyses were performed. This trial was stopped early for poor tolerability and because of safety concerns. Of 44 subjects, 20 discontinued prematurely; 11 of these discontinued for protocol-defined toxicity (a grade 3 or higher adverse event or grade 2 or higher rifamycin hypersensitivity). Taking rifapentine with a high-fat meal increased the median steady-state area under the concentration-time curve from time zero to 24 h (AUC(0-24ss)) by 31% (relative standard error, 6%) compared to that obtained when the drug was taken with a low-fat breakfast. Dividing the dose increased exposures substantially (e.g., 38% with 1,500 mg/day). AUC(0-24ss) was uniformly higher in our study than in recent tuberculosis treatment trials, in which toxicity was rare. In conclusion, two strategies to increase rifapentine exposures, dividing the dose or giving it with a high-fat breakfast, successfully increased exposures, but toxicity was common in healthy adults. The limits of tolerability in patients with tuberculosis remain to be defined. C1 [Dooley, Kelly E.; Marzinke, Mark A.; Dorman, Susan E.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Savic, Radojka M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Park, Jeong-Gun; Cramer, Yoninah] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Hafner, Richard] NIH, Div Aids, Bethesda, MD 20892 USA. [Hogg, Evelyn] Social & Sci Syst Inc, Silver Spring, MD USA. [Janik, Jennifer; Hovind, Laura] Frontier Sci Fdn, Amherst, NY USA. [Patterson, Kristine] Univ N Carolina, Chapel Hill, NC USA. [Benson, Constance A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Nashville, TN 37235 USA. RP Dooley, KE (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. EM kdooley1@jhmi.edu FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [UM1 AI068634, UM1 AI068636, UM1 AI106701]; [2UM1 AI069465]; [UL1 TR001079]; [K23AI080842]; [2UM1 AI069439-08]; [UL1 TR000445]; [UM1 AI069432]; [AI069423]; [1UL1 TR001111]; [P30 AI50410]; [U01 AI068634] FX The research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701. Other support was provided by the following: awards 2UM1 AI069465, UL1 TR001079, and K23AI080842 (to K.E.D.); 2UM1 AI069439-08 and UL1 TR000445 (to D.W.H.); UM1 AI069432 (to C.A.B.); AI069423, 1UL1 TR001111, and P30 AI50410 (to K.P.); and U01 AI068634 (to J.-G.P. and Y.C.). Sanofi provided the rifapentine for this study. NR 24 TC 3 Z9 3 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2015 VL 59 IS 6 BP 3399 EP 3405 DI 10.1128/AAC.05128-14 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CN7OF UT WOS:000358623200055 PM 25824215 ER PT J AU Woodham, AW Taylor, JR Jimenez, AI Skeate, JG Schmidt, T Brand, HE Da Silva, DM Kast, WM AF Woodham, Andrew W. Taylor, Julia R. Jimenez, Andrew I. Skeate, Joseph G. Schmidt, Thomas Brand, Heike E. Da Silva, Diane M. Kast, W. Martin TI Small molecule inhibitors of the annexin A2 heterotetramer prevent human papillomavirus type 16 infection SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE HPV16; annexin A2/S100A10 heterotetramer; A2t ID LEUKOCYTE PROTEASE INHIBITOR; II BINDS; CANCER; BURDEN; ENTRY AB Objectives: High-risk human papillomavirus (HPV) infection leads to the development of several human cancers that cause significant morbidity and mortality worldwide. HPV type 16 (HPV16) is the most common of the cancer-causing genotypes and gains entry to the basal cells of the epithelium through a non-canonical endocytic pathway that involves the annexin A2/S100A10 heterotetramer (A2t). A2t is composed of two annexin A2 monomers bound to an S100A10 dimer and this interaction is a potential target to block HPV16 infection. Here, recently identified small molecule inhibitors of A2t (A2ti) were investigated for their ability to prevent HPV16 infection in vitro. Methods: A2ti were added to HeLa cells in increasing concentrations prior to the addition of HPV16. Cytotoxicity was evaluated via trypan blue exclusion. HPV16 pseudovirion infection and fluorescently labelled HPV16 capsid internalization was measured with flow cytometry. Results: A2ti blocked HPV16 infection by 100% without substantial cellular toxicity or reduction in cell growth. Furthermore, A2ti blocked HPV16 entry into epithelial cells by 65%, indicating that the observed inhibition of HPV16 infection is in part due to a block in entry and that non-infectious entry may occur in the absence of A2t binding. Conclusions: These results demonstrate that targeting A2t may be an effective strategy to prevent HPV16 infection. C1 [Woodham, Andrew W.; Taylor, Julia R.; Jimenez, Andrew I.; Kast, W. Martin] Univ So Calif, Dept Mol Microbiol & Immunol, Los Angeles, CA 90089 USA. [Skeate, Joseph G.; Brand, Heike E.; Da Silva, Diane M.; Kast, W. Martin] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Schmidt, Thomas] NIDDK, Lab Chem Phys & Mol Biol, NIH, Bethesda, MD USA. [Da Silva, Diane M.; Kast, W. Martin] Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA. RP Kast, WM (reprint author), Univ So Calif, Dept Mol Microbiol & Immunol, 2011 Zonal Ave HMR 401, Los Angeles, CA 90089 USA. EM mkast@usc.edu FU NIH [R01 CA074397, RC2 CA148298, P30CA014089]; SC CTSI (NIH/NCRR/NCATS) [TL1TR000132]; ARCS Foundation; Short Term Education Program for Underrepresented Persons (STEP-UP) by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH [2R25-DK078385-07] FX This work was supported by NIH grants R01 CA074397 and RC2 CA148298 (to W. M. K.), and NIH grant P30CA014089 (Cancer Center Support Grant). A. W. W. was supported by a TL1 Scholar award from the SC CTSI (NIH/NCRR/NCATS) Grant # TL1TR000132, and by the ARCS Foundation John and Edith Leonis Award. A. I. J. was supported by the Short Term Education Program for Underrepresented Persons (STEP-UP) from grant no. 2R25-DK078385-07, entitled 'Kids Seek Cure for Kids' issued by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH. NR 18 TC 6 Z9 6 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2015 VL 70 IS 6 BP 1686 EP 1690 DI 10.1093/jac/dkv045 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA CN5YP UT WOS:000358510300012 PM 25712315 ER PT J AU Rodrigues, RF Zarate-Blades, CR Rios, WM Soares, LS Souza, PRM Brandao, IT Masson, AP Arnoldi, FGC Ramos, SG Letourneur, F Jacques, S Cagnard, N Chiocchia, G Silva, CL AF Rodrigues, Rodrigo F. Zarate-Blades, Carlos R. Rios, Wendy M. Soares, Luana S. Souza, Patricia R. M. Brandao, Izaira T. Masson, Ana P. Arnoldi, Frederico G. C. Ramos, Simone G. Letourneur, Franck Jacques, Sebastien Cagnard, Nicolas Chiocchia, Gilles Silva, Celio L. TI Synergy of chemotherapy and immunotherapy revealed by a genome-scale analysis of murine tuberculosis SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE drug therapy; vaccine therapy; gene expression profiling; lung transcriptome ID MYCOBACTERIUM-TUBERCULOSIS; DNA VACCINATION; EXPRESSION; CELLS; MICE; STRATEGIES; DISEASE; HSP65; ACTIVATION; BIOMARKERS AB Objectives: Although TB immunotherapy improves the results of conventional drug treatment, the effects of combining chemotherapy and immunotherapy have never been systematically evaluated. We used a comprehensive lung transcriptome analysis to directly compare the activity of combined chemotherapy and immunotherapy with that of single treatments in a mouse model of TB. Methods: Mycobacterium tuberculosis-infected mice in the chronic phase of the disease (day 30) received: (i) isoniazid and rifampicin (drugs) daily for 30 days; (ii) DNA immunotherapy (DNA), consisting of four 100 mu g injections at 10 day intervals; (iii) both therapies (DNA+ drugs); or (iv) saline. The effects were evaluated 10 days after the end of treatment (day 70 post-infection). Results: In all groups a systemic reduction in the load of bacilli was observed, bacilli became undetectable in the drugs and DNA+ drugs groups, but the whole lung transcriptome analysis showed 867 genes exclusively modulated by the DNA+ drugs combination. Gene enrichment analysis indicated that DNA+ drugs treatment provided synergistic effects, including the down-regulation of proinflammatory cytokines and mediators of fibrosis, as confirmed by real-time PCR, ELISA, histopathology and hydroxyproline assay. Conclusions: Our results provide a molecular basis for the advantages of TB treatment using combined chemotherapy and DNA immunotherapy and demonstrate the synergistic effects obtained with this strategy. C1 [Rodrigues, Rodrigo F.; Zarate-Blades, Carlos R.; Rios, Wendy M.; Soares, Luana S.; Souza, Patricia R. M.; Brandao, Izaira T.; Masson, Ana P.; Arnoldi, Frederico G. C.; Silva, Celio L.] Univ Sao Paulo, Ctr TB Res, Dept Biochem & Immunol, Ribeirao Preto Sch Med, BR-14049900 Ribeirao Preto, Brazil. [Ramos, Simone G.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pathol, BR-14049900 Sao Paulo, Brazil. [Letourneur, Franck; Jacques, Sebastien; Cagnard, Nicolas; Chiocchia, Gilles] Univ Paris 05, Inst Cochin, F-75014 Paris, France. [Letourneur, Franck; Jacques, Sebastien; Cagnard, Nicolas; Chiocchia, Gilles] CNRS CMRS 8104, INSERM U1016, F-75014 Paris, France. [Cagnard, Nicolas] Hop Necker Enfants Malad, F-75015 Paris, France. RP Zarate-Blades, CR (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zarate.blades@gmail.com RI Zarate-Blades, Carlos/C-9663-2015; chiocchia, gilles/F-6287-2013 OI Zarate-Blades, Carlos/0000-0002-7728-7869; chiocchia, gilles/0000-0001-9973-0940 FU Sao Paulo Research Foundation (FAPESP) [07/54880-0]; Conselho Nacional de Pesquisa (CNPq); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Financiadora de Estudos e Projetos (FINEP); Institut National de la Sante et de la Recherche Medicale (Inserm) FX This work was supported by Sao Paulo Research Foundation (FAPESP, grant #07/54880-0), Conselho Nacional de Pesquisa (CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Financiadora de Estudos e Projetos (FINEP) and Institut National de la Sante et de la Recherche Medicale (Inserm). NR 50 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2015 VL 70 IS 6 BP 1774 EP 1783 DI 10.1093/jac/dkv023 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA CN5YP UT WOS:000358510300022 PM 25687643 ER PT J AU Williams, CA Abbink, TEM Jeang, KT Lever, AML AF Williams, Claire A. Abbink, Truus E. M. Jeang, Kuan-Teh Lever, Andrew M. L. TI Identification of RNA helicases in human immunodeficiency virus 1 (HIV-1) replication - a targeted small interfering RNA library screen using pseudotyped and WT HIV-1 SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID FINGER ANTIVIRAL PROTEIN; P72; P68; MITOCHONDRIAL; INFECTION; DDX5 AB Central to the development of new treatments for human immunodeficiency virus 1 (HIV-1) is a more thorough understanding of the viral life cycle and the cellular cofactors upon which this depends. Targeting cellular proteins and their interaction with HIV-1 has the potential to reduce the problem of emerging viral resistance to drugs as mutational escape is more difficult. We performed a short interfering RNA (siRNA) library screen targeting 59 cellular RNA helicases, assessing the effect on both viral capsid protein production and infectious virion formation. Five RNA helicases were identified which, when knocked down, reproducibly decreased infectious particle production: DDX5, DDX10, DDX17, DDX28 and DDX52. Two of these proteins (DDX5 and DDX17) have known roles in HIV-1 replication. A further helicase (DDX10) was a positive hit from a previous genome-wide siRNA screen; however, DDX28 and DDX52 have not previously been implicated as essential cofactors for HIV-1. C1 [Williams, Claire A.; Abbink, Truus E. M.; Jeang, Kuan-Teh; Lever, Andrew M. L.] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England. [Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD USA. RP Lever, AML (reprint author), Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England. EM amll1@medschl.cam.ac.uk NR 26 TC 1 Z9 1 U1 1 U2 2 PU MICROBIOLOGY SOC PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER ST, LONDON WC1N 2JU, ERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD JUN PY 2015 VL 96 BP 1484 EP 1489 DI 10.1099/vir.0.000092 PN 6 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA CN1OJ UT WOS:000358189000029 PM 25701821 ER PT J AU Tersey, SA Bolanis, E Holman, TR Maloney, DJ Nadler, JL Mirmira, RG AF Tersey, Sarah A. Bolanis, Esther Holman, Theodore R. Maloney, David J. Nadler, Jerry L. Mirmira, Raghavendra G. TI 12-Lipoxygenase and Islet beta-Cell Dysfunction in Diabetes SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID ENDOPLASMIC-RETICULUM STRESS; ADIPOSE-TISSUE INFLAMMATION; PANCREATIC-ISLETS; INSULIN-SECRETION; MOUSE MODEL; SELECTIVE INHIBITORS; ARACHIDONIC-ACID; DEFICIENT MICE; OXIDATIVE MODIFICATION; 12-HUMAN LIPOXYGENASE AB The insulin producing islet beta-cells have increasingly gained attention for their role in the pathogeneses of virtually all forms of diabetes. Dysfunction, de-differentiation, and/or death of beta-cells are pivotal features in the transition from normoglycemia to hyperglycemia in both animal models of metabolic disease and humans. In both type 1 and type 2 diabetes, inflammation appears to be a central cause of beta-cell derangements, and molecular pathways that modulate inflammation or the inflammatory response are felt to be prime targets of future diabetes therapy. The lipoxygenases (LOs) represent a class of enzymes that oxygenate cellular polyunsaturated fatty acids to produce inflammatory lipid intermediates that directly and indirectly affect cellular function and survival. The enzyme 12-LO is expressed in all metabolically active tissues, including pancreatic islets, and has received increasing attention for its role in promoting cellular inflammation in the setting of diabetes. Genetic deletion models of 12-LO in mice reveal striking protection from metabolic disease and its complications and an emerging body of literature has implicated its role in human disease. This review focuses on the evidence supporting the proinflammatory role of 12-LO as it relates to islet beta-cells, and the potential for 12-LO inhibition as a future avenue for the prevention and treatment of metabolic disease. C1 [Tersey, Sarah A.; Mirmira, Raghavendra G.] Indiana Univ, Dept Pediat, Sch Med, Indianapolis, IN 46202 USA. [Tersey, Sarah A.; Mirmira, Raghavendra G.] Indiana Univ, Ctr Diabet & Metab Dis, Sch Med, Indianapolis, IN 46202 USA. [Bolanis, Esther; Mirmira, Raghavendra G.] Indiana Univ, Dept Biochem & Mol Biol, Sch Med, Indianapolis, IN 46202 USA. [Mirmira, Raghavendra G.] Indiana Univ, Dept Med, Sch Med, Indianapolis, IN 46202 USA. [Mirmira, Raghavendra G.] Indiana Univ, Dept Cellular & Integrat Physiol, Sch Med, Indianapolis, IN 46202 USA. [Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. [Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Nadler, Jerry L.] Eastern Virginia Med Sch, Dept Med & Strelitz Diabet Ctr, Norfolk, VA 23507 USA. RP Mirmira, RG (reprint author), 635 Barnhill Dr, Indianapolis, IN 46202 USA. EM rmirmira@iu.edu OI Tersey, Sarah/0000-0003-0667-2361 FU American Diabetes Junior Faculty Award; American Physiological Society Porter Fellowship; National Institutes of Health [R01 DK083583, R01 DK060581, R01 AG047986, R01 HL112605]; Juvenile Diabetes Research Foundation; Ball Brothers Foundation; George and Francis Ball Foundation FX This work was supported by an American Diabetes Junior Faculty Award (S.A.T.); an American Physiological Society Porter Fellowship (E.B.); National Institutes of Health Grants R01 DK083583 and R01 DK060581 (to R.G.M.), R01 AG047986 (to T.R.H.), and R01 HL112605 (to J.L.N.); a grant from the Juvenile Diabetes Research Foundation (J.L.N. and T.R.H.); and grants from the Ball Brothers Foundation and the George and Francis Ball Foundation (R.G.M.). NR 118 TC 4 Z9 4 U1 1 U2 9 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2015 VL 29 IS 6 BP 791 EP 800 DI 10.1210/me.2015-1041 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CN6HA UT WOS:000358534000002 PM 25803446 ER PT J AU Kamran, F Andrade, AC Nella, AA Clokie, SJ Rezvani, G Nilsson, O Baron, J Lui, JC AF Kamran, Fariha Andrade, Anenisia C. Nella, Aikaterini A. Clokie, Samuel J. Rezvani, Geoffrey Nilsson, Ola Baron, Jeffrey Lui, Julian C. TI Evidence That Up-Regulation of MicroRNA-29 Contributes to Postnatal Body Growth Deceleration SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GENETIC PROGRAM; DOWN-REGULATION; NUCLEAR EXPORT; TRANSLATION; MIR-29; INITIATION; MIRBASE; TARGETS; CELLS; MICE AB Body growth is rapid in infancy but subsequently slows and eventually ceases due to a progressive decline in cell proliferation that occurs simultaneously in multiple organs. We previously showed that this decline in proliferation is driven in part by postnatal down-regulation of a large set of growth-promoting genes in multiple organs. We hypothesized that this growth-limiting genetic program is orchestrated by microRNAs (miRNAs). Bioinformatic analysis identified target sequences of the miR-29 family of miRNAs to be overrepresented in age-down-regulated genes. Concomitantly, expression microarray analysis in mouse kidney and lung showed that all members of the miR-29 family, miR-29a, -b, and -c, were strongly up-regulated from 1 to 6 weeks of age. Real-time PCR confirmed that miR-29a, -b, and -c were up-regulated with age in liver, kidney, lung, and heart, and their expression levels were higher in hepatocytes isolated from 5-week-old mice than in hepatocytes from embryonic mouse liver at embryonic day 16.5. We next focused on 3 predicted miR-29 target genes (Igf1, Imp1, and Mest), all of which are growth-promoting. A 3'-untranslated region containing the predicted target sequences from each gene was placed individually in a luciferase reporter construct. Transfection of miR-29 mimics suppressed luciferase gene activity for all 3 genes, and this suppression was diminished by mutating the target sequences, suggesting that these genes are indeed regulated by miR-29. Taken together, the findings suggest that up-regulation of miR-29 during juvenile life drives the down-regulation of multiple growth-promoting genes, thus contributing to physiological slowing and eventual cessation of body growth. C1 [Kamran, Fariha; Nella, Aikaterini A.; Rezvani, Geoffrey; Baron, Jeffrey; Lui, Julian C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Dev, NIH, Bethesda, MD 20892 USA. [Clokie, Samuel J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. [Andrade, Anenisia C.; Nilsson, Ola] Karolinska Inst, Ctr Mol Med, SE-17176 Stockholm, Sweden. [Andrade, Anenisia C.; Nilsson, Ola] Karolinska Inst, Dept Womens & Childrens Hlth, Pediat Endocrinol Unit, SE-17176 Stockholm, Sweden. Karolinska Univ Hosp, SE-17176 Stockholm, Sweden. RP Lui, JC (reprint author), NIH, Sect Growth & Dev, CRC, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM luichunk@mail.nih.gov RI Lui, Chun Kin Julian/E-2253-2012; OI Clokie, Samuel/0000-0002-0025-3652 FU Intramural Research Program of Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Swedish Research Council [2012-99X-221998-01-3, K2015-54X-22736-01-4]; Karolinska Institutet; Swedish Society of Medicine; Stiftelsen Frimurare Barnhuset Stockholm; Sallskapet Barnavard; HKH Kronprinsessan Lovisas Forening for Barnasjukvard FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. O.N. and A.C.A. were supported by the Swedish Research Council (Project 2012-99X-221998-01-3 and K2015-54X-22736-01-4), Karolinska Institutet, the Swedish Society of Medicine, Stiftelsen Frimurare Barnhuset Stockholm, Sallskapet Barnavard, and HKH Kronprinsessan Lovisas Forening for Barnasjukvard. NR 30 TC 2 Z9 2 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2015 VL 29 IS 6 BP 921 EP 932 DI 10.1210/me.2015-1047 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CN6HA UT WOS:000358534000012 PM 25866874 ER PT J AU Kato, J Vekhter, D Heath, J Zhu, J Barbieri, JT Moss, J AF Kato, J. Vekhter, D. Heath, J. Zhu, J. Barbieri, J. T. Moss, J. TI Mutations of the functional ARH1 allele in tumors from ARH1 heterozygous mice and cells affect ARH1 catalytic activity, cell proliferation and tumorigenesis SO ONCOGENESIS LA English DT Article ID ADP-RIBOSYLARGININE HYDROLASES; HUMAN NEUTROPHIL PEPTIDE-1; TURKEY ERYTHROCYTES; CHOLERA-TOXIN; RIBOSYLATION; PROTEIN; IDENTIFICATION; ARGININE; ACTIN; RAS AB ADP-ribosylation results from transfer of the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD) to an acceptor with ADP-ribose-acceptor content determined by the activities of ADP-ribosyltransferases, which modify the acceptor, and ADP-ribose-acceptor hydrolase (ARH), which cleave the ADP-ribose-acceptor bond. ARH1 was discovered as an ADP-ribose(arginine) protein hydrolase. Previously, we showed that ARH1-knockout and ARH1 heterozygous mice spontaneously developed tumors. Further, ARH1-knockout and ARH1 heterozygous mouse embryonic fibroblasts (MEFs) produced tumors when injected into nude mice. In tumors arising in ARH1 heterozygous mice and MEFs, we found both loss of heterozygosity (LOH) of the ARH1 gene and ARH1 gene mutations. In the present report, we found that these mutant ARH1 genes encode proteins with reduced ARH1 enzymatic activity. Moreover, MEFs transformed with ARH1 mutant genes exhibiting different levels of ARH1 activity showed altered rates of proliferation, anchorage-independent colony growth in soft agar, and tumorigenesis in nude mice. MEFs transformed with the wildtype (WT) gene, but expressing low levels of hydrolase activity were also tumorigenic. However, transformation with the WT gene was less likely to yield tumors than transformation with a mutant gene exhibiting similar hydrolase activity. Thus, control of protein-ADP-ribosylation by ARH1 is critical for tumorigenesis. In the human cancer database, LOH and mutations of the ARH1 gene were observed. Further, ARH1 gene mutations were located in exons 3 and 4, comparable to exons 2 and 3 of the murine ARH1 gene, which comprise the catalytic site. Thus, human ARH1 gene mutations similar to their murine counterparts may be involved in human cancers. C1 [Kato, J.; Vekhter, D.; Heath, J.; Zhu, J.; Moss, J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Barbieri, J. T.] Med Coll Wisconsin, Microbiol & Mol Genet, Milwaukee, WI 53226 USA. RP Moss, J (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 6D05 MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov FU Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute; NIH [AI030162] FX This study was supported by the Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute. JTB was supported by NIH grant AI030162. NR 43 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2157-9024 J9 ONCOGENESIS JI Oncogenesis PD JUN PY 2015 VL 4 AR e151 DI 10.1038/oncsis.2015.5 PG 9 WC Oncology SC Oncology GA CN8UF UT WOS:000358718900002 PM 26029825 ER PT J AU Jackson, JC Albert, PS Zhang, ZW AF Jackson, John C. Albert, Paul S. Zhang, Zhiwei TI A TWO-STATE MIXED HIDDEN MARKOV MODEL FOR RISKY TEENAGE DRIVING BEHAVIOR SO ANNALS OF APPLIED STATISTICS LA English DT Article DE Adaptive quadrature; hidden Markov model; joint model; random effects ID LONGITUDINAL DATA; TRIAL DATA; ALGORITHMS; DRIVERS AB This paper proposes a joint model for longitudinal binary and count outcomes. We apply the model to a unique longitudinal study of teen driving where risky driving behavior and the occurrence of crashes or near crashes are measured prospectively over the first 18 months of licensure. Of scientific interest is relating the two processes and predicting crash and near crash outcomes. We propose a two-state mixed hidden Markov model whereby the hidden state characterizes the mean for the joint longitudinal crash/near crash outcomes and elevated g-force events which are a proxy for risky driving. Heterogeneity is introduced in both the conditional model for the count outcomes and the hidden process using a shared random effect. An estimation procedure is presented using the forward-backward algorithm along with adaptive Gaussian quadrature to perform numerical integration. The estimation procedure readily yields hidden state probabilities as well as providing for a broad class of predictors. C1 [Jackson, John C.] US Mil Acad, Dept Math Sci, West Point, NY 10996 USA. [Albert, Paul S.; Zhang, Zhiwei] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Biostat & Bioinformat, Bethesda, MD 20892 USA. RP Jackson, JC (reprint author), US Mil Acad, Dept Math Sci, Thayer Hall, West Point, NY 10996 USA. EM john.jackson@usma.edu; albertp@mail.nih.gov FU Intramural Research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Supported by the Intramural Research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 19 TC 0 Z9 0 U1 1 U2 5 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD JUN PY 2015 VL 9 IS 2 BP 849 EP 865 DI 10.1214/14-AOAS765 PG 17 WC Statistics & Probability SC Mathematics GA CN3ZR UT WOS:000358368000014 PM 27766124 ER PT J AU Vanpouille, C Lisco, A Grivel, JC Bassit, LC Kauffman, RC Sanchez, J Schinazi, RF Lederman, MM Rodriguez, B Margolis, L AF Vanpouille, Christophe Lisco, Andrea Grivel, Jean-Charles Bassit, Leda C. Kauffman, Robert C. Sanchez, Jorge Schinazi, Raymond F. Lederman, Michael M. Rodriguez, Benigno Margolis, Leonid TI Valacyclovir Decreases Plasma HIV-1 RNA in HSV-2 Seronegative Individuals: A Randomized Placebo-Controlled Crossover Trial SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV-1; HSV-2; acyclovir; herpesvirus; reverse transcriptase inhibitor ID HERPES-SIMPLEX-VIRUS; REVERSE-TRANSCRIPTASE INHIBITOR; ACYCLOVIR SUPPRESSIVE THERAPY; STANDARD-DOSE ACYCLOVIR; DUALLY INFECTED PERSONS; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; ANTIVIRAL ACTIVITY; DOUBLE-BLIND; WOMEN AB Background. Acyclovir (ACV), a highly specific anti-herpetic drug, acts as a DNA chain terminator for several human herpesviruses (HHVs), including HHV-2 (HSV-2), a common human immunodeficiency virus (HIV)-1 copathogen. Several trials demonstrated that HSV-2 suppressive therapy using ACV or its prodrug valacyclovir (valACV) reduced plasma HIV-1 viral load (VL) in HIV-1/HSV-2 coinfected persons, and this was proposed to be due to a decrease in generalized immune activation. Recently, however, we found that ACV directly suppresses HIV-1 ex vivo in tissues free of HSV-2 but endogenously coinfected with other HHVs. Here, we asked whether valACV suppresses VL in HIV-1 infected HSV-2-seronegative persons. Methods. Eighteen HIV-1 infected HSV-2-seronegative individuals were randomly assigned in a double blind placebo-controlled, crossover trial. Eligible participants had CD4 cell counts of >= 500 cells/mu L and were not taking antiretroviral therapy. Subjects in group A received 12 weeks of valACV 500 mg given twice daily by mouth followed by 2 weeks of a no treatment washout and then 12 weeks of placebo; subjects in group B received 12 weeks of placebo followed by 2 weeks of no treatment washout and then 12 weeks of valACV 500 mg twice daily. Results. HIV-1 VL in plasma of patients treated with valACV 500 mg twice daily for 12 weeks was reduced on average by 0.37 log(10) copies/mL. Conclusions. These data indicate that the effects of valACV on HIV-1 replication are not related to the suppression of HSV-2-mediated inflammation and are consistent with a direct effect of ACV on HIV-1 replication. C1 [Vanpouille, Christophe; Lisco, Andrea; Grivel, Jean-Charles; Margolis, Leonid] NICHHD, NIH, Bethesda, MD 20892 USA. [Bassit, Leda C.; Kauffman, Robert C.; Schinazi, Raymond F.] Emory Univ, Sch Med, Dept Pediat, Ctr AIDS Res,Lab Biochem Pharmacol, Atlanta, GA USA. [Bassit, Leda C.; Kauffman, Robert C.; Schinazi, Raymond F.] VA Med Ctr, Atlanta, GA USA. [Sanchez, Jorge] Asociac Civil Impacta Salud & Educ, Lima, Peru. [Lederman, Michael M.; Rodriguez, Benigno] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA. [Lederman, Michael M.; Rodriguez, Benigno] Case Western Reserve Univ, Ctr AIDS Res, Cleveland, OH 44106 USA. [Lederman, Michael M.; Rodriguez, Benigno] Univ Hosp Case Med Ctr, Cleveland, OH USA. RP Lederman, MM (reprint author), Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA. EM lederman.michael@clevelandactu.org RI Schinazi, Raymond/B-6777-2017 FU Intramural Research Program of the National Institute of Child Health and Human Development, National Institute of Health (NIH); NIH Bench-to-Bedside Program; NIH [AI 68636, AI 76174, 2P30-AI-050409]; CWRU Center for AIDS Research [AI36219]; Department of Veterans Affairs FX This research was supported, in part, by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institute of Health (NIH) and by the NIH Bench-to-Bedside Program. M. M. L. and B. R. are supported in part by NIH grants AI 68636, AI 76174 and by the CWRU Center for AIDS Research AI36219. R. F. S. is partly supported by the NIH sponsored CFAR grant 2P30-AI-050409 and the Department of Veterans Affairs. NR 40 TC 3 Z9 3 U1 0 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 JUN 1 PY 2015 VL 60 IS 11 BP 1708 EP 1714 DI 10.1093/cid/civ172 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CM9ZP UT WOS:000358070500024 PM 25740794 ER PT J AU Schug, TT Blawas, AM Gray, K Heindel, JJ Lawler, CP AF Schug, Thaddeus T. Blawas, Ashley M. Gray, Kimberly Heindel, Jerrold J. Lawler, Cindy P. TI Elucidating the Links Between Endocrine Disruptors and Neurodevelopment SO ENDOCRINOLOGY LA English DT Editorial Material ID POLYCYCLIC AROMATIC-HYDROCARBONS; ORGANOPHOSPHATE PESTICIDE EXPOSURE; INNER-CITY CHILDREN; PRENATAL PHTHALATE EXPOSURE; BEHAVIORAL-ASSESSMENT SCALE; BISPHENOL-A CONCENTRATIONS; MEXICAN-AMERICAN CHILDREN; DEVELOPING RAT-BRAIN; 1ST 3 YEARS; POLYCHLORINATED-BIPHENYLS AB Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes. C1 [Schug, Thaddeus T.; Gray, Kimberly; Heindel, Jerrold J.; Lawler, Cindy P.] NIEHS, Div Extramural Res & Training, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Blawas, Ashley M.] Duke Univ, Durham, NC 27708 USA. RP Schug, TT (reprint author), Div Extramural Res, 530 Davis Dr,Room 3041,Mail Drop K3-15, Morrisville, NC 27560 USA. EM schugt@niehs.nih.gov NR 95 TC 9 Z9 9 U1 2 U2 17 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2015 VL 156 IS 6 BP 1941 EP 1951 DI 10.1210/en.2014-1734 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CN4YB UT WOS:000358435400004 PM 25714811 ER PT J AU Li, FM Yang, J Jones, JE Villar, VM Yu, PY Armando, I Felder, RA Jose, PA AF Li, Fengmin Yang, Jian Jones, John Edward Villar, Van Anthony M. Yu, Peiying Armando, Ines Felder, Robin A. Jose, Pedro A. TI Sorting Nexin 5 and Dopamine D-1 Receptor Regulate the Expression of the Insulin Receptor in Human Renal Proximal Tubule Cells SO ENDOCRINOLOGY LA English DT Article ID OBESE ZUCKER RATS; BLOOD-PRESSURE; PHOSPHATIDYLINOSITOL 3-KINASE; ESSENTIAL-HYPERTENSION; FENOLDOPAM TREATMENT; CONVOLUTED TUBULE; DOWN-REGULATION; DIABETIC-RATS; PATHWAY; DEGRADATION AB Sorting nexin 5 (SNX5) belongs to the SNX family, which is composed of a diverse group of proteins that mediate trafficking of plasma membrane proteins, receptors, and transporters. SNX5 is important in the resensitization of the dopamine D-1-like receptor (D1R). D1R is uncoupled from its effector proteins in hypertension and diabetes, and treatment of diabetes restores D1R function and insulin receptor (IR) expression. We tested the hypothesis that the D1R and SNX5 regulate IR by studying the expression, distribution, dynamics, and functional consequences of their interaction in human renal proximal tubule cells (hRPTCs). D1R, SNX5, and IR were expressed and colocalized in the brush border of RPTs. Insulin promoted the colocalization of SNX5 and IR at the perinuclear area of hRPTCs. Unlike SNX5, the D1R colocalized and coimmunoprecipitated with IR, and this interaction was enhanced by insulin. To evaluate the role of SNX5 and D1R on IR signaling, we silenced via RNA interference the endogenous expression of SNX5 or the D1R gene DRD1 in hRPTCs. We observed a decrease in IR expression and abundance of phosphorylated IR substrate and phosphorylated protein kinase B, which are crucial components of the IR signal transduction pathway. Our data indicate that SNX5 and D1R are necessary for normal IR expression and activity. It is conceivable that D1R and SNX5 may interact to increase the sensitivity to insulin via a positive regulation of IR and insulin signaling. C1 [Li, Fengmin; Jose, Pedro A.] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20057 USA. [Li, Fengmin] Natl Inst Diabet & Digest & Kidney Dis, NIH, Liver Dis Branch, Bethesda, MD 20892 USA. [Yang, Jian] Third Mil Med Univ, Dept Nutr, Daping Hosp, Chongqing 400042, Peoples R China. [Yang, Jian; Jones, John Edward; Villar, Van Anthony M.; Yu, Peiying; Armando, Ines; Jose, Pedro A.] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Jose, Pedro A.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Jose, Pedro A.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Felder, Robin A.] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. RP Jose, PA (reprint author), Univ Maryland, Sch Med, Div Nephrol, Dept Med, 20 Penn St,Suite S005D, Baltimore, MD 21201 USA. EM pjose@medicine.umaryland.edu FU United States National Institutes of Health [R01HL092196, R37HL023081, R01DK090918]; National Natural Science Foundation of China [81100500, 30925018] FX These studies were supported in part by United States National Institutes of Health Grants R01HL092196, R37HL023081, and R01DK090918 and National Natural Science Foundation of China Grants 81100500 and 30925018. NR 49 TC 0 Z9 0 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2015 VL 156 IS 6 BP 2211 EP 2221 DI 10.1210/en.2014-1638 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CN4YB UT WOS:000358435400028 PM 25825816 ER PT J AU Huang, CCJ Kraft, C Moy, N Ng, L Forrest, D AF Huang, Chen-Che Jeff Kraft, Cary Moy, Nicole Ng, Lily Forrest, Douglas TI A Novel Population of Inner Cortical Cells in the Adrenal Gland That Displays Sexually Dimorphic Expression of Thyroid Hormone Receptor-beta 1 SO ENDOCRINOLOGY LA English DT Article ID X-ZONE; CONE PHOTORECEPTORS; GONADAL DEVELOPMENT; PROGENITOR CELLS; C-ERBA; MOUSE; FETAL; CORTEX; MICE; RESISTANCE AB The development of the adrenal cortex involves the formation and then subsequent regression of immature or fetal inner cell layers as the mature steroidogenic outer layers expand. However, controls over this remodeling, especially in the immature inner layer, are incompletely understood. Here we identify an inner cortical cell population that expresses thyroid hormone receptor-beta 1 (TR beta 1), one of two receptor isoforms encoded by the Thrb gene. Using mice with a Thrb(b1) reporter allele that expresses lacZ instead of TR beta 1, beta-galactosidase was detected in the inner cortex from early stages. Expression peaked at juvenile ages in an inner zone that included cells expressing 20-alpha-hydroxysteroid dehydrogenase, a marker of the transient, so-called X-zone in mice. The beta-galactosidase- positive zone displayed sexually dimorphic regression in males after approximately 4 weeks of age but persisted in females into adulthood in either nulliparous or parous states. T-3 treatment promoted hypertrophy of inner cortical cells, induced some markers of mature cortical cells, and, in males, delayed the regression of the TR beta 1-positive zone, suggesting that TR beta 1 could partly divert the differentiation fate and counteract male-specific regression of inner zone cells. TR beta 1-deficient mice were resistant to these actions of T-3, supporting a functional role for TR beta 1 in the inner cortex. C1 [Huang, Chen-Che Jeff; Kraft, Cary; Moy, Nicole; Ng, Lily; Forrest, Douglas] Natl Inst Diabet & Digest & Kidney Dis, NIH, Lab Endocrinol & Receptor Biol, Bethesda, MD 20892 USA. RP Forrest, D (reprint author), Natl Inst Diabet & Digest & Kidney Dis, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM forrestd@niddk.nih.gov FU intramural research program at the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health FX This work was supported by the intramural research program at the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. NR 59 TC 2 Z9 2 U1 4 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2015 VL 156 IS 6 BP 2338 EP 2348 DI 10.1210/en.2015-1118 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CN4YB UT WOS:000358435400038 PM 25774556 ER PT J AU Ashkenasy, N Schneider, J AF Ashkenasy, Nurit Schneider, Joel TI Functional Peptide and Protein Nanostructures SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Editorial Material C1 [Ashkenasy, Nurit] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. [Schneider, Joel] NCI, NIH, Bethesda, MD 20892 USA. RP Ashkenasy, N (reprint author), Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 1 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0021-2148 EI 1869-5868 J9 ISR J CHEM JI Isr. J. Chem. PD JUN PY 2015 VL 55 IS 6-7 SI SI BP 621 EP 621 DI 10.1002/ijch.201510007 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA CN0WB UT WOS:000358133600001 ER PT J AU Roschewski, M Dunleavy, K AF Roschewski, Mark Dunleavy, Kieron TI Secondary diffuse large B-cell lymphoma of the central nervous system: the need for better predictors SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID OCCULT LEPTOMENINGEAL DISEASE; NON-HODGKINS-LYMPHOMA; DOUBLE-HIT LYMPHOMA; RISK-FACTORS; ELDERLY-PATIENTS; FLOW-CYTOMETRY; RITUXIMAB ERA; INVOLVEMENT; PROPHYLAXIS; RECURRENCE C1 [Roschewski, Mark; Dunleavy, Kieron] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roschewski, M (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 4N-115, Bethesda, MD 20892 USA. EM mark.roschewski@nih.gov NR 18 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 2015 VL 56 IS 6 BP 1583 EP 1584 DI 10.3109/10428194.2015.1016936 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA CN2RP UT WOS:000358269900006 PM 26099732 ER PT J AU Kanemitsu, M John, D Lim, A Jaffe, ES Aoki, J AF Kanemitsu, Melanny John, David Lim, Anthony Jaffe, Elaine S. Aoki, Joseph TI Clonal Epstein-Barr virus-positive mucocutaneous ulcer mimicking a mature B-cell lymphoma in a patient with mycophenolate-induced immune suppression SO LEUKEMIA & LYMPHOMA LA English DT Letter ID LYMPHOPROLIFERATIVE-DISORDER; EBV C1 [Kanemitsu, Melanny; Aoki, Joseph] Clin Labs Hawaii, Aiea, HI 96701 USA. [John, David] Queens Med Ctr, Honolulu, HI USA. [Lim, Anthony] Hilo Med Ctr, Hilo, HI USA. [Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Aoki, J (reprint author), Clin Labs Hawaii, 98-1079 Moanalua Rd, Aiea, HI 96701 USA. EM joseph.aoki@hawaiilabs.com NR 15 TC 2 Z9 2 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 2015 VL 56 IS 6 BP 1908 EP 1910 DI 10.3109/10428194.2014.982646 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA CN2RP UT WOS:000358269900059 PM 25379620 ER PT J AU Xie, TW Lee, C Bolch, WE Zaidi, H AF Xie, Tianwu Lee, Choonsik Bolch, Wesley E. Zaidi, Habib TI Assessment of radiation dose in nuclear cardiovascular imaging using realistic computational models SO MEDICAL PHYSICS LA English DT Article DE radiation dosimetry; SPECT; PET; cardiovascular imaging; Monte Carlo ID POSITRON-EMISSION-TOMOGRAPHY; PERSONAL-COMPUTER SOFTWARE; MONTE-CARLO-SIMULATION; MYOCARDIAL-PERFUSION; KAWASAKI-DISEASE; HUMAN BIODISTRIBUTION; F-18-LABELED TRACER; PEDIATRIC-PATIENTS; NEWBORN PATIENT; CORONARY-ARTERY AB Purpose: Nuclear cardiology plays an important role in clinical assessment and has enormous impact on the management of a variety of cardiovascular diseases. Pediatric patients at different age groups are exposed to a spectrum of radiation dose levels and associated cancer risks different from those of adults in diagnostic nuclear medicine procedures. Therefore, comprehensive radiation dosimetry evaluations for commonly used myocardial perfusion imaging (MPI) and viability radiotracers in target population (children and adults) at different age groups are highly desired. Methods: Using Monte Carlo calculations and biological effects of ionizing radiation VII model, we calculate the S-values for a number of radionuclides (T1-201, Tc-99m, I-123, C-11, N-13, O-15, F-18, and Rb-82) and estimate the absorbed dose and effective dose for 12 MPI radiotracers in computational models including the newborn, 1-, 5-, 10-, 15-yr-old, and adult male and female computational phantoms. Results: For most organs, Tl-201 produces the highest absorbed dose whereas Rb-82 and O-15-water produce the lowest absorbed dose. For the newborn baby and adult patient, the effective dose of Rb-82 is 48% and 77% lower than that of Tc-99m-tetrofosmin (rest), respectively. Conclusions: Rb-82 results in lower effective dose in adults compared to Tc-99m-labeled tracers. However, this advantage is less apparent in children. The produced dosimetric databases for various radiotracers used in cardiovascular imaging, using new generation of computational models, can be used for risk-benefit assessment of a spectrum of patient population in clinical nuclear cardiology practice. (C) 2015 American Association of Physicists in Medicine. C1 [Xie, Tianwu; Zaidi, Habib] Univ Hosp Geneva, Div Nucl Med & Mol Imaging, CH-1211 Geneva 4, Switzerland. [Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. [Bolch, Wesley E.] Univ Florida, Dept Nucl & Radiol, Gainesville, FL 32611 USA. [Bolch, Wesley E.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA. [Zaidi, Habib] Univ Geneva, Geneva Neurosci Ctr, CH-1205 Geneva, Switzerland. [Zaidi, Habib] Univ Groningen, Univ Med Ctr Groningen, Dept Nucl Med & Mol Imaging, NL-9700 RB Groningen, Netherlands. RP Zaidi, H (reprint author), Univ Hosp Geneva, Div Nucl Med & Mol Imaging, CH-1211 Geneva 4, Switzerland. EM habib.zaidi@hcuge.ch RI Lee, Choonsik/C-9023-2015; OI Lee, Choonsik/0000-0003-4289-9870; Zaidi, Habib/0000-0001-7559-5297 NR 59 TC 1 Z9 1 U1 0 U2 9 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 JUN PY 2015 VL 42 IS 6 BP 2955 EP 2966 DI 10.1118/1.4921364 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998300023 PM 26127049 ER PT J AU Ellens, N Farahani, K AF Ellens, N. Farahani, K. TI Characterization of the Precision and Accuracy of a New, Preclinical, MRI-Guided Focused Ultrasound System for Image-Guided Interventions in Small-Bore, High-Field Magnets SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Ellens, N.] Johns Hopkins Univ, Baltimore, MD USA. [Farahani, K.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2015 VL 42 IS 6 BP 3263 EP 3264 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998301313 PM 26127396 ER PT J AU Ellens, N Partanen, A Ghoshal, G Burdette, E Farahani, K AF Ellens, N. Partanen, A. Ghoshal, G. Burdette, E. Farahani, K. TI Integration of Interstitial High Intensity Therapeutic Ultrasound Applicators On a Clinical MRI-Guided High Intensity Focused Ultrasound Treatment Planning Software Platform SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Ellens, N.] Johns Hopkins Univ, Baltimore, MD USA. [Partanen, A.] Philips Healthcare, Andover, MA USA. [Ghoshal, G.; Burdette, E.] Acoust Med Syst Inc, Savoy, IL USA. [Farahani, K.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2015 VL 42 IS 6 BP 3264 EP 3264 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998301314 PM 26127398 ER PT J AU Pyakuryal, A Lee, C Pelletier, C Jung, J Lee, C AF Pyakuryal, A. Lee, C. Pelletier, C. Jung, J. Lee, C. TI Development of Pre-Contoured Human Model Library in DICOM-RT Format for the Epidemiological Study of the Radiotherapy Patients SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Pyakuryal, A.; Lee, C.] NCI, Rockville, MD USA. [Lee, C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Pelletier, C.; Jung, J.] E Carolina Univ, Greenville, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 JUN PY 2015 VL 42 IS 6 BP 3285 EP 3285 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998301402 PM 26127484 ER PT J AU Pelletier, C Jung, J Lee, C Pyakuryal, A Kim, J Lee, C AF Pelletier, C. Jung, J. Lee, C. Pyakuryal, A. Kim, J. Lee, C. TI Evaluation of Selection Criteria for Computational Human Phantoms for Use in Out-Of-Field Organ Dosimetry for Radiotherapy Patients SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Pelletier, C.; Jung, J.] E Carolina Univ, Greenville, NC USA. [Lee, C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Pyakuryal, A.; Lee, C.] NCI, Rockville, MD USA. [Kim, J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2015 VL 42 IS 6 BP 3425 EP 3425 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998302105 PM 26128062 ER PT J AU Jung, J Lee, C Kim, J Pelletier, C Pyakuryal, A Lee, C AF Jung, J. Lee, C. Kim, J. Pelletier, C. Pyakuryal, A. Lee, C. TI Monte Carlo-Based Organ Dose Reconstruction Using Pre-Contoured Human Model for Hodgkins Lymphoma Patients Treated by Cobalt-60 External Beam Therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Jung, J.; Pelletier, C.] E Carolina Univ, Greenville, NC USA. [Lee, C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kim, J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Pyakuryal, A.; Lee, C.] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2015 VL 42 IS 6 BP 3464 EP 3464 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998302267 PM 26128222 ER PT J AU Bonfrate, A Farah, J De Marzi, L Delacroix, S Herault, J Sayah, R Lee, C Bolch, W Clairand, I AF Bonfrate, A. Farah, J. De Marzi, L. Delacroix, S. Herault, J. Sayah, R. Lee, C. Bolch, W. Clairand, I. TI Parametric Equation for Quick and Reliable Estimate of Stray Neutron Doses in Proton Therapy and Application for Intracranial Tumor Treatments SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Bonfrate, A.; Farah, J.; Sayah, R.; Clairand, I.] IRSN, Fontenay Aux Roses, France. [De Marzi, L.; Delacroix, S.] Inst Curie Ctr Protontherapie Orsay CPO, Orsay, France. [Herault, J.] Ctr Antoine Lacassagne CAL Cyclotron Biomed, Nice, France. [Lee, C.] NCI, Rockville, MD USA. [Bolch, W.] Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 JUN PY 2015 VL 42 IS 6 BP 3473 EP 3473 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998302304 ER PT J AU Atun, R Jaffray, D Coleman, N Van Dyk, J AF Atun, R. Jaffray, D. Coleman, N. Van Dyk, J. TI The Global Cancer Challenge: What Can We Do? SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Atun, R.] Harvard Univ, Cambridge, MA 02138 USA. [Jaffray, D.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Coleman, N.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Van Dyk, J.] Western Univ, London, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2015 VL 42 IS 6 BP 3564 EP 3564 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998302655 PM 26128705 ER PT J AU Kirby, J Tarbox, L Freymann, J Jaffe, C Prior, F AF Kirby, J. Tarbox, L. Freymann, J. Jaffe, C. Prior, F. TI The Cancer Imaging Archive: Supporting Radiomic and Imaging Genomic Research with Open-Access Data Sets SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Kirby, J.; Freymann, J.] Leidos Biomed Res Inc, Canc Imaging Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Tarbox, L.; Prior, F.] Washington Univ, Sch Med, St Louis, MO USA. [Jaffe, C.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 2 Z9 2 U1 1 U2 4 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 JUN PY 2015 VL 42 IS 6 BP 3587 EP 3587 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998303007 ER PT J AU Rao, A Net, J Brandt, K Huang, E Freymann, J Burnside, E Kirby, J Morris, E Bonaccio, E Giger, M Jaffe, C Ganott, M Sutton, E Le-Petross, H Zuley, M Dogan, B Whitman, G AF Rao, A. Net, J. Brandt, K. Huang, E. Freymann, J. Burnside, E. Kirby, J. Morris, E. Bonaccio, E. Giger, M. Jaffe, C. Ganott, M. Sutton, E. Le-Petross, H. Zuley, M. Dogan, B. Whitman, G. TI Identification of Associations Between Radiologist-Annotated Imaging Features and Genomic Alterations in Breast Invasive Carcinoma, a TCGA Phenotype Research Group Study SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Rao, A.; Net, J.] Univ Miami, Miami, FL USA. [Brandt, K.] Mayo Clin, Rochester, MN USA. [Huang, E.] NCI, NIH, Bethesda, MD 20892 USA. [Freymann, J.; Kirby, J.] Leidos Biomed Res Inc, Frederick, MD USA. [Burnside, E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Morris, E.; Sutton, E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bonaccio, E.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Giger, M.] Univ Chicago, Chicago, IL 60637 USA. [Jaffe, C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Ganott, M.; Zuley, M.] Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Pittsburgh, PA 15213 USA. [Le-Petross, H.; Dogan, B.; Whitman, G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2015 VL 42 IS 6 BP 3603 EP 3604 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998303066 PM 26128891 ER PT J AU Ahmed, M Graves, E Jeraj, R AF Ahmed, M. Graves, E. Jeraj, R. TI Beyond Radiation Induced Double Strand Breaks - a New Horizon for Radiation Therapy Research SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Ahmed, M.] NIH, New York, NY USA. [Graves, E.] Stanford Univ, Stanford, CA 94305 USA. [Jeraj, R.] Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2015 VL 42 IS 6 BP 3609 EP 3609 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998303085 PM 26128913 ER PT J AU Ferrara, K Chopra, R Konofagou, E Farahani, K AF Ferrara, K. Chopra, R. Konofagou, E. Farahani, K. TI Therapeutic Strategies and Image Guidance SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Ferrara, K.] Univ Calif Davis, Davis, CA USA. [Chopra, R.] UT SW Med Ctr Dallas, Dallas, TX USA. [Konofagou, E.] Columbia Univ, New York, NY 10027 USA. [Farahani, K.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 JUN PY 2015 VL 42 IS 6 BP 3624 EP 3625 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998303133 ER PT J AU Schulte, R Choy, H Taylor, P Lee, C Schulte, R AF Schulte, R. Choy, H. Taylor, P. Lee, C. Schulte, R. TI Clinical Trials in Proton and Particle Therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Schulte, R.; Schulte, R.] Loma Linda Univ, Loma Linda, CA 92350 USA. [Choy, H.] UT Southwestern Med Ctr, Dallas, TX USA. [Taylor, P.] UT MD Anderson Canc Ctr, Houston, TX USA. [Lee, C.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 JUN PY 2015 VL 42 IS 6 BP 3629 EP 3629 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998303148 PM 26129046 ER PT J AU Kruger, R Lee, C AF Kruger, R. Lee, C. TI CT Lung Cancer Screening Part 1 SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Kruger, R.] Marshfield Clin Fdn Med Res & Educ, Stevens Point, WI USA. [Lee, C.] Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2015 VL 42 IS 6 BP 3664 EP 3664 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998303272 PM 26129205 ER PT J AU Partanen, A Ellens, N Noureldine, S Burdette, E Tufano, R Farahani, K AF Partanen, A. Ellens, N. Noureldine, S. Burdette, E. Tufano, R. Farahani, K. TI Magnetic Resonance-Guided High-Intensity Focused Ultrasound for Localized Ablation of Head and Neck Tissue Structures: A Feasibility Study in An Animal Model SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Partanen, A.] Philips Healthcare, Andover, MA USA. [Ellens, N.; Noureldine, S.; Tufano, R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Burdette, E.] Acoust MedSyst Inc, Savoy, IL USA. [Farahani, K.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 JUN PY 2015 VL 42 IS 6 BP 3677 EP 3677 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998303313 PM 26129293 ER PT J AU Hazle, J Manning, H Keshari, K Clarke, L AF Hazle, J. Manning, H. Keshari, K. Clarke, L. TI The Joint AAPM-WMIS Symposium: Linking PreClinical and Clinical Trials: Co-Clinical Trials SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Hazle, J.] UT MD Anderson Canc Ctr, Houston, TX USA. [Manning, H.] Vanderbilt Univ, Nashville, TN 37235 USA. [Keshari, K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Clarke, L.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2015 VL 42 IS 6 BP 3680 EP 3680 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998303324 PM 26129307 ER PT J AU Deye, J Fraass, B Bortfeld, T Michalski, J AF Deye, J. Fraass, B. Bortfeld, T. Michalski, J. TI NIH-Funded Research, Clinical Trials and Program Projects SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) CY JUL 12-16, 2015 CL Anaheim, CA SP Amer Assoc Physicists Med C1 [Deye, J.] NCI, Bethesda, MD 20892 USA. [Fraass, B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Bortfeld, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Michalski, J.] Washington Univ, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 JUN PY 2015 VL 42 IS 6 BP 3690 EP 3691 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CL5KH UT WOS:000356998303357 PM 26129369 ER PT J AU Harmon, QE Baird, DD AF Harmon, Q. E. Baird, D. D. TI Use of depot medroxyprogesterone acetate and prevalent leiomyoma in young African American women SO HUMAN REPRODUCTION LA English DT Article DE leiomyoma; contraception; progesterone; African American women ID UTERINE LEIOMYOMAS; MITOTIC-ACTIVITY; FIBROIDS; CONTRACEPTION; EPIDEMIOLOGY; PATHOGENESIS AB STUDY QUESTION: Is use of depot medroxyprogesterone acetate (DMPA) a risk factor for or a protective factor against prevalent uterine leiomyoma? SUMMARY ANSWER: Ever use of DMPA was associated with a decreased risk (adjusted risk ratio (RR): 0.8,95% confidence interval (CI): 0.6, 0.9) of prevalent leiomyoma in young African American women. WHAT IS KNOWN ALREADY: Although progesterone is associated with growth of leiomyoma, previous epidemiological studies have shown a protective association for DMPA use. These previous studies may have been biased by studying clinically diagnosed leiomyoma (DMPA may mask symptoms thus delaying diagnoses). STUDY DESIGN, SIZE, DURATION: Cross sectional analysis of baseline data from a cohort study of 1696 African American women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Community-based recruitment (e.g. letters, flyers, radio and TV announcements) were used to enroll African American women between 23 and 34 years old without a previous diagnosis of leiomyoma in the Metropolitan Detroit area. Extensive questionnaire data were used to determine DMPA use and screening ultrasound detected the presence of leiomyoma >= 0.5 cm in diameter. Relative risks with adjustment for covariates were calculated for the presence of leiomyoma based on ever use of DMPA as well as duration and recency of use. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 1696 volunteers who enrolled, 43% had used DMPA. Leiomyoma were detected in 17% of those who had ever used DMPA compared with 26% of those who had never used DMPA. The reduction in prevalence remained after adjustment for potential confounders and was highest among women who had used DMPA for more than 4 years (adjusted RR: 0.5, 95% CI: 0.3, 0.8). The reduction in risk was seen for women whose most recent use was up to 8 years prior to study enrollment. LIMITATIONS, REASONS FOR CAUTION: The use of cross-sectional data means that the timing of initial fibroid development is not known, so the temporality of the association is uncertain. However in this sample of young women, most fibroids were small, suggesting that DMPA exposure may have occurred before leiomyoma development. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are in agreement with previous epidemiological studies, but protected from the bias inherent in the use of clinically diagnosed leiomyoma. Although further studies will be needed to elucidate the mechanism, use of DMPA as a contraceptive appears to provide long lasting protection against uterine leiomyoma. C1 [Harmon, Q. E.; Baird, D. D.] NIEHS, Womens Hlth Grp, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Harmon, QE (reprint author), NIEHS, Womens Hlth Grp, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM quaker.harmon@nih.gov RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Harmon, Quaker/0000-0002-5866-848X FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences; American Recovery and Reinvestment Act FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, and in part by funds allocated for health research by the American Recovery and Reinvestment Act. NR 22 TC 4 Z9 4 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2015 VL 30 IS 6 BP 1499 EP 1504 DI 10.1093/humrep/dev069 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CM9GJ UT WOS:000358015200025 PM 25820696 ER PT J AU Kane, AE Hilmer, SN Huizer-Pajkos, A Mach, J Nines, D Boyer, D Gavin, K Mitchell, SJ de Cabo, R AF Kane, Alice E. Hilmer, Sarah N. Huizer-Pajkos, Aniko Mach, John Nines, Dawn Boyer, Dawn Gavin, Kristan Mitchell, Sarah J. de Cabo, Rafael TI Factors that Impact on Interrater Reliability of the Mouse Clinical Frailty Index SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Letter C1 [Kane, Alice E.; Hilmer, Sarah N.] Univ Sydney, Royal N Shore Hosp, Dept Clin Pharmacol & Aged Care, Sydney, NSW 2006, Australia. [Huizer-Pajkos, Aniko] Royal N Shore Hosp, Kolling Inst Med Res, Dept Aged Care, Sydney, NSW, Australia. [Mach, John] Royal N Shore Hosp, Kolling Inst Med Res, Lab Ageing & Pharmacol, Sydney, NSW, Australia. [Nines, Dawn; Gavin, Kristan] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Boyer, Dawn] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [de Cabo, Rafael] NIA, Expt Gerontol Sect, Baltimore, MD 21224 USA. [Mitchell, Sarah J.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Kane, AE (reprint author), Univ Sydney, Royal N Shore Hosp, Dept Clin Pharmacol & Aged Care, Sydney, NSW 2006, Australia. EM alice.kane@sydney.edu.au RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Kane, Alice/0000-0002-4303-0491; , rafael/0000-0003-2830-5693 NR 2 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2015 VL 70 IS 6 BP 694 EP 695 DI 10.1093/gerona/glv032 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CM7MS UT WOS:000357878400004 PM 25838548 ER PT J AU Miller, RR Eastlack, M Hicks, GE Alley, DE Shardell, MD Orwig, DL Goodpaster, BH Chomentowski, PJ Hawkes, WG Hochberg, MC Ferrucci, L Magaziner, J AF Miller, Ram R. Eastlack, Marty Hicks, Gregory E. Alley, Dawn E. Shardell, Michelle D. Orwig, Denise L. Goodpaster, Bret H. Chomentowski, Peter J. Hawkes, William G. Hochberg, Marc C. Ferrucci, Luigi Magaziner, Jay TI Asymmetry in CT Scan Measures of Thigh Muscle 2 Months After Hip Fracture: The Baltimore Hip Studies SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Hip fracture; Muscle composition; Computed tomography; aged ID LOWER-EXTREMITY FUNCTION; NECROSIS-FACTOR-ALPHA; SKELETAL-MUSCLE; OLDER-ADULTS; FUNCTIONAL RECOVERY; BODY-COMPOSITION; STRENGTH; MASS; HEALTH; ATTENUATION AB Background. Hip fracture is an important problem for older adults with significant functional consequences. After hip fracture, reduced muscle loading can result in muscle atrophy. Methods. We compared thigh muscle characteristics in the fractured leg with those in the nonfractured leg in participants from the Baltimore Hip Studies 7th cohort using computed tomography (CT) scan imaging. Results. At 2 months postfracture, a single 10-mm axial CT scan was obtained at the midthigh level in 47 participants (26 men and 21 women) with a mean age of 80.4 years (range 65-96), and thigh muscle cross-sectional area (CSA), CSA of intermuscular adipose tissue (IMAT), as well as mean radiological attenuation were measured. Total thigh muscle CSA was less on the side of the fracture by 9.2 cm(2) (95% CI: 5.9, 12.4 cm(2)), whereas the CSA of IMAT was greater by 2.8 cm(2) (95% CI: 1.9, 3.8 cm(2)) on the fractured side. Mean muscle attenuation was lower on the side of the fracture by 3.61 HU (95% CI: 2.99, 4.24 HU). Conclusions. The observed asymmetry is consistent with the effect of disuse and inflammation in the affected limb along with training effects in the unaffected limb due to the favoring of this leg with ambulation during the postfracture period. C1 [Miller, Ram R.] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. [Miller, Ram R.; Alley, Dawn E.; Orwig, Denise L.; Hawkes, William G.; Magaziner, Jay] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Div Gerontol, Baltimore, MD 21201 USA. [Eastlack, Marty] Arcadia Univ, Dept Phys Therapy, Glenside, PA USA. [Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA. [Shardell, Michelle D.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Div Biostat & Bioinformat, Baltimore, MD 21201 USA. [Goodpaster, Bret H.; Chomentowski, Peter J.] Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA. [Hochberg, Marc C.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Miller, RR (reprint author), GlaxoSmithKline, Muscle Metab DPU, 5 Moore Dr N2-3213, Res Triangle Pk, NC 27709 USA. EM ram.6.miller@gsk.com FU National Institute on Aging [K23AG027746, R37 AG09901, R01 AG029315, P30 AG028747] FX National Institute on Aging (K23AG027746, R37 AG09901, R01 AG029315, P30 AG028747). NR 32 TC 1 Z9 1 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2015 VL 70 IS 6 BP 753 EP 756 DI 10.1093/gerona/glr188 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CM7MS UT WOS:000357878400013 PM 25958401 ER PT J AU Williams, JA Sink, KM Tooze, JA Atkinson, HH Cauley, JA Yaffe, K Tylavsky, FA Rubin, SM Simonsick, EM Kritchevsky, SB Houston, DK AF Williams, Julie A. Sink, Kaycee M. Tooze, Janet A. Atkinson, Hal H. Cauley, Jane A. Yaffe, Kristine Tylavsky, Frances A. Rubin, Susan M. Simonsick, Eleanor M. Kritchevsky, Stephen B. Houston, Denise K. TI Low 25-Hydroxyvitamin D Concentrations Predict Incident Depression in Well-Functioning Older Adults: The Health, Aging, and Body Composition Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Depression; Epidemiology; Risk factors; Nutrition ID VITAMIN-D DEFICIENCY; PARATHYROID-HORMONE; 1,25-DIHYDROXYVITAMIN D-3; GERIATRIC DEPRESSION; LATE-LIFE; COMMUNITY; METAANALYSIS; ASSOCIATION; POPULATION; SYMPTOMS AB Background. Cross-sectional studies suggest that low 25-hydroxyvitamin D (25[ OH] D) may be a risk factor for depression; however, there are few prospective studies. We examined the association between 25(OH) D and depressive symptoms in community-dwelling persons aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) Study (n = 2598). Methods. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D) at baseline and 2-, 3- and 4-year follow-up. Serum 25(OH) D was measured at 1-year follow-up and categorized as < 20, 20-<30, and >= 30 ng/mL. Mixed models were used to examine change in CES-D scores according to 25(OH) D categories. The association between 25(OH) D categories and incident depression (CES-D short score = 10 or antidepressant medication use) were assessed using Cox proportional hazards models. Analyses were adjusted for socio-demographic and behavioral characteristics, season, and chronic conditions. Results. Thirty-three percent of participants had 25(OH) D <20 ng/mL. Serum 25(OH) D was not associated with CES-D scores at baseline (p = .51); however, CES-D scores increased over time and were significantly associated with 25(OH) D at 2-year (p = .003) and 4-year follow-up (p < .001). Among 2,156 participants free of depression at the 1-year follow-up, the cumulative incidence of depression was 26.9%. Participants with 25(OH) D <20 ng/mL were at greater risk of developing depression (HR [95% CI]: 1.65 [1.23-2.22]) over 4 years of follow-up compared with those with 25(OH) D >= 30 ng/mL. Conclusion. Low 25(OH)D was independently associated with a greater increase in depressive symptom scores and incident depression in community-dwelling older adults. C1 [Williams, Julie A.; Sink, Kaycee M.; Atkinson, Hal H.; Kritchevsky, Stephen B.; Houston, Denise K.] Wake Forest Sch Med, Dept Internal Med Gerontol & Geriatr Med, Winston Salem, NC 27157 USA. [Tooze, Janet A.] Wake Forest Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Tylavsky, Frances A.] Univ Tennessee Hlth Sci, Dept Biostat & Epidemiol, Memphis, TN USA. [Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.] NIA, Baltimore, MD 21224 USA. RP Williams, JA (reprint author), Wake Forest Sch Med, Dept Internal Med Gerontol & Geriatr Med, Sticht Ctr Aging, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM juwillia@wakehealth.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU National Institutes of Health; National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01 AG028050, R01 AG029364]; National Institute of Nursing Research [R01 NR012459]; Wake Forest University Claude D. Pepper Older Americans Independence Center [P30 AG021332]; John A. Hartford Foundation FX This work was supported in part by the Intramural Research Program of the National Institutes of Health; National Institute on Aging; National Institute on Aging contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; National Institute on Aging grants R01 AG028050 and R01 AG029364; National Institute of Nursing Research grant R01 NR012459; and the Wake Forest University Claude D. Pepper Older Americans Independence Center (P30 AG021332). Additional support was provided by the John A. Hartford Foundation (to J.W.). NR 38 TC 3 Z9 3 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2015 VL 70 IS 6 BP 757 EP 763 DI 10.1093/gerona/glu184 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CM7MS UT WOS:000357878400014 PM 25326643 ER PT J AU Decker, B Parker, HG Dhawan, D Kwon, EM Karlins, E Davis, BW Ramos-Vara, JA Bonney, PL McNiel, EA Knapp, DW Ostrander, EA AF Decker, Brennan Parker, Heidi G. Dhawan, Deepika Kwon, Erika M. Karlins, Eric Davis, Brian W. Ramos-Vara, Jose A. Bonney, Patty L. McNiel, Elizabeth A. Knapp, Deborah W. Ostrander, Elaine A. TI Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer-Evidence for a Relevant Model System and Urine-Based Diagnostic Test SO MOLECULAR CANCER RESEARCH LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; RAF INHIBITORS; DOMESTIC DOG; LUNG-CANCER; B-RAF; GENOME; MELANOMA; GENE; VEMURAFENIB; ACTIVATION AB Targeted cancer therapies offer great clinical promise, but treatment resistance is common, and basic research aimed at overcoming this challenge is limited by reduced genomic and biologic complexity in artificially induced rodent tumors compared with their human counterparts. Animal models that more faithfully recapitulate genotype-specific human pathology could improve the predictive value of these investigations. Here, a newly identified animal model for oncogenic BRAF-driven cancers is described. With 20,000 new cases in the United States each year, canine invasive transitional cell carcinoma of the bladder (InvTCC) is a common, naturally occurring malignancy that shares significant histologic, biologic, and clinical phenotypes with human muscle invasive bladder cancer. In order to identify somatic drivers of canine InvTCC, the complete transcriptome for multiple tumors was determined by RNAseq. All tumors harbored a somatic mutation that is homologous to the human BRAF(V600E) mutation, and an identical mutation was present in 87% of 62 additional canine InvTCC tumors. The mutation was also detectable in the urine sediments of all dogs tested with mutation-positive tumors. Functional experiments suggest that, like human tumors, canine activating BRAF mutations potently stimulate the MAPK pathway. Cell lines with the mutation have elevated levels of phosphorylated MEK, compared with a line with wild-type BRAF. This effect can be diminished through application of the BRAF(V600E) inhibitor vemurafenib. These findings set the stage for canine InvTCC as a powerful system to evaluate BRAF-targeted therapies, as well as therapies designed to overcome resistance, which could enhance treatment of both human and canine cancers. (C) 2015 AACR. C1 [Decker, Brennan; Parker, Heidi G.; Kwon, Erika M.; Karlins, Eric; Davis, Brian W.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Decker, Brennan] Univ Cambridge, Cambridge, England. [Dhawan, Deepika; Bonney, Patty L.; Knapp, Deborah W.] Purdue Univ, Dept Vet Clin Sci, Purdue Comparat Oncol Program, W Lafayette, IN 47907 USA. [Ramos-Vara, Jose A.] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. [McNiel, Elizabeth A.] Tufts Univ, Cummings Sch Vet Med, North Grafton, MA USA. [Knapp, Deborah W.] Purdue Univ, Ctr Canc Res, W Lafayette, IN 47907 USA. RP Ostrander, EA (reprint author), NHGRI, NIH, 50 South Dr,Bldg 50,Room 5351, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Decker, Brennan/0000-0003-4516-7421; Ostrander, Elaine/0000-0001-6075-9738 FU Intramural Program of the National Human Genome Research Institute at NIH; AKC-Canine Health Foundation grants [754, 1336, 1577] FX This work was supported by the Intramural Program of the National Human Genome Research Institute at NIH. Additional support was received from the AKC-Canine Health Foundation grants 754, 1336, and 1577 (to E.A. Ostrander, H.G. Parker, and D.W. Knapp); and private donations made for bladder cancer research at Purdue University (to D.W. Knapp). NR 62 TC 7 Z9 7 U1 4 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD JUN PY 2015 VL 13 IS 6 BP 993 EP 1002 DI 10.1158/1541-7786.MCR-14-0689 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CM9WC UT WOS:000358059200004 PM 25767210 ER PT J AU Pigott, DM Golding, N Mylne, A Huang, Z Weiss, DJ Brady, OJ Kraemer, MUG Hay, SI AF Pigott, David M. Golding, Nick Mylne, Adrian Huang, Zhi Weiss, Daniel J. Brady, Oliver J. Kraemer, Moritz U. G. Hay, Simon I. TI Mapping the zoonotic niche of Marburg virus disease in Africa SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE Boosted regression trees; Filovirus; Marburg virus disease; Rousettus aegyptiacus; Species distribution models; Viral haemorrhagic fever ID SANS-FRONTIERES INTERVENTION; SPECIES DISTRIBUTION MODELS; HEMORRHAGIC-FEVER EPIDEMIC; EBOLA-VIRUS; RESERVOIR HOSTS; OUTBREAK; ANGOLA; UGANDA; UIGE; POPULATIONS AB Background: Marburg virus disease (MVD) describes a viral haemorrhagic fever responsible for a number of outbreaks across eastern and southern Africa. It is a zoonotic disease, with the Egyptian rousette (Rousettus aegyptiacus) identified as a reservoir host. Infection is suspected to result from contact between this reservoir and human populations, with occasional secondary human-to-human transmission. Methods: Index cases of previous human outbreaks were identified and reports of infection in animals recorded. These data were modelled within a species distribution modelling framework in order to generate a probabilistic surface of zoonotic transmission potential of MVD across sub-Saharan Africa. Results: Areas suitable for zoonotic transmission of MVD are predicted in 27 countries inhabited by 105 million people. Regions are suggested for exploratory surveys to better characterise the geographical distribution of the disease, as well as for directing efforts to communicate the risk of practices enhancing zoonotic contact. Conclusions: These maps can inform future contingency and preparedness strategies for MVD control, especially where secondary transmission is a risk. Coupling this risk map with patient travel histories could be used to guide the differential diagnosis of highly transmissible pathogens, enabling more rapid response to outbreaks of haemorrhagic fever. C1 [Pigott, David M.; Golding, Nick; Mylne, Adrian; Huang, Zhi; Weiss, Daniel J.; Brady, Oliver J.; Kraemer, Moritz U. G.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England. [Hay, Simon I.] Fogarty Int Ctr, NIH, Bethesda, MD USA. RP Pigott, DM (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford, England. EM david.pigott@zoo.ox.ac.uk RI Hay, Simon/F-8967-2015; OI Brady, Oliver/0000-0002-3235-2129; Hay, Simon/0000-0002-0611-7272; Pigott, David/0000-0002-6731-4034; Golding, Nick/0000-0001-8916-5570 FU Department of Zoology at the University of Oxford; Bill & Melinda Gates Foundation [OPP1053338, OPP1106023, OPP1068048, OPP1093011]; BBSRC; German Academic Exchange Service (DAAD); Wellcome Trust [095066]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX DMP is funded by a Sir Richard Southwood Graduate Scholarship from the Department of Zoology at the University of Oxford; NG is funded by a grant from the Bill & Melinda Gates Foundation [OPP1053338]; ZH is funded by the Bill & Melinda Gates Foundation [OPP1106023]; DJW is funded by the Bill & Melinda Gates Foundation [OPP1068048]; OJB is funded by a BBSRC studentship; MUGK is funded by the German Academic Exchange Service (DAAD) through a graduate scholarship; SIH is funded by a Senior Research Fellowship from the Wellcome Trust [095066] that also supports AM and a grant from the Bill & Melinda Gates Foundation [OPP1093011]. SIH would also like to acknowledge funding support from the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health. NR 64 TC 17 Z9 17 U1 5 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0035-9203 EI 1878-3503 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD JUN PY 2015 VL 109 IS 6 BP 366 EP 378 DI 10.1093/trstmh/trv024 PG 13 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CM9HZ UT WOS:000358020400004 PM 25820266 ER PT J AU Rausch, JW Le Grice, SFJ AF Rausch, Jason W. Le Grice, Stuart F. J. TI HIV Rev Assembly on the Rev Response Element (RRE): A Structural Perspective SO VIRUSES-BASEL LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; SELECTIVE 2'-HYDROXYL ACYLATION; BIOACTIVE SMALL MOLECULES; GENE-EXPRESSION REQUIRES; RNA MAJOR GROOVE; SECONDARY STRUCTURE; MESSENGER-RNA; BINDING-SITE; TRANS-ACTIVATOR; TARGET SEQUENCE AB HIV-1 Rev is an ~13 kD accessory protein expressed during the early stage of virus replication. After translation, Rev enters the nucleus and binds the Rev response element (RRE), a ~350 nucleotide, highly structured element embedded in the env gene in unspliced and singly spliced viral RNA transcripts. Rev-RNA assemblies subsequently recruit Crm1 and other cellular proteins to form larger complexes that are exported from the nucleus. Once in the cytoplasm, the complexes dissociate and unspliced and singly-spliced viral RNAs are packaged into nascent virions or translated into viral structural proteins and enzymes, respectively. Rev binding to the RRE is a complex process, as multiple copies of the protein assemble on the RNA in a coordinated fashion via a series of Rev-Rev and Rev-RNA interactions. Our understanding of the nature of these interactions has been greatly advanced by recent studies using X-ray crystallography, small angle X-ray scattering (SAXS) and single particle electron microscopy as well as biochemical and genetic methodologies. These advances are discussed in detail in this review, along with perspectives on development of antiviral therapies targeting the HIV-1 RRE. C1 [Rausch, Jason W.; Le Grice, Stuart F. J.] Frederick Natl Lab Canc Res, Reverse Transcriptase Biochem Sect, Basic Res Program, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), Frederick Natl Lab Canc Res, Reverse Transcriptase Biochem Sect, Basic Res Program, Frederick, MD 21702 USA. EM rauschj@mail.nih.gov; legrices@mail.nih.gov FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services, USA FX Stuart F. J. Le Grice and Jason W. Rausch were supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, USA. NR 82 TC 12 Z9 12 U1 2 U2 13 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD JUN PY 2015 VL 7 IS 6 BP 3053 EP 3075 DI 10.3390/v7062760 PG 23 WC Virology SC Virology GA CM6LC UT WOS:000357799000016 PM 26075509 ER PT J AU Fiandaca, MS Kapogiannis, D Mapstone, M Boxer, A Eitan, E Schwartz, JB Abner, EL Petersen, RC Federoff, HJ Miller, BL Goetzl, EJ AF Fiandaca, Massimo S. Kapogiannis, Dimitrios Mapstone, Mark Boxer, Adam Eitan, Erez Schwartz, Janice B. Abner, Erin L. Petersen, Ronald C. Federoff, Howard J. Miller, Bruce L. Goetzl, Edward J. TI Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study SO ALZHEIMERS & DEMENTIA LA English DT Article DE Preclinical AD; Neural exosomes; P-Tau; A beta 1-42; Biomarkers ID NEURODEGENERATIVE DISEASES; COGNITIVE IMPAIRMENT; MOUSE MODEL; ASSOCIATION; COHORT; TAU; BIOMARKERS; DIAGNOSIS; CRITERIA; DECLINE AB Background: Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD. Methods: Blood exosomes obtained at one time-point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two time-points from others (n = 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by enzyme-linked immunosorbent assays. Results: Mean exosomal levels of total tau, P-T181-tau, P-S396-tau, and amyloid beta 1-42 (A beta 1-42) for AD and levels of P-T181-tau and A beta 1-42 for FTD were significantly higher than for case-controls. Step-wise discriminant modeling incorporated P-T181-tau, P-S396-tau, and A beta 1-42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P-T181-tau, and A beta 1-42 were significantly higher than for controls both 1 to 10 years before and when diagnosed with AD. Conclusions: Levels of P-S396-tau, P-T181-tau, and A beta 1-42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Fiandaca, Massimo S.; Federoff, Howard J.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. [Fiandaca, Massimo S.; Federoff, Howard J.] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. [Kapogiannis, Dimitrios; Eitan, Erez] NIA, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Mapstone, Mark] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Boxer, Adam; Miller, Bruce L.] UCSF Med Ctr, Memory & Aging Ctr, Dept Neurol, San Francisco, CA USA. [Schwartz, Janice B.; Goetzl, Edward J.] UCSF Med Ctr, Dept Med, San Francisco, CA 94143 USA. [Schwartz, Janice B.; Goetzl, Edward J.] Jewish Home San Francisco, San Francisco, CA USA. [Abner, Erin L.] Univ Kentucky, Dept Neurol, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. RP Goetzl, EJ (reprint author), UCSF Med Ctr, Dept Med, San Francisco, CA 94143 USA. EM edward.goetzl@ucsf.edu FU Intramural Research Program of the National Institute on Aging (NIA); NIA from the National Institutes of Health (NIH) [RO1AG030753]; UK ADC [P30 AG028383]; Nanosomix, Inc. FX Intramural Research Program of the National Institute on Aging (NIA; DK, EE), NIA RO1AG030753 from the National Institutes of Health (NIH; HJF), UK ADC P30 AG028383(ELA), and an unrestricted grant for technological development from Nanosomix, Inc. (EJG). NR 28 TC 50 Z9 50 U1 8 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2015 VL 11 IS 6 BP 600 EP 607 DI 10.1016/j.jalz.2014.06.008 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CL8NR UT WOS:000357231900003 PM 25130657 ER PT J AU Jones, L Lambert, JC Wang, LS Choi, SH Harold, D Vedernikov, A Escott-Price, V Stone, T Richards, A Bellenguez, C Ibrahim-Verbaas, CA Naj, AC Sims, R Gerrish, A Jun, G DeStefano, AL Bis, JC Beecham, GW Grenier-Boley, B Russo, G Thornton-Wells, TA Jones, N Smith, AV Chouraki, V Thomas, C Ikram, MA Zelenika, D Vardarajan, BN Kamatani, Y Lin, CF Schmidt, H Kunkle, BW Dunstan, ML Ruiz, A Bihoreau, MT Reitz, C Pasquier, F Hollingworth, P Hanon, O Fitzpatrick, AL Buxbaum, JD Campion, D Crane, PK Becker, T Gudnason, V Cruchaga, C Craig, D Amin, N Berr, C Lopez, OL De Jager, PL Deramecourt, V Johnston, JA Evans, D Lovestone, S Letteneur, L Kornhuber, J Tarraga, L Rubinsztein, DC Eiriksdottir, G Sleegers, K Goate, AM Fievet, N Huentelman, MJ Gill, M Emilsson, V Brown, K Kamboh, MI Keller, L Barberger-Gateau, P McGuinness, B Larson, EB Myers, AJ Dufouil, C Todd, S Wallon, D Love, S Kehoe, P Rogaeva, E Gallacher, J St George-Hyslop, P Clarimon, J Lleo, A Bayer, A Tsuang, DW Yu, L Tsolaki, M Bossu, P Spalletta, G Proitsi, P Collinge, J Sorbi, S Garcia, FS Fox, N Hardy, J Naranjo, MCD Razquin, C Bosco, P Clarke, R Brayne, C Galimberti, D Mancuso, M Moebus, S Mecocci, P del Zompo, M Maier, W Hampel, H Pilotto, A Bullido, M Panza, F Caffarra, P Nacmias, B Gilbert, JR Mayhaus, M Jessen, F Dichgans, M Lannfelt, L Hakon, H Pichler, S Carrasquillo, MM Ingelsson, M Beekly, D Alavarez, V Zou, FG Valladares, O Younkin, SG Coto, E Hamilton-Nelson, KL Mateo, I Owen, MJ Faber, KM Jonsson, PV Combarros, O O'Donovan, MC Cantwell, LB Soininen, H Blacker, D Mead, S Mosley, TH Bennett, DA Harris, TB Fratiglioni, L Holmes, C de Bruijn, RFAG Passmore, P Montine, TJ Bettens, K Rotter, JI Brice, A Morgan, K Foroud, TM Kukull, WA Hannequin, D Powell, JF Nails, MA Ritchie, K Lunetta, KL Kauwe, JSK Boerwinkle, E Riemenschneider, M Boada, M Hiltunen, M Martin, ER Pastor, P Schmidt, R Rujescu, D Dartigues, JF Mayeux, R Tzourio, C Hofman, A Nothen, MM Graff, C Psaty, BM Haines, JL Lathrop, M Pericak-Vance, MA Launer, LJ Farrer, LA van Duijn, CM Van Broeckhoven, C Ramirez, A Schellenberg, GD Seshadri, S Amouyel, P Williams, J Holmans, PA AF Jones, Lesley Lambert, Jean-Charles Wang, Li-San Choi, Seung-Hoan Harold, Denise Vedernikov, Alexey Escott-Price, Valentina Stone, Timothy Richards, Alexander Bellenguez, Celine Ibrahim-Verbaas, Carla A. Naj, Adam C. Sims, Rebecca Gerrish, Amy Jun, Gyungah DeStefano, Anita L. Bis, Joshua C. Beecham, Gary W. Grenier-Boley, Benjamin Russo, Giancarlo Thornton-Wells, Tricia A. Jones, Nicola Smith, Albert V. Chouraki, Vincent Thomas, Charlene Ikram, M. Arfan Zelenika, Diana Vardarajan, Badri N. Kamatani, Yoichiro Lin, Chiao-Feng Schmidt, Helena Kunkle, Brian W. Dunstan, Melanie L. Ruiz, Agustin Bihoreau, Marie-Therese Reitz, Christiane Pasquier, Florence Hollingworth, Paul Hanon, Olivier Fitzpatrick, Annette L. Buxbaum, Joseph D. Campion, Dominique Crane, Paul K. Becker, Tim Gudnason, Vilmundur Cruchaga, Carlos Craig, David Amin, Najaf Berr, Claudine Lopez, Oscar L. De Jager, Philip L. Deramecourt, Vincent Johnston, Janet A. Evans, Denis Lovestone, Simon Letteneur, Luc Kornhuber, Johanes Tarraga, Lluis Rubinsztein, David C. Eiriksdottir, Gudny Sleegers, Kristel Goate, Alison M. Fievet, Nathalie Huentelman, Matthew J. Gill, Michael Emilsson, Valur Brown, Kristelle Kamboh, M. Ilyas Keller, Lina Barberger-Gateau, Pascale McGuinness, Bernadette Larson, Eric B. Myers, Amanda J. Dufouil, Carole Todd, Stephen Wallon, David Love, Seth Kehoe, Pat Rogaeva, Ekaterina Gallacher, John St George-Hyslop, Peter Clarimon, Jordi Lleo, Alberti Bayer, Anthony Tsuang, Debby W. Yu, Lei Tsolaki, Magda Bossu, Paola Spalletta, Gianfranco Proitsi, Petra Collinge, John Sorbi, Sandro Garcia, Fiorentino Sanchez Fox, Nick Hardy, John Deniz Naranjo, Maria Candida Razquin, Cristina Bosco, Paola Clarke, Robert Brayne, Carol Galimberti, Daniela Mancuso, Michelangelo Moebus, Susanne Mecocci, Patrizia del Zompo, Maria Maier, Wolfgang Hampel, Harald Pilotto, Alberto Bullido, Maria Panza, Francesco Caffarra, Paolo Nacmias, Benedetta Gilbert, John R. Mayhaus, Manuel Jessen, Frank Dichgans, Martin Lannfelt, Lars Hakonarson, Hakon Pichler, Sabrina Carrasquillo, Minerva M. Ingelsson, Martin Beekly, Duane Alavarez, Victoria Zou, Fanggeng Valladares, Otto Younkin, Steven G. Coto, Eliecer Hamilton-Nelson, Kara L. Mateo, Ignacio Owen, Michael J. Faber, Kelley M. Jonsson, Palmi V. Combarros, Onofre O'Donovan, Michael C. Cantwell, Laura B. Soininen, Hilkka Blacker, Deborah Mead, Simon Mosley, Thomas H., Jr. Bennett, David A. Harris, Tamara B. Fratiglioni, Laura Holmes, Clive de Bruijn, Renee F. A. G. Passmore, Peter Montine, Thomas J. Bettens, Karolien Rotter, Jerome I. Brice, Alexis Morgan, Kevin Foroud, Tatiana M. Kukull, Walter A. Hannequin, Didier Powell, John F. Nails, Michael A. Ritchie, Karen Lunetta, Kathryn L. Kauwe, John S. K. Boerwinkle, Eric Riemenschneider, Matthias Boada, Merce Hiltunen, Mikko Martin, Eden R. Pastor, Pau Schmidt, Reinhold Rujescu, Dan Dartigues, Jean-Francois Mayeux, Richard Tzourio, Christophe Hofman, Albert Noethen, Markus M. Graff, Caroline Psaty, Bruce M. Haines, Jonathan L. Lathrop, Mark Pericak-Vance, Margaret A. Launer, Lenore J. Farrer, Lindsay A. van Duijn, Cornelia M. Van Broeckhoven, Christine Ramirez, Alfredo Schellenberg, Gerard D. Seshadri, Sudha Amouyel, Philippe Williams, Julie Holmans, Peter A. CA Int Genomics Alzheimer's Dis Conso MRC CFAS TI Convergent genetic and expression data implicate immunity in Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Dementia; Neurodegeneration; Immune response; Endocytosis; Cholesterol metabolism; Ubiquitination; Pathway analysis; ALIGATOR; Weighted gene co-expression network analysis ID GENOME-WIDE ASSOCIATION; NETWORK ANALYSIS; UNITED-STATES; PREVALENCE; VARIANTS; POPULATION; BRAIN; LISTS AB Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. (C) 2015 Published by Elsevier Inc. on behalf of The Alzheimer's Association. C1 [Jones, Lesley; Vedernikov, Alexey; Escott-Price, Valentina; Stone, Timothy; Richards, Alexander; Sims, Rebecca; Gerrish, Amy; Jones, Nicola; Thomas, Charlene; Dunstan, Melanie L.; Hollingworth, Paul; Owen, Michael J.; O'Donovan, Michael C.; Williams, Julie; Holmans, Peter A.] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales. [Lambert, Jean-Charles; Bellenguez, Celine; Grenier-Boley, Benjamin; Chouraki, Vincent; Deramecourt, Vincent; Fievet, Nathalie; Amouyel, Philippe] Inserm U744, F-59000 Lille, France. [Lambert, Jean-Charles; Bellenguez, Celine; Grenier-Boley, Benjamin; Chouraki, Vincent; Pasquier, Florence; Amouyel, Philippe] Univ Lille 2, F-59000 Lille, France. [Lambert, Jean-Charles; Bellenguez, Celine; Grenier-Boley, Benjamin; Chouraki, Vincent; Fievet, Nathalie; Amouyel, Philippe] Inst Pasteur, F-59000 Lille, France. [Ibrahim-Verbaas, Carla A.] Erasmus MC Univ Med Ctr, Dept Epidemiol Clin Genet & Neurol, NL-3015 CE Rotterdam, Netherlands. [Naj, Adam C.; Beecham, Gary W.; Kunkle, Brian W.; Gilbert, John R.; Hamilton-Nelson, Kara L.; Martin, Eden R.; Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Coral Gables, FL 33124 USA. [Jun, Gyungah; Vardarajan, Badri N.; Farrer, Lindsay A.] Boston Univ Sch Med, Dept Med Biomed Genet, Boston, MA 02218 USA. [Jun, Gyungah; Farrer, Lindsay A.] Boston Univ Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. [Choi, Seung-Hoan; Jun, Gyungah; DeStefano, Anita L.; Lunetta, Kathryn L.; Farrer, Lindsay A.] Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Bis, Joshua C.; Fitzpatrick, Annette L.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Beecham, Gary W.; Martin, Eden R.; Pericak-Vance, Margaret A.] Univ Miami, Dr John T Macdonald Fdn Dept Human Genet, Miami, FL 33124 USA. [Russo, Giancarlo; Amouyel, Philippe] Funct Genom Ctr, CH-8038 Zurich, Switzerland. [Thornton-Wells, Tricia A.; Haines, Jonathan L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. [Smith, Albert V.; Gudnason, Vilmundur; Emilsson, Valur] Univ Iceland, Fac Pharmaceut Sci, IS-5254000 Reykjavik, Iceland. [Smith, Albert V.; Gudnason, Vilmundur; Eiriksdottir, Gudny; Emilsson, Valur] Iceland Heart Assoc, IS-5254000 Kopavogur, Iceland. [Ikram, M. Arfan; Hofman, Albert] Erasmus MC Univ Med Ctr, Dept Epidemiol, NL-3015 CE Rotterdam, Netherlands. [Ikram, M. Arfan; Hofman, Albert] Erasmus MC Univ Med Ctr, Dept Neurol, NL-3015 CE Rotterdam, Netherlands. [Ikram, M. Arfan; Hofman, Albert] Erasmus MC Univ Med Ctr, Dept Radiol, NL-3015 CE Rotterdam, Netherlands. [Ikram, M. Arfan; Hofman, Albert] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Zelenika, Diana; Bihoreau, Marie-Therese; Lathrop, Mark] CEA, Inst Genom, Ctr Natl Genotypage, F-91300 Evry, France. [Kamatani, Yoichiro; Lathrop, Mark] Fdn Jean Dausset CEPH, F-75010 Paris, France. [Wang, Li-San; Lin, Chiao-Feng; Valladares, Otto; Cantwell, Laura B.; Schellenberg, Gerard D.] Univ Penn Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, A-8010 Graz, Austria. [Ruiz, Agustin; Tarraga, Lluis] Fundacio ACE, Memory Clin, Inst Catala Neurociencies Aplicades, Barcelona 8029, Spain. [Reitz, Christiane; Mayeux, Richard] Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY 10027 USA. [Reitz, Christiane; Mayeux, Richard] Columbia Univ, Dept Neurol, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [Pasquier, Florence; Deramecourt, Vincent; Amouyel, Philippe] CHRU Lille, F-59037 Lille, France. [Ramirez, Alfredo] Univ Bonn, Dept Psychiat & Psychotherapy, D-53113 Bonn, Germany. [Ramirez, Alfredo] Univ Bonn, Inst Human Genet, D-53113 Bonn, Germany. [Hanon, Olivier] Univ Paris 05, Fac Med, UMR Inserm 894, F-75014 Paris, France. [Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Fitzpatrick, Annette L.] Univ Washington, Dept Global Hlth, Seattle, WA 98101 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10027 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10027 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet, New York, NY 10027 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genom Sci, New York, NY 10027 USA. [Campion, Dominique; Wallon, David; Hannequin, Didier] Ctr Hosp Rouvray, Fac Med, INSERM U614, F-76000 Rouen, France. [Crane, Paul K.; Larson, Eric B.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Becker, Tim] Univ Bonn, German Ctr Neurodegenerat Dis DZNE, D-53113 Bonn, Germany. [Becker, Tim] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53113 Bonn, Germany. [Cruchaga, Carlos; Goate, Alison M.] Washington Univ Sch Med, Dept Psychiat, St Louis, MO USA. [Cruchaga, Carlos; Goate, Alison M.] Washington Univ Sch Med, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO USA. [Craig, David; Johnston, Janet A.; McGuinness, Bernadette; Todd, Stephen; Passmore, Peter] Queens Univ Belfast, Ageing Grp, Ctr Publ Hlth, Sch Med Dent & Biomed Sci, Belfast BT7 1NN, Antrim, North Ireland. [Amin, Najaf; van Duijn, Cornelia M.] Erasmus MC Univ Med Ctr, Dept Epidemiol, NL-3015 CE Rotterdam, Netherlands. [Berr, Claudine; Ritchie, Karen] Hop La Colombiere, INSERM U888, F-34000 Montpellier, France. [Lopez, Oscar L.] Univ Pittsburgh Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci, Dept Neurol & Psychiat, Boston, MA 02215 USA. [De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Boston, MA 02215 USA. [Evans, Denis] Rush Univ Med Ctr, Dept Internal Med, Rush Inst Hlth Aging, Chicago, IL 60612 USA. [Lovestone, Simon; Proitsi, Petra; Powell, John F.] Kings Coll London, Inst Psychiat, Dept Neurosci, London SE5, England. [Letteneur, Luc; Barberger-Gateau, Pascale; Dufouil, Carole; Dartigues, Jean-Francois] Victor Segalen Univ, Inserm U897, F-33076 Bordeaux, France. [Kornhuber, Johanes] Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, Erlangen, Germany. [Rubinsztein, David C.; Kauwe, John S. K.] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 OXY, England. [Sleegers, Kristel; Bettens, Karolien; Van Broeckhoven, Christine] VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, B-2000 Antwerp, Belgium. [Sleegers, Kristel; Bettens, Karolien; Van Broeckhoven, Christine] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2000 Antwerp, Belgium. [Huentelman, Matthew J.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ 85004 USA. [Gill, Michael] St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland. [Gill, Michael] Univ Ireland Trinity Coll, Dublin 8, Ireland. [Brown, Kristelle; Morgan, Kevin] Univ Nottingham, Inst Genet, Queens Med Ctr, Nottingham NG7 2UH, England. [Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15213 USA. [Kamboh, M. Ilyas] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA 15213 USA. [Keller, Lina] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Aging Reasearch Ctr, S-17177 Stockholm, Sweden. [Keller, Lina] Stockholm Univ, S-17177 Stockholm, Sweden. [Larson, Eric B.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA 98195 USA. [Myers, Amanda J.] Univ Miami, Dept Psychiat & Behav Sci, Miller Sch Med, Miami, FL 33124 USA. [Love, Seth; Kehoe, Pat] Univ Bristol, Clin Neurosci, Bristol BS10 5NB, Avon, England. [Rogaeva, Ekaterina; St George-Hyslop, Peter] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5S 1A1, Canada. [Gallacher, John; Bayer, Anthony] Cardiff Univ, Inst Primary Care & Publ Hlth, Univ Wales Hosp, Cardiff CF14 4XN, S Glam, Wales. [St George-Hyslop, Peter] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 1TN, England. [St George-Hyslop, Peter] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 1TN, England. [Clarimon, Jordi; Lleo, Alberti] Univ Autonoma Barcelona, Neurol Dept, IIB St Pau, St Pau Hosp, Barcelona 08026, Spain. [Clarimon, Jordi; Lleo, Alberti] Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Barcelona, Spain. [Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Yu, Lei; Bennett, David A.] Rush Univ Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Tsolaki, Magda] Aristotle Univ Thessaloniki, Thessaloniki 54621, Greece. [Bossu, Paola; Spalletta, Gianfranco] Fdn Santa Lucia, Clin & Behav Neurol, I-00142 Rome, Italy. [Collinge, John; Mead, Simon] UCL Inst Neurol, Dept Neurodegenerat Dis, MRC Prion Unit, London WC1N 3BG, England. [Nacmias, Benedetta] Univ Florence, Dept Neurol & Psychiat Sci, I-50121 Florence, Italy. [Sorbi, Sandro; Nacmias, Benedetta] Univ Florence, Ctr Ric Trasferimento & Alta Formaz DENOTHE, Florence, Italy. [Garcia, Fiorentino Sanchez; Deniz Naranjo, Maria Candida] Hosp Univ Dr Negrin, Dept Immunol, Las Palmas Gran Canaria 35012, Spain. [Fox, Nick] UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London WC1N 3BG, England. [Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Hardy, John] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England. [Bosco, Paola] IRCCS Assoc Oasi Maria SS, I-94018 Troina, Italy. [Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, OHAP, Oxford OX1 2JD, England. [Brayne, Carol; MRC CFAS] Univ Cambridge, Inst Publ Hlth, CFAS, Cambridge CB2 1TN, England. [Galimberti, Daniela] Univ Milan, Fdn Ca Granda, IRCCS Osped Policlin, I-20122 Milan, Italy. [Mancuso, Michelangelo] Univ Pisa, Neurol Clin, I-56126 Pisa, Italy. [Moebus, Susanne] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Urban Epidemiol, Univ Hosp Essen, D-45141 Essen, Germany. [Mecocci, Patrizia] Univ Perugia, Sect Gerontol & Geriatr, Dept Clin & Expt Med, I-06100 Perugia, Italy. [del Zompo, Maria] Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, I-09123 Cagliari, Italy. [Maier, Wolfgang; Jessen, Frank] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany. [Maier, Wolfgang; Jessen, Frank] German Ctr Neurodegenerat Dis DZNE, D-53113 Bonn, Germany. [Hampel, Harald] Univ Paris 06, Dept Neurol, Inst Memoire & Malad Alzheimer, Paris, France. [Pilotto, Alberto] IRCCS Casa Sollievo Sofferenza, Gerontol & Geriatr Res Lab, I-71013 San Giovanni Rotondo, FG, Italy. [Bullido, Maria] Ctr Biol Mol Severo Ochoa CSIC UAM, Madrid 28046, Spain. [Bullido, Maria] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain. [Bullido, Maria] Inst Invest Sanitaria Hosp la Paz IdIPaz, Madrid, Spain. [Panza, Francesco] Univ Bari, Ctr Aging Brain, Dept Geriatr, I-70121 Bari, Italy. [Caffarra, Paolo] Univ Parma, Dept Neurosci, I-43100 Parma, Italy. [Caffarra, Paolo] Ctr Cognit Disorders AUSL, Parma, Italy. [Gilbert, John R.] Univ Miami, Dr John T Macdonald Fdn Dept Human Genet, Miami, FL 33124 USA. [Mayhaus, Manuel] Univ Hosp, Dept Psychiat, D-66424 Saarland, Germany. [Lannfelt, Lars; Ingelsson, Martin] Uppsala Univ, Dept Publ Hlth Geriatr, S-75312 Uppsala, Sweden. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Carrasquillo, Minerva M.; Zou, Fanggeng; Younkin, Steven G.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Beekly, Duane] Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA 98195 USA. [Alavarez, Victoria; Coto, Eliecer] Genet Mol Huca Oviedo, Oviedo 33006, Spain. [Mateo, Ignacio; Combarros, Onofre] Univ Cantabria, Marques de Valdecilla Univ Hosp, Neurol Serv, E-39005 Santander, Spain. [Mateo, Ignacio; Combarros, Onofre] Univ Cantabria, Marques de Valdecilla Univ Hosp, CIBERNED, E-39005 Santander, Spain. [Mateo, Ignacio; Combarros, Onofre] IFIMAV, Santander 39005, Spain. [Faber, Kelley M.; Foroud, Tatiana M.] Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Jonsson, Palmi V.] Landspitali Univ Hosp, IS-5431000 Reykjavik, Iceland. [Soininen, Hilkka; Hiltunen, Mikko] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio 70211, Finland. [Soininen, Hilkka; Hiltunen, Mikko] Kuopio Univ Hosp, Dept Neurol, FIN-70211 Kuopio, Finland. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Farrer, Lindsay A.] Boston Univ Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Mississippi Med Ctr, Dept Geriatr Med, Jackson, MS 39216 USA. [Mosley, Thomas H., Jr.; Bennett, David A.] Rush Univ Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Harris, Tamara B.] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Fratiglioni, Laura] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Aging Reasearch Ctr, S-11418 Stockholm, Sweden. [Fratiglioni, Laura] Stockholm Univ, S-11418 Stockholm, Sweden. [Fratiglioni, Laura; Graff, Caroline; Launer, Lenore J.] Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Genet Unit, S-14186 Stockholm, Sweden. [Holmes, Clive] Univ Southampton, Sch Med, Div Clin Neurosci, Southampton SO17 1BJ, Hants, England. [de Bruijn, Renee F. A. G.] Erasmus MC Univ Med Ctr, Dept Neurol, NL-3015 CE Rotterdam, Netherlands. [de Bruijn, Renee F. A. G.] Erasmus MC Univ Med Ctr, Dept Epidemiol, NL-3015 CE Rotterdam, Netherlands. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Brice, Alexis] CRicm UMRS975, Paris, France. [Brice, Alexis] Hop La Pitie Salpetriere, AP HP, F-75013 Paris, France. [Kukull, Walter A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Nails, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Houston, TX 77030 USA. [Riemenschneider, Matthias] Univ Hosp, Dept Psychiat, Saarland 66424, Germany. [Boada, Merce] Fundacio ACE, Memory Clin, Inst Catala Neurociencies Aplicades, Barcelona 8029, Spain. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, A-8010 Graz, Austria. [Rujescu, Dan] Univ Munich, Dept Psychiat, D-80539 Munich, Germany. [Rujescu, Dan] Univ Halle, D-80336 Halle, Germany. [Dartigues, Jean-Francois] CHU Bordeaux, Ctr Memoire Ressources & Rech Bordeaux, Bordeaux, France. [Tzourio, Christophe] Victor Segalen Univ, Inserm U708, F-33076 Bordeaux, France. [Noethen, Markus M.] Univ Bonn, Inst Human Genet, Dept Genom, Life & Brain Ctr, D-53113 Bonn, Germany. [Noethen, Markus M.] German Ctr Neurodegenerat Dis DZNE, D-53113 Bonn, Germany. [Graff, Caroline] Karolinska Inst, Dept Neurobiol Care Sci & Soc, KIADRC, S-17177 Stockholm, Sweden. [Haines, Jonathan L.] Vanderbilt Univ, Vanderbilt Ctr Human Genet Res, Nashville, TN 37212 USA. [Lathrop, Mark] McGill Univ, Montreal, PQ, Canada. [Lathrop, Mark] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Farrer, Lindsay A.; Seshadri, Sudha] Boston Univ Sch Med, Dept Neurol, Boston, MA 02215 USA. [Razquin, Cristina; Pastor, Pau] Univ Navarra Sch Med, Div Neurosci, Ctr Appl Med Res, Neurogenet Lab, Pamplona 28023, Spain. [Pastor, Pau] Univ Navarra Sch Med, Dept Neurol, Univ Navarra Clin, Pamplona, Spain. [Pastor, Pau] Inst Salud Carlos III, CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain. [Dichgans, Martin] Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Dichgans, Martin] German Ctr Neurodegenerat Dis DZNE, D-80336 Munich, Germany. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Harold, Denise] St James Hosp, Neuropsychiat Genet Grp, Dept Psychiat, Trinity Ctr Hlth Sci, Dublin 8, Ireland. RP Williams, J (reprint author), Cardiff Univ, Inst Psychol Med & Clin Neurosci, Hadyn Ellis Bldg,Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales. EM philippe.amouyel@pasteur-lille.fr; williamsj@cardiff.ac.uk RI Hardy, John/C-2451-2009; Gudnason, Vilmundur/K-6885-2015; Lambert, jean-charles/A-9553-2014; Smith, Albert/K-5150-2015; Ritchie, Karen/G-3571-2013; Caffarra, Paolo/K-6567-2016; Tsuang, Debby/L-7234-2016; Tzourio, christophe/B-4015-2009; Bosso, Paola/E-4832-2014; Kamatani, Yoichiro/N-5513-2015; Pastor, Pau/C-9834-2009; Bullido, Maria/C-8509-2014; OI Gudnason, Vilmundur/0000-0001-5696-0084; Lambert, jean-charles/0000-0003-0829-7817; Smith, Albert/0000-0003-1942-5845; Caffarra, Paolo/0000-0003-2246-5223; Tsuang, Debby/0000-0002-4716-1894; Tzourio, christophe/0000-0002-6517-2984; Bosso, Paola/0000-0002-1432-0078; Pastor, Pau/0000-0002-7493-8777; Bullido, Maria/0000-0002-6477-1117; Todd, Stephen/0000-0002-2312-9195; Gill, Michael/0000-0003-0206-5337; Escott-Price, Valentina/0000-0003-1784-5483; Harold, Denise/0000-0001-5195-0143; Holmans, Peter/0000-0003-0870-9412; Buxbaum, Joseph/0000-0001-8898-8313; Panza, Francesco/0000-0002-7220-0656; Nothen, Markus/0000-0002-8770-2464; Denning, Nicola/0000-0001-8467-7382; Bayer, Antony/0000-0002-7514-248X; Farrer, Lindsay/0000-0001-5533-4225; Seshadri, Sudha/0000-0001-6135-2622; galimberti, daniela/0000-0002-9284-5953; Kukull, Walter/0000-0001-8761-9014; NACMIAS, Benedetta/0000-0001-9338-9040; sorbi, sandro/0000-0002-0380-6670; Kamboh, M. Ilyas/0000-0002-3453-1438 FU Wellcome Trust; Medical Research Council; Alzheimer's Research UK; Welsh Assembly Government; National Institutes of Health, National Institute on Aging (NIH-NIA); Erasmus Medical Center; Erasmus University; French National Foundation on Alzheimer's Disease and Related Disorders; Centre National de Genotypage; Institut Pasteur de Lille; Inserm; FRC (Fondation pour la Recherche sur le Cerveau); Rotary; LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease); Alzheimer's Association FX This work was made possible by the generous participation of the control subjects, the patients, and their families. GERAD was supported by the Wellcome Trust, Medical Research Council, Alzheimer's Research UK, and the Welsh Assembly Government. ADGC and CHARGE were supported by the National Institutes of Health, National Institute on Aging (NIH-NIA). CHARGE was also supported by Erasmus Medical Center and Erasmus University. IGAP was funded by the French National Foundation on Alzheimer's Disease and Related Disorders, the Centre National de Genotypage and the Institut Pasteur de Lille, Inserm, FRC (Fondation pour la Recherche sur le Cerveau), and Rotary. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease). The French National Foundation on Alzheimer's Disease and Related Disorders and the Alzheimer's Association provided support for I-GAP meetings, communication and some funds to each consortium to support analyses. NR 36 TC 20 Z9 20 U1 7 U2 37 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2015 VL 11 IS 6 BP 658 EP 671 DI 10.1016/j.jalz.2014.05.1757 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA CL8NR UT WOS:000357231900008 ER PT J AU Snyder, HM Corriveau, RA Craft, S Faber, JE Greenberg, SM Knopman, D Lamb, BT Montine, TJ Nedergaard, M Schaffer, CB Schneider, JA Wellington, C Wilcock, DM Zipfel, GJ Zlokovic, B Bain, LJ Bosetti, F Galis, ZS Koroshetz, W Carrillo, MC AF Snyder, Heather M. Corriveau, Roderick A. Craft, Suzanne Faber, James E. Greenberg, Steven M. Knopman, David Lamb, Bruce T. Montine, Thomas J. Nedergaard, Maiken Schaffer, Chris B. Schneider, Julie A. Wellington, Cheryl Wilcock, Donna M. Zipfel, Gregory J. Zlokovic, Berislav Bain, Lisa J. Bosetti, Francesca Galis, Zorina S. Koroshetz, Walter Carrillo, Maria C. TI Vascular contributions to cognitive impairment and dementia including Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Review DE Alzheimer's disease; Dementia; Biomarkers; Animal models; Vascular dementia; Small vessel disease ID CEREBRAL AMYLOID ANGIOPATHY; HIGH-DENSITY-LIPOPROTEIN; BLOOD-BRAIN-BARRIER; NATIVE COLLATERAL CIRCULATION; CARDIOVASCULAR RISK-FACTORS; ISCHEMIC-STROKE; MOUSE MODEL; A-BETA; CEREBROVASCULAR INTEGRITY; PRECURSOR PROTEIN AB Scientific evidence continues to demonstrate the linkage of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease. In December, 2013, the Alzheimer's Association, with scientific input from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung and Blood Institute from the National Institutes of Health, convened scientific experts to discuss the research gaps in our understanding of how vascular factors contribute to Alzheimer's disease and related dementia. This manuscript summarizes the meeting and the resultant discussion, including an outline of next steps needed to move this area of research forward. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Snyder, Heather M.; Carrillo, Maria C.] Alzheimers Assoc, Med & Sci Relat, Chicago, IL 60631 USA. [Corriveau, Roderick A.; Bosetti, Francesca; Koroshetz, Walter] NINDS, NIH, Bethesda, MD 20892 USA. [Craft, Suzanne] Wake Forest Univ Sch Med, Dept Gerontol & Geriatr Med, Winston Salem, NC USA. [Faber, James E.] Univ North Carolina Sch Med, Dept Cell Biol & Physiol, Chapel Hill, NC USA. [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Greenberg, Steven M.] Harvard Univ, Sch Med, Boston, MA USA. [Knopman, David] Mayo Clin, Dept Neurol, Rochester, MN USA. [Lamb, Bruce T.] Cleveland Clin, Dept Neurosci, Cleveland, OH 44106 USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Nedergaard, Maiken] Univ Rochester Med Ctr, Div Glial Dis & Therapeut, Rochester, NY USA. [Schaffer, Chris B.] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. [Schneider, Julie A.] Rush Univ Med Ctr, Dept Pathol, Chicago, IL USA. [Schneider, Julie A.] Rush Univ Med Ctr, Dept Neurol Sci, Chicago, IL USA. [Wellington, Cheryl] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Wilcock, Donna M.] Univ Kentucky, Dept Physiol, Lexington, KY USA. [Zipfel, Gregory J.] Washington Univ, Dept Neurol Surg, St Louis, MO USA. [Zipfel, Gregory J.] Washington Univ, Dept Neurol, St Louis, MO USA. [Zlokovic, Berislav] Univ So Calif, Dept Physiol, Los Angeles, CA USA. [Galis, Zorina S.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Snyder, HM (reprint author), Alzheimers Assoc, Med & Sci Relat, Chicago, IL 60631 USA. EM hsnyder@alz.org RI Schaffer, Chris/A-7409-2008; Wilcock, Donna/J-7517-2016 OI Schaffer, Chris/0000-0002-7800-9596; FU NIA NIH HHS [R01 AG048769]; NIDCR NIH HHS [R01 DE022743]; NINDS NIH HHS [R01 NS078167, R01 NS078304, R01 NS079637] NR 80 TC 64 Z9 64 U1 17 U2 53 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2015 VL 11 IS 6 BP 710 EP 717 DI 10.1016/j.jalz.2014.10.008 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CL8NR UT WOS:000357231900013 PM 25510382 ER PT J AU Hadley, D Hagopian, W Liu, E She, JX Simell, O Akolkar, B Ziegler, AG Rewers, M Krischer, JP Chen, WM Onengut-Gumuscu, S Bugawan, TL Rich, SS Erlich, H Agardh, D AF Hadley, David Hagopian, William Liu, Edwin She, Jin-Xiong Simell, Olli Akolkar, Beena Ziegler, Anette-G. Rewers, Marian Krischer, Jeffrey P. Chen, Wei-Min Onengut-Gumuscu, Suna Bugawan, Teodorica L. Rich, Stephen S. Erlich, Henry Agardh, Daniel CA TEDDY Study Grp TI HLA-DPB1(star)04:01 Protects Genetically Susceptible Children from Celiac Disease Autoimmunity in the TEDDY Study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HLA-DQ; TISSUE TRANSGLUTAMINASE; GENE DOSAGE; CLASS-II; DP; ASSOCIATION; HAPLOTYPE; RISK AB OBJECTIVES : Tissue transglutaminase autoantibodies (tTGAs) represent the first evidence of celiac disease (CD) development. Associations of HLA-DR3-DQA1(star)05:01-DQB1(star)02:01 (i.e., DR3-DQ2) and, to a lesser extent, DR4-DQA1(star)03:01-DQB1(star)03:02 (i.e., DR4-DQ8) with the risk of CD differ by country, consistent with additional genetic heterogeneity that further refines risk. Therefore, we examined human leukocyte antigen (HLA) factors other than DR3-DQ2 for their contribution to developing tTGAs. METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 infants at an increased HLA-DR-DQ risk for type 1 diabetes and CD into a 15-year prospective surveillance follow-up. Of those followed up, 21% (n=1,813) carried DR3-DQ2/DR3-DQ2, 39% (n=3,359) carried DR3-DQ2/DR4-DQ8, 20% (n=1701) carried DR4-DQ8/DR4-DQ8, and 17% (n=1,493) carried DR4-DQ8/DQ4. Within TEDDY, a nested case-control design of 248 children with CD autoimmunity (CDA) and 248 matched control children were genotyped for HLA-B, -DRB3, -DRB4, -DPA1, and -DPB1 genes, and the entire cohort was genotyped for single-nucleotide polymorphisms (SNPs) using the Illumina ImmunoChip. CDA was defined as a positive tTGA test at two consecutive clinic visits, whereas matching in those with no evidence of tTGAs was based on the presence of HLA-DQ2, country, and sex. RESULTS: After adjustment for DR3-DQ2 and restriction to allele frequency (AF) >= 5%, HLA-DPB1(star)04:01 was inversely associated with CDA by conditional logistic regression (AF=44%, odds ratio=0.71, 95% confidence interval (CI)=0.53-0.96, P=0.025). This association of time to CDA and HLA-DPB1(star)04: 01 was replicated with statistical significance in the remainder of the cohort using imputation for specific HLA alleles based on SNP genotyping (hazard ratio=0.84, 95% CI=0.73-0.96, P=0.013). CONCLUSIONS: HLA-DPB1(star)04:01 may reduce the risk of tTGAs, an early marker of CD, among DR3-DQ2 children, confirming that additional variants in the HLA region influence the risk for CDA. C1 [Hadley, David] Univ London, Div Populat Hlth Sci & Educ, London SW17 0RE, England. [Hadley, David] TransMed Syst, Pleasanton, CA USA. [Hagopian, William] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [Liu, Edwin; Rewers, Marian] Childrens Hosp Colorado, Digest Hlth Inst, Aurora, CO USA. [Liu, Edwin] Univ Colorado Denver, Barbara Davis Ctr, Aurora, CO USA. [She, Jin-Xiong] Georgia Regents Univ, Ctr Biotechnol & Genom Med, Augusta, GA USA. [Simell, Olli] Univ Turku, Dept Pediat, Turku, Finland. [Akolkar, Beena] NIDDK, DDEMD, Bethesda, MD 20892 USA. [Ziegler, Anette-G.] Helmholtz Zentrum Munchen, Diabet Res Inst, Oberschleissheim, Germany. [Ziegler, Anette-G.] Tech Univ Munich, Klinikum Rechts Isar, D-80290 Munich, Germany. [Ziegler, Anette-G.] Forschergrp Diabet eV, Neuherberg, Germany. [Krischer, Jeffrey P.; Agardh, Daniel] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Chen, Wei-Min; Onengut-Gumuscu, Suna; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Bugawan, Teodorica L.] Roche Mol Syst, Dept Human Genet, Alameda, CA USA. [Erlich, Henry] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Agardh, Daniel] Lund Univ, Dept Clin Sci, Malmo, Sweden. RP Hadley, D (reprint author), Univ London, Div Populat Hlth Sci & Educ, London SW17 0RE, England. EM dhadley@sgul.ac.uk FU National Institute of Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Disease (NIAID); National Institute of Environmental Health Sciences (NIEHS); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation (JDRF); Centers for Disease Control and Prevention (CDC); Department of Health and Human Services (DHHS) FX National Institute of Health (NIH), Department of Health and Human Services (DHHS), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Disease (NIAID), National Institute of Environmental Health Sciences (NIEHS), National Institute of Child Health and Human Development (NICHD), Juvenile Diabetes Research Foundation (JDRF), Centers for Disease Control and Prevention (CDC). NR 27 TC 6 Z9 6 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 2015 VL 110 IS 6 BP 915 EP 920 DI 10.1038/ajg.2015.150 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CL6MS UT WOS:000357081800021 PM 26010309 ER PT J AU Hahn, KJ Ho, N Yockey, L Kreuzberg, S Daub, J Rump, A Marciano, BE Quezado, M Malech, HL Holland, SM Heller, T Zerbe, CS AF Hahn, Katherine J. Ho, Nancy Yockey, Lynne Kreuzberg, Samantha Daub, Janine Rump, Amy Marciano, Beatriz E. Quezado, Martha Malech, Harry L. Holland, Steven M. Heller, Theo Zerbe, Christa S. TI Treatment With Anakinra, a Recombinant IL-1 Receptor Antagonist, Unlikely to Induce Lasting Remission in Patients With CGD Colitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID CHRONIC GRANULOMATOUS-DISEASE; BLOCKADE C1 [Hahn, Katherine J.] Medstar Georgetown Univ Hosp, Dept Internal Med, Washington, DC 20007 USA. [Ho, Nancy; Kreuzberg, Samantha; Heller, Theo] NIDDK, NIH, Bethesda, MD 20892 USA. [Yockey, Lynne; Daub, Janine; Rump, Amy; Marciano, Beatriz E.; Holland, Steven M.; Zerbe, Christa S.] NIAID, LCID, NIH, Bethesda, MD 20892 USA. [Quezado, Martha] NCI, NIH, Bethesda, MD 20892 USA. [Malech, Harry L.] NIH, Host Def Lab, Bethesda, MD 20892 USA. RP Hahn, KJ (reprint author), Medstar Georgetown Univ Hosp, Dept Internal Med, 3800 Resevoir Rd NW,PHC Floor 5, Washington, DC 20007 USA. EM Katherine.J.Hahn@medstar.net OI Malech, Harry/0000-0001-5874-5775 FU Intramural NIH HHS NR 7 TC 5 Z9 5 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 2015 VL 110 IS 6 BP 938 EP 939 DI 10.1038/ajg.2015.135 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CL6MS UT WOS:000357081800029 PM 26052777 ER PT J AU Pearce, N Blair, A Vineis, P Ahrens, W Andersen, A Anto, JM Armstrong, BK Baccarelli, AA Beland, FA Berrington, A Bertazzi, PA Birnbaum, LS Brownson, RC Bucher, JR Cantor, KP Cardis, E Cherrie, JW Christiani, DC Cocco, P Coggon, D Comba, P Demers, PA Dement, JM Douwes, J Eisen, EA Engel, LS Fenske, RA Fleming, LE Fletcher, T Fontham, E Forastiere, F Frentzel-Beyme, R Fritschi, L Gerin, M Goldberg, M Grandjean, P Grimsrud, TK Gustavsson, P Haines, A Hartge, P Hansen, J Hauptmann, M Heederik, D Hemminki, K Hemon, D Hertz-Picciotto, I Hoppin, JA Huff, J Jarvholm, B Kang, D Karagas, MR Kjaerheim, K Kjuus, H Kogevinas, M Kriebel, D Kristensen, P Kromhout, H Laden, F Lebailly, P LeMasters, G Lubin, JH Lynch, CF Lynge, E Mannetje, A McMichael, AJ McLaughlin, JR Marrett, L Martuzzi, M Merchant, JA Merler, E Merletti, F Miller, A Mirer, FE Monson, R Nordby, KC Olshan, AF Parent, ME Perera, FP Perry, MJ Pesatori, AC Pirastu, R Porta, M Pukkala, E Rice, C Richardson, DB Ritter, L Ritz, B Ronckers, CM Rushton, L Rusiecki, JA Rusyn, I Samet, JM Sandler, DP de Sanjose, S Schernhammer, E Costantini, AS Seixas, N Shy, C Siemiatycki, J Silverman, DT Simonato, L Smith, AH Smith, MT Spinelli, JJ Spitz, MR Stallones, L Stayner, LT Steenland, K Stenzel, M Stewart, BW Stewart, PA Symanski, E Terracini, B Tolbert, PE Vainio, H Vena, J Vermeulen, R Victora, CG Ward, EM Weinberg, CR Weisenburger, D Wesseling, C Weiderpass, E Zahm, SH AF Pearce, Neil Blair, Aaron Vineis, Paolo Ahrens, Wolfgang Andersen, Aage Anto, Josep M. Armstrong, Bruce K. Baccarelli, Andrea A. Beland, Frederick A. Berrington, Amy Bertazzi, Pier Alberto Birnbaum, Linda S. Brownson, Ross C. Bucher, John R. Cantor, Kenneth P. Cardis, Elisabeth Cherrie, John W. Christiani, David C. Cocco, Pierluigi Coggon, David Comba, Pietro Demers, Paul A. Dement, John M. Douwes, Jeroen Eisen, Ellen A. Engel, Lawrence S. Fenske, Richard A. Fleming, Lora E. Fletcher, Tony Fontham, Elizabeth Forastiere, Francesco Frentzel-Beyme, Rainer Fritschi, Lin Gerin, Michel Goldberg, Marcel Grandjean, Philippe Grimsrud, Tom K. Gustavsson, Per Haines, Andy Hartge, Patricia Hansen, Johnni Hauptmann, Michael Heederik, Dick Hemminki, Kari Hemon, Denis Hertz-Picciotto, Irva Hoppin, Jane A. Huff, James Jarvholm, Bengt Kang, Daehee Karagas, Margaret R. Kjaerheim, Kristina Kjuus, Helge Kogevinas, Manolis Kriebel, David Kristensen, Petter Kromhout, Hans Laden, Francine Lebailly, Pierre LeMasters, Grace Lubin, Jay H. Lynch, Charles F. Lynge, Elsebeth Mannetje, Andrea 't McMichael, Anthony J. McLaughlin, John R. Marrett, Loraine Martuzzi, Marco Merchant, James A. Merler, Enzo Merletti, Franco Miller, Anthony Mirer, Franklin E. Monson, Richard Nordby, Karl-Cristian Olshan, Andrew F. Parent, Marie-Elise Perera, Frederica P. Perry, Melissa J. Pesatori, Angela Cecilia Pirastu, Roberta Porta, Miquel Pukkala, Eero Rice, Carol Richardson, David B. Ritter, Leonard Ritz, Beate Ronckers, Cecile M. Rushton, Lesley Rusiecki, Jennifer A. Rusyn, Ivan Samet, Jonathan M. Sandler, Dale P. de Sanjose, Silvia Schernhammer, Eva Costantini, Adele Seniori Seixas, Noah Shy, Carl Siemiatycki, Jack Silverman, Debra T. Simonato, Lorenzo Smith, Allan H. Smith, Martyn T. Spinelli, John J. Spitz, Margaret R. Stallones, Lorann Stayner, Leslie T. Steenland, Kyle Stenzel, Mark Stewart, Bernard W. Stewart, Patricia A. Symanski, Elaine Terracini, Benedetto Tolbert, Paige E. Vainio, Harri Vena, John Vermeulen, Roel Victora, Cesar G. Ward, Elizabeth M. Weinberg, Clarice R. Weisenburger, Dennis Wesseling, Catharina Weiderpass, Elisabete Zahm, Shelia Hoar TI IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID PRINCIPLES UNDERLYING SCIENCE; PUBLIC-HEALTH; EPIDEMIOLOGIC ENTERPRISE; CANCER-EPIDEMIOLOGY; PLEA; POLICY; FALSE; ADHERENCE; PROGRAM; RECIPE AB BACKGROUND: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. OBJECTIVES: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. DISCUSSION: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health. C1 [Pearce, Neil] London Sch Hyg & Trop Med, Dept Med Stat, London WC1E 7HT, England. [Blair, Aaron; Berrington, Amy; Hartge, Patricia; Lubin, Jay H.; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England. [Ahrens, Wolfgang] Leibniz Inst Prevent Res & Epidemiol BIPS, Bremen, Germany. [Andersen, Aage; Grimsrud, Tom K.; Kjaerheim, Kristina] Canc Registry Norway, Dept Res, Oslo, Norway. [Anto, Josep M.] Univ Pompeu Fabra, Ctr Res Environm Epidemiol CREAL, IMIM Hosp Mar Med Res Inst, Barcelona, Spain. [Anto, Josep M.] CIBERESP, Barcelona, Spain. [Armstrong, Bruce K.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Armstrong, Bruce K.] Sax Inst, Sydney, NSW, Australia. [Baccarelli, Andrea A.; Christiani, David C.; Laden, Francine; Monson, Richard; Schernhammer, Eva] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Baccarelli, Andrea A.; Christiani, David C.; Laden, Francine; Monson, Richard; Schernhammer, Eva] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Bertazzi, Pier Alberto; Pesatori, Angela Cecilia] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. [Bertazzi, Pier Alberto; Pesatori, Angela Cecilia] IRCCS Fdn Ca Granda, Osped Maggiore Policlin, Milan, Italy. [Birnbaum, Linda S.] NCI, NIH, DHHS, Res Triangle Pk, NC USA. [Brownson, Ross C.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA. [Brownson, Ross C.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. [Bucher, John R.] NIEHS, Div Natl Toxicol Program, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Cantor, Kenneth P.] KP Cantor Environm LLC, Silver Spring, MD USA. [Cardis, Elisabeth] CREAL, IMIM, Barcelona, Spain. [Cardis, Elisabeth] CIBERESP, Barcelona, Spain. [Cherrie, John W.] Inst Occupat Med, Edinburgh, Midlothian, Scotland. [Cocco, Pierluigi] Univ Cagliari Monserrato, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy. [Coggon, David] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Comba, Pietro; Pirastu, Roberta] Charles Darwin Sapienza Rome Univ, Dept Biol & Biotechnol, Rome, Italy. [Demers, Paul A.] Canc Care Ontario, Occupat Canc Res Ctr, Toronto, ON, Canada. [Dement, John M.] Duke Univ, Med Ctr, Div Occupat & Environm Med, Durham, NC USA. [Douwes, Jeroen; Mannetje, Andrea 't] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Eisen, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Dept Environm Hlth Sci, Berkeley, CA 94720 USA. [Eisen, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA. [Engel, Lawrence S.; Olshan, Andrew F.; Richardson, David B.; Shy, Carl] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Fenske, Richard A.; Seixas, Noah] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Fleming, Lora E.] Univ Exeter, Sch Med, European Ctr Environm & Human Hlth, Truro, Cornwall, England. London Sch Hyg & Trop Med, Dept Social & Environm Hlth Res, London WC1, England. [Fontham, Elizabeth] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA. [Forastiere, Francesco] Lazio Reg Hlth Serv, Dept Epidemiol, Rome, Italy. [Frentzel-Beyme, Rainer] Univ Bremen, Ctr Environm Res & Sustainable Technol UFT, D-28359 Bremen, Germany. [Fritschi, Lin] Curtin Univ, Sch Publ Hlth, Perth, WA 6845, Australia. [Gerin, Michel] Univ Montreal, Ecole Sante Publ, Dept Environm & Occupat Hlth, Montreal, PQ, Canada. [Goldberg, Marcel] INSERM, UMS 011, Populat Based Epidemiol Cohorts Unit, Villejuif, France. [Grandjean, Philippe] Univ Southern Denmark, Dept Environm Med, Odense, Denmark. Karolinska Inst, Inst Environm Med IMM, Stockholm, Sweden. [Hansen, Johnni] Danish Canc Soc, Res Ctr, Copenhagen, Denmark. [Hauptmann, Michael] Netherlands Canc Inst, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Heederik, Dick; Kromhout, Hans; Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands. [Hemminki, Kari] German Canc Res Ctr, Heidelberg, Germany. [Hemon, Denis] Paris Descartes Univ, Epidemiol & Biostat Sorbonne Paris Cite Ctr CRESS, Epidemiol Childhood & Adolescent Canc Res Grp EPI, INSERM,UMR 1153, F-75015 Paris, France. [Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Hoppin, Jane A.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. [Huff, James] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Jarvholm, Bengt] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Kang, Daehee] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Karagas, Margaret R.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Kjuus, Helge; Kristensen, Petter; Nordby, Karl-Cristian] Natl Inst Occupat Hlth, Oslo, Norway. [Kogevinas, Manolis] CREAL, IMIM, Barcelona, Spain. [Kogevinas, Manolis] CIBERESP, Barcelona, Spain. [Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece. [Kriebel, David] Univ Massachusetts, Dept Work Environm, Lowell, MA USA. [Lebailly, Pierre] Univ Caen, Ctr Francois Baclesse, F-14032 Caen, France. [LeMasters, Grace] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Lynch, Charles F.; Merchant, James A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Lynge, Elsebeth] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark. [McMichael, Anthony J.] Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia. [McLaughlin, John R.] Publ Hlth Ontario, Toronto, ON, Canada. [Marrett, Loraine] Univ Toronto, Prevent & Canc Control, Canc Care Ontario, Toronto, ON, Canada. [Marrett, Loraine] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Martuzzi, Marco] WHO, Reg Off Europe, European Ctr Environm & Hlth, Bonn, Germany. [Merler, Enzo] Local Hlth Author, Natl Hlth Serv, Reg Mesothelioma Register, Padua, Italy. [Merletti, Franco] Univ Turin, Dept Med Sci, Unit Canc Epidemiol, Turin, Italy. [Miller, Anthony] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Mirer, Franklin E.] CUNY, Sch Publ Hlth, New York, NY 10021 USA. [Parent, Marie-Elise] Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ, Canada. [Perera, Frederica P.] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA. [Perera, Frederica P.] Columbia Univ, Mailman Sch Publ Hlth, Columbia Ctr Childrens Environm Hlth, New York, NY USA. [Perry, Melissa J.] George Washington Univ, Sch Publ Hlth, Milken Inst, Dept Environm & Occupat Hlth, Washington, DC USA. [Porta, Miquel] Univ Autonoma Barcelona, IMIM, CIBERESP, E-08193 Barcelona, Spain. [Porta, Miquel] Univ Autonoma Barcelona, Sch Med, E-08193 Barcelona, Spain. [Pukkala, Eero] Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FIN-00170 Helsinki, Finland. [Pukkala, Eero] Univ Tampere, Sch Hlth Sci, Tampere, Finland. [Rice, Carol] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH USA. [Ritter, Leonard] Univ Guelph, Ontario Agr Coll, Sch Environm Sci, Guelph, ON N1G 2W1, Canada. [Ritz, Beate] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Ronckers, Cecile M.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hospi, Dept Pediat Oncol, NL-1105 AZ Amsterdam, Netherlands. [Rushton, Lesley] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England. [Rusiecki, Jennifer A.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Rusyn, Ivan] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA. [Samet, Jonathan M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [de Sanjose, Silvia; Siemiatycki, Jack] CIBERESP Catalan Inst Oncol, Bellvitge Biomed Res Inst IDIBELL, Unit Infect & Canc, Canc Epidemiol Res Programme, Barcelona, Spain. [Costantini, Adele Seniori] Canc Prevent & Res Inst ISPO, Florence, Italy. [Siemiatycki, Jack] Univ Montreal, Ecole Sante Publ, Dept Social & Prevent Med, Montreal, PQ, Canada. [Simonato, Lorenzo] Univ Padua, Dept Mol Med, Lab Publ Hlth & Populat Studies, Padua, Italy. [Smith, Allan H.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Environm Hlth Sci, Berkeley, CA 94720 USA. [Vainio, Harri] Univ British Columbia, Canc Control Res, BC Canc Agcy, Vancouver, BC, Canada. [Vainio, Harri] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada. [Spitz, Margaret R.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Stallones, Lorann] Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA. [Stayner, Leslie T.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA. [Steenland, Kyle; Tolbert, Paige E.] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA. [Stenzel, Mark] Exposure Assessment Applicat LLC, Arlington, VA USA. [Stewart, Bernard W.] South East Sydney Publ Hlth Unit, Canc Control Program, Randwick, NSW, Australia. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA. [Symanski, Elaine] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Terracini, Benedetto] Univ Turin, Turin, Italy. [Terracini, Benedetto] CPO Piemonte, Ctr Riferimento Epidemiol & Prevenz Oncol, Turin, Italy. [Vainio, Harri] Finnish Inst Occupat Hlth, Helsinki, Finland. [Vena, John] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Victora, Cesar G.] Univ Fed Pelotas, Rio Grande Do Sul, Brazil. [Ward, Elizabeth M.] Amer Canc Soc Inc, Atlanta, GA USA. [Weinberg, Clarice R.] NIEHS, Biostat & Computat Biol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Weisenburger, Dennis] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Wesseling, Catharina] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Weiderpass, Elisabete] UiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, Tromso, Norway. [Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway. [Weiderpass, Elisabete] Genet Epidemiol Grp, Folkhalsan Res Ctr, Helsinki, Finland. [Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Zahm, Shelia Hoar] Shelia Zahm Consulting, Hermon, ME USA. RP Pearce, N (reprint author), London Sch Hyg & Trop Med, Dept Med Stat, Keppel St, London WC1E 7HT, England. EM neil.pearce@lshtm.ac.uk RI Fritschi, Lin /K-2096-2012; Porta, Miquel/B-5787-2008; Cardis, Elisabeth/C-3904-2017; Kogevinas, Manolis/C-3918-2017; Vermeulen, Roel/F-8037-2011; Armstrong, Bruce/K-9464-2015; LEBAILLY, Pierre/L-7351-2015; de Sanjose Llongueras, Silvia/H-6339-2014; Forastiere, Francesco/J-9067-2016; Weiderpass, Elisabete/M-4029-2016; Rusyn, Ivan/S-2426-2016; Victora, Cesar/D-4476-2013; Anto, J/H-2676-2014; bertazzi, pietro alberto/D-5039-2017; OI Fritschi, Lin /0000-0002-7692-3560; Porta, Miquel/0000-0003-1684-7428; Vermeulen, Roel/0000-0003-4082-8163; Armstrong, Bruce/0000-0001-8940-7525; Forastiere, Francesco/0000-0002-9162-5684; Weiderpass, Elisabete/0000-0003-2237-0128; Anto, J/0000-0002-4736-8529; bertazzi, pietro alberto/0000-0003-3475-2449; Pirastu, Roberta/0000-0003-1192-2732; Baccarelli, Andrea/0000-0002-3436-0640; Douwes, Jeroen/0000-0003-3599-4036; Lynge, Elsebeth/0000-0003-4785-5236; Kjaerheim, Kristina/0000-0003-0691-3735; pesatori, angela/0000-0002-0261-3252; Victora, Cesar/0000-0002-2465-2180; Sandler, Dale/0000-0002-6776-0018; Engel, Lawrence/0000-0001-9268-4830; Ahrens, Wolfgang/0000-0003-3777-570X FU NIH (NCI); NIH (NIEHS) FX This work was conducted with no direct funding, but was supported in part by the Intramural Research Program of the NIH (NCI and NIEHS). NR 43 TC 8 Z9 9 U1 4 U2 36 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2015 VL 123 IS 6 BP 507 EP 514 DI 10.1289/ehp.1409149 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CL9KD UT WOS:000357296200010 PM 25712798 ER PT J AU Deziel, NC Friesen, MC Hoppin, JA Hines, CJ Thomas, K Freeman, LEB AF Deziel, Nicole C. Friesen, Melissa C. Hoppin, Jane A. Hines, Cynthia J. Thomas, Kent Freeman, Laura E. Beane TI A Review of Nonoccupational Pathways for Pesticide Exposure in Women Living in Agricultural Areas SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review ID URINARY METABOLITE LEVELS; FARM FAMILY EXPOSURE; HERBICIDE EXPOSURE; CHILDRENS EXPOSURE; PREGNANT-WOMEN; ONTARIO FARMS; UNITED-STATES; COMMUNITY; PROXIMITY; HOMES AB BACKGROUND: Women living in agricultural areas may experience high pesticide exposures compared with women in urban or suburban areas because of their proximity to farm activities. OBJECTIVE: Our objective was to review the evidence in the published literature for the contribution of nonoccupational pathways of pesticide exposure in women living in North American agricultural areas. METHODS: We evaluated the following nonoccupational exposure pathways: para-occupational (i.e., take-home or bystander exposure), agricultural drift, residential pesticide use, and dietary ingestion. We also evaluated the role of hygiene factors (e.g., house cleaning, shoe removal). RESULTS: Among 35 publications identified (published 1995-2013), several reported significant or suggestive (p < 0.1) associations between para-occupational (n = 19) and agricultural drift (n = 10) pathways and pesticide dust or biomarker levels, and 3 observed that residential use was associated with pesticide concentrations in dust. The 4 studies related to ingestion reported low detection rates of most pesticides in water; additional studies are needed to draw conclusions about the importance of this pathway. Hygiene factors were not consistently linked to exposure among the 18 relevant publications identified. CONCLUSIONS: Evidence supported the importance of para-occupational, drift, and residential use pathways. Disentangling exposure pathways was difficult because agricultural populations are concurrently exposed to pesticides via multiple pathways. Most evidence was based on measurements of pesticides in residential dust, which are applicable to any household member and are not specific to women. An improved understanding of nonoccupational pesticide exposure pathways in women living in agricultural areas is critical for studying health effects in women and for designing effective exposure-reduction strategies. C1 [Deziel, Nicole C.; Friesen, Melissa C.; Freeman, Laura E. Beane] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Deziel, Nicole C.] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06510 USA. [Hoppin, Jane A.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA. [Hines, Cynthia J.] Ctr Dis Control & Prevent, Natl Inst Occupat Safety & Hlth, Div Surveillance Hazard Evaluat & Field Studie, Cincinnati, OH USA. [Thomas, Kent] US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA. RP Deziel, NC (reprint author), Yale Univ, Sch Publ Hlth, 60 Coll St, New Haven, CT 06510 USA. EM nicole.deziel@yale.edu RI Friesen, Melissa/A-5362-2009; Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics [Z01CP010119] FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (Z01CP010119). NR 52 TC 9 Z9 10 U1 5 U2 24 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2015 VL 123 IS 6 BP 515 EP 524 DI 10.1289/ehp.1408273 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CL9KD UT WOS:000357296200011 PM 25636067 ER PT J AU Elagha, AA Ruiz, G Fuisz, AR AF Elagha, A. A. Ruiz, G. Fuisz, A. R. TI Remarkable improvement in ventricular function after reversion to normal sinus rhythm Cardiac MRI study in a patient with single ventricle s/p Fontan procedure SO HERZ LA English DT Editorial Material C1 [Elagha, A. A.] Cairo Univ Hosp, Dept Cardiol, Cairo, Egypt. [Elagha, A. A.; Ruiz, G.; Fuisz, A. R.] Washington Hosp Ctr, Dept Med, Cardiol Sect, Washington, DC 20010 USA. [Elagha, A. A.] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA. RP Elagha, AA (reprint author), Cairo Univ Hosp, Dept Cardiol, Cairo, Egypt. EM elaghaa@mail.nih.gov OI Elagha, Abdalla/0000-0003-3136-2293 NR 4 TC 1 Z9 1 U1 0 U2 1 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0340-9937 EI 1615-6692 J9 HERZ JI Herz PD JUN PY 2015 VL 40 IS 4 BP 629 EP 631 DI 10.1007/s00059-013-3953-5 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK5LM UT WOS:000356266000010 PM 24135877 ER PT J AU Kristinsson, SY Gao, Y Bjorkholm, M Lund, SH Sjoberg, J Caporaso, N Goldin, LR Landgren, O AF Kristinsson, Sigurdur Y. Gao, Ying Bjorkholm, Magnus Lund, Sigrun Helga Sjoberg, Jan Caporaso, Neil Goldin, Lynn R. Landgren, Ola TI Hodgkin lymphoma risk following infectious and chronic inflammatory diseases: a large population-based case-control study from Sweden SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Hodgkin lymphoma; Infection; Inflammation; Chronic immune stimulation; Pathogenesis; Immune deficiency ID PROGNOSIS; DISORDERS; SIBLINGS; BIOLOGY; FAMILY; YOUNG AB Patients with Hodgkin lymphoma (HL) have a well-characterized immune deficiency of T cell function, originally identified by increased susceptibility to certain infections. Epidemiological evidence has long pointed to infectious etiologies in younger HL patients. With the aim of expanding our knowledge on the potential role of preexisting immune deficiency in HL and an infectious/inflammatory etiology, we conducted a comprehensive population-based case-control study in HL patients diagnosed in Sweden in the period 1965-2004, and their matched controls. In a large population-based study including 7,414 HL patients and 29,240 matched controls, we evaluated the subsequent risk of HL in relation to a broad range of infectious and inflammatory conditions, using unconditional logistic regression. A previous history of any reported infection was associated with an 11 % increased risk of HL (P < 0.05). More specifically, we found sinusitis (odds ratio = 1.81; 95 % confidence interval = 1.06-3.07), tuberculosis (1.76; 1.01-3.07), encephalitis (7.88; 1.97-31.5), and herpes zoster (2.20; 1.11-4.35) to be associated with excess HL risk. A personal prior history of chronic inflammatory condition was not associated with an increased risk of HL (0.94; 0.71-1.14). Our results suggest that underlying immune deficiency is a primary phenomenon in HL. Alternatively, certain infectious agents may be potential HL triggers. C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Sjoberg, Jan; Landgren, Ola] Karolinska Univ, Hosp Solna & Inst, Div Hematol, Dept Med, S-17176 Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Lund, Sigrun Helga] Univ Iceland, Fac Med, Reykjavik, Iceland. [Gao, Ying; Caporaso, Neil; Goldin, Lynn R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, New York, NY 10021 USA. RP Kristinsson, SY (reprint author), Karolinska Univ, Hosp Solna & Inst, Div Hematol, Dept Med, S-17176 Stockholm, Sweden. EM sigurdur.kristinsson@ki.se RI Kristinsson, Sigurdur /M-2910-2015; Lund, Sigrun Helga/K-9144-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476; Lund, Sigrun Helga/0000-0002-3806-2296 FU NIH; NCI; Swedish Cancer Society; Stockholm County Council; Karolinska Institutet Foundations FX This research was supported by grants from the Intramural Research Program of the NIH, NCI, Swedish Cancer Society, Stockholm County Council, and the Karolinska Institutet Foundations. The authors thank Ms. Shiva Ayobi, The National Board of Health and Welfare, Stockholm, Sweden; Ms. Susanne Dahllof, Statistics Sweden, Orebro, Sweden; and Ms. Emily Steplowski, Information Management Services, Silver Spring, MD, for important efforts in the development of this database. NR 27 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0925-5710 EI 1865-3774 J9 INT J HEMATOL JI Int. J. Hematol. PD JUN PY 2015 VL 101 IS 6 BP 563 EP 568 DI 10.1007/s12185-015-1772-6 PG 6 WC Hematology SC Hematology GA CM2NY UT WOS:000357519200006 PM 25758095 ER PT J AU Yang, J Andre, P Ye, L Yang, YZ AF Yang, Jing Andre, Philipp Ye, Ling Yang, Yhig-Zi TI The Hedgehog signalling pathway in bone formation SO INTERNATIONAL JOURNAL OF ORAL SCIENCE LA English DT Review DE bone development; bone disease; endochondral ossification; hedgehog; homeostasis; joint formation; patterning ID CELL CARCINOMA SYNDROME; MESSENGER-RNA EXPRESSION; MESENCHYMAL STEM-CELLS; SONIC-HEDGEHOG; INDIAN HEDGEHOG; CUBITUS-INTERRUPTUS; PRIMARY CILIUM; GROWTH-PLATE; OSTEOBLAST DIFFERENTIATION; MORPHOGENETIC PROTEIN AB The Hedgehog (Hh) signalling pathway plays many important roles in development, homeostasis and tumorigenesis. The critical function of Hh signalling in bone formation has been identified in the past two decades. Here, we review the evolutionarily conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development, homeostasis and diseases. In the early stages of embryonic limb development, Sonic Hedgehog (Shh) acts as a major morphogen in patterning the limb buds. Indian Hedgehog (Ihh) has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium. Hh signalling is also involved intramembrane ossification. Interactions between Hh and Wnt signalling regulate cartilage development, endochondral bone formation and synovial joint formation. Hh also plays an important role in bone homeostasis, and reducing Hh signalling protects against age-related bone loss. Disruption of Hh signalling regulation leads to multiple bone diseases, such as progressive osseous heteroplasia. Therefore, understanding the signalling mechanisms and functions of Hh signalling in bone development, homeostasis and diseases will provide important insights into bone disease prevention, diagnoses and therapeutics. C1 [Yang, Jing; Ye, Ling] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China. [Yang, Jing; Andre, Philipp; Yang, Yhig-Zi] NHGRI, Genet Dis Res, NIH, Bethesda, MD 20892 USA. [Yang, Yhig-Zi] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Ye, L (reprint author), Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, 14,Sect 3,Renmin South Rd, Chengdu 610041, Peoples R China. EM yeling@scu.edu.cn; yingzi@mail.nih.gov FU intramural research programme, NHGRI, National Institutes of Health (NIH); National Science Foundation for Excellent Young Scholars of China [813220170]; Innovation Team of Sichuan Province [2015TD0011]; China Scholarship Council FX This work is supported by an intramural research programme, NHGRI, National Institutes of Health (NIH); the National Science Foundation for Excellent Young Scholars of China (grant no. 813220170); the Innovation Team of Sichuan Province (2015TD0011); and the China Scholarship Council. NR 134 TC 10 Z9 10 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1674-2818 EI 2049-3169 J9 INT J ORAL SCI JI Int. J. Oral Sci. PD JUN PY 2015 VL 7 IS 2 BP 73 EP 79 DI 10.1038/ijos.2015.14 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CM5CG UT WOS:000357703800002 PM 26023726 ER PT J AU Tandon, A Chen, CJ Penman, A Hancock, H James, M Husain, D Andreoli, C Li, XH Kuo, JZ Idowu, O Riche, D Papavasilieou, E Brauner, S Smith, SO Hoadley, S Richardson, C Kieser, T Vazquez, V Chi, C Fernandez, M Harden, M Cotch, MF Siscovick, D Taylor, HA Wilson, JG Reich, D Wong, TY Klein, R Klein, BEK Rotter, JI Patterson, N Sobrin, L AF Tandon, Arti Chen, Ching J. Penman, Alan Hancock, Heather James, Maurice Husain, Deeba Andreoli, Christopher Li, Xiaohui Kuo, Jane Z. Idowu, Omolola Riche, Daniel Papavasilieou, Evangelia Brauner, Stacey Smith, Sataria O. Hoadley, Suzanne Richardson, Cole Kieser, Troy Vazquez, Vanessa Chi, Cheryl Fernandez, Marlene Harden, Maegan Cotch, Mary Frances Siscovick, David Taylor, Herman A. Wilson, James G. Reich, David Wong, Tien Y. Klein, Ronald Klein, Barbara E. K. Rotter, Jerome I. Patterson, Nick Sobrin, Lucia TI African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE genetics; diabetic retinopathy; proliferative diabetic retinopathy; African Americans; admixture; ancestry ID ASSOCIATION RESOURCE CARE; RISK-FACTORS; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; UNITED-STATES; METAANALYSIS; DISEASE; PROGRESSION; POPULATION; DESIGN AB PURPOSE. To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). METHODS. Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A(1C), systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. RESULTS. In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16-1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59-2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. CONCLUSIONS. In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present. C1 [Tandon, Arti; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Tandon, Arti; Reich, David; Patterson, Nick] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Chen, Ching J.; Hancock, Heather; Idowu, Omolola; Smith, Sataria O.; Hoadley, Suzanne; Richardson, Cole] Univ Mississippi, Med Ctr, Dept Ophthalmol, Jackson, MS 39216 USA. [Penman, Alan; Riche, Daniel; Taylor, Herman A.; Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Penman, Alan] Univ Mississippi, Med Ctr, Dept Biostat, Jackson, MS 39216 USA. [James, Maurice] St Dominics Hosp, Ophthalmol, Jackson, MS USA. [Husain, Deeba; Papavasilieou, Evangelia; Brauner, Stacey; Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Andreoli, Christopher; Kieser, Troy] Harvard Vanguard Med Associates, Visual Serv Dept, Boston, MA USA. [Li, Xiaohui; Kuo, Jane Z.; Rotter, Jerome I.] LABiomed, Inst Translat Genom & Populat Sci, Torrance, CA USA. [Li, Xiaohui; Kuo, Jane Z.; Rotter, Jerome I.] Harbor UCLA, Dept Pediat, Torrance, CA USA. [Kuo, Jane Z.] Pathway Genom Corp, San Diego, CA USA. [Vazquez, Vanessa; Chi, Cheryl] Boston Med Ctr, Dept Ophthalmol, Boston, MA USA. [Fernandez, Marlene] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Harden, Maegan] Broad Inst, Genom Platform, Cambridge, MA USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Wong, Tien Y.] Natl Univ Singapore, Off Clin Sci, Duke NUS Grad Med Sch, Singapore 117548, Singapore. [Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. RP Sobrin, L (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St,12th Floor, Boston, MA 02114 USA. EM lucia_sobrin@meei.harvard.edu OI Cotch, Mary Frances/0000-0002-2046-4350 FU American Diabetes Association Clinical Translational Research Award (Alexandria, VA, USA) [1-11-CT-51]; National Eye Institute (Bethesda, MD, USA) [K12-EY16335]; Research to Prevent Blindness Career Development Award (New York City, NY, USA); Harvard Catalyst \ The Harvard Clinical and Translations Science Center Faculty Fellowship (Boston, MA, USA); Massachusetts Lions Eye Research Fund (Abington, MA, USA); Eleanor and Miles Shore Fellowship (Boston, MA, USA); Sara Elizabeth O'Brien Trust (Boston, MA, USA); National Heart, Lung Blood Institute (NHLBI) (Bethesda, MD, USA) [N01-HC-65226]; Atherosclerosis Risk in Communities (ARIC) Study; Jackson Heart Study (JHS); Multi-Ethnic Study of Atherosclerosis (MESA) FX Supported by grants from the American Diabetes Association Clinical Translational Research Award 1-11-CT-51 (Alexandria, VA, USA), National Eye Institute Grant K12-EY16335 (Bethesda, MD, USA), Research to Prevent Blindness Career Development Award (New York City, NY, USA), Harvard Catalyst vertical bar The Harvard Clinical and Translations Science Center Faculty Fellowship (Boston, MA, USA), Massachusetts Lions Eye Research Fund (Abington, MA, USA), Eleanor and Miles Shore Fellowship (Boston, MA, USA), Sara Elizabeth O'Brien Trust (Boston, MA, USA). The National Heart, Lung Blood Institute (NHLBI) Grant N01-HC-65226 (Bethesda, MD, USA) has supported genotyping and has created a genotype-phenotype database with data and samples from nine cohorts as part of Candidate Gene Association Resource (CARe). Please see the Supplementary Material for detailed information about the grants supporting three cohorts that were part of this study: Atherosclerosis Risk in Communities (ARIC) Study, Jackson Heart Study (JHS) and Multi-Ethnic Study of Atherosclerosis (MESA). NR 50 TC 0 Z9 0 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2015 VL 56 IS 6 BP 3999 EP 4005 DI 10.1167/iovs.15-16674 PG 7 WC Ophthalmology SC Ophthalmology GA CM5PJ UT WOS:000357740200065 PM 26098467 ER PT J AU Normand, J AF Normand, Jacques TI Preface SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Editorial Material C1 [Normand, Jacques] NIDA, NIH, Rockville, MD USA. RP Normand, J (reprint author), NIDA, AIDS Res Program, 6001 Execut Blvd,Room 5274,MSC 9581, Bethesda, MD 20892 USA. EM jnormand@nida.nih.gov FU PHS HHS [HHSN271201100021C] NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN 1 PY 2015 VL 69 SU 2 BP S93 EP S93 DI 10.1097/QAI.0000000000000661 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CL9TK UT WOS:000357320800001 PM 25978487 ER PT J AU Negussie, AH Dreher, MR Johnson, CG Tang, YQ Lewis, AL Storm, G Sharma, KV Wood, BJ AF Negussie, Ayele H. Dreher, Matthew R. Johnson, Carmen Gacchina Tang, Yiqing Lewis, Andrew L. Storm, Gert Sharma, Karun V. Wood, Bradford J. TI Synthesis and characterization of image-able polyvinyl alcohol microspheres for image-guided chemoembolization SO JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE LA English DT Article ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; TRISACRYL GELATIN MICROSPHERES; DRUG-ELUTING BEADS; CEREBRAL ARTERIOVENOUS-MALFORMATIONS; RADIOPAQUE HYDROGEL MICROSPHERES; TRANS-ARTERIAL CHEMOEMBOLIZATION; METASTATIC COLORECTAL-CARCINOMA; RANDOMIZED CONTROLLED TRIAL; P-STYRENE SULFONATE; TRANSARTERIAL CHEMOEMBOLIZATION AB Therapeutic embolization of blood vessels is a minimally invasive, catheter-based procedure performed with solid or liquid emboli to treat bleeding, vascular malformations, and vascular tumors. Hepatocellular carcinoma (HCC) affects about half a million people per year. When unresectable, HCC is treated with embolization and local drug therapy by transarterial chemoembolization (TACE). For TACE, drug eluting beads (DC Bead (R)) may be used to occlude or reduce arterial blood supply and deliver chemotherapeutics locally to the tumor. Although this treatment has been shown to be safe and to improve patient survival, the procedure lacks imaging feedback regarding the location of embolic agent and drug coverage. To address this shortcoming, herein we report the synthesis and characterization of image-able drug eluting beads (iBeads) from the commercial DC Bead (R) product. Two different radiopaque beads were synthesized. In one approach, embolic beads were conjugated with 2,3,5-triiodobenzyl alcohol in the presence of 1,10-carbonyldiimidazol to give iBead I. iBead II was synthesized with a similar approach but instead using a trimethylenediamine spacer and 2,3,5-triiodobenzoic acid. Doxorubicin was loaded into the iBeads II using a previously reported method. Size and shape of iBeads were evaluated using an upright microscope and their conspicuity assessed using a clinical CT and micro-CT. Bland and Dox-loaded iBeads II visualized with both clinical CT and microCT. Under microCT, individual bland and Dox loaded beads had a mean attenuation of 7904 +/- 804 and 11,873.96 +/- 706.12 HU, respectively. These iBeads have the potential to enhance image-guided TACE procedures by providing localization of embolic-particle and drug. C1 [Negussie, Ayele H.; Dreher, Matthew R.; Johnson, Carmen Gacchina; Sharma, Karun V.; Wood, Bradford J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20814 USA. [Tang, Yiqing; Lewis, Andrew L.] Bioccompatibles UK Ltd, Farnham GU9 8QL, Surrey, England. [Negussie, Ayele H.; Storm, Gert] Univ Twente, MIRA Inst, Dept Targeted Therapeut, NL-7500 AE Enschede, Netherlands. [Storm, Gert] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, Utrecht, Netherlands. RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20814 USA. EM negussiea@cc.nih.gov; matthew.dreher@gmail.com; carmengacchina@gmail.com; Yiqing.Tang@btgplc.com; Andrew.Lewis@btgplc.com; G.Storm@uu.nl; KVSharma@childrensnational.org; bwood@cc.nih.gov RI Storm, Gert/O-8696-2016; OI Negussie, Ayele/0000-0003-3340-3351; Lewis, Andrew/0000-0001-5779-5631 FU Center for Interventional Oncology in the Intramural Research Program of the National Institutes of Health (NIH); Imaging Sciences Training Program of the National Institutes of Health FX This research was supported by the Center for Interventional Oncology in the Intramural Research Program of the National Institutes of Health (NIH). NIH and Biocompatibles UK Ltd, a BTG International group company have a Cooperative Research and Development Agreement. C.G.J. was supported by the Imaging Sciences Training Program of the National Institutes of Health. We would like to thank Belhu Metaferia, for his advice and useful discussions. NR 88 TC 4 Z9 4 U1 5 U2 20 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 JUN PY 2015 VL 26 IS 6 AR 198 DI 10.1007/s10856-015-5530-3 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CM2SL UT WOS:000357532300009 PM 26105830 ER PT J AU Gebreab, SY Davis, SK Symanzik, J Mensah, GA Gibbons, GH Diez-Roux, AV AF Gebreab, Samson Y. Davis, Sharon K. Symanzik, Juergen Mensah, George A. Gibbons, Gary H. Diez-Roux, Ana V. TI Geographic Variations in Cardiovascular Health in the United States: Contributions of State- and Individual-Level Factors SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE cardiovascular health; geographic variation; individual- and state-level factors; linked micromap plots; multilevel analysis ID FACTOR SURVEILLANCE SYSTEM; NUTRITION EXAMINATION SURVEYS; AMERICAN-HEART-ASSOCIATION; LINKED MICROMAP PLOTS; MULTILEVEL ANALYSIS; PHYSICAL-ACTIVITY; NATIONAL-HEALTH; US ADULTS; INCOME INEQUALITY; DISEASE RISK AB Background-Improving cardiovascular health (CVH) of all Americans by 2020 is a strategic goal of the American Heart Association. Understanding the sources of variation and identifying contextual factors associated with poor CVH may suggest important avenues for prevention. Methods and Results-Cross-sectional data from the Behavioral Risk Factor Surveillance System for the year 2011 were linked to state-level coronary heart disease and stroke mortality data from the National Vital Statistics System and to state-level measures of median household income, income inequality, taxes on soda drinks and cigarettes, and food and physical activity environments from various administrative sources. Poor CVH was defined according to the American Heart Association definition using 7 selfreported CVH metrics (current smoking, physical inactivity, obesity, poor diet, hypertension, diabetes, and high cholesterol). Linked micromap plots and multilevel logistic models were used to examine state variation in poor CVH and to investigate the contributions of individual-and state-level factors to this variation. We found significant state-level variation in the prevalence of poor CVH (median odds ratio 1.32, P<0.001). Higher rates of poor CVH and cardiovascular disease mortality were clustered in the southern states. Minority and low socioeconomic groups were strongly associated with poor CVH and explained 44% of the state-level variation in poor CVH; state-level factors explained an additional 28%. State-level median household income (odds ratio 0.89; 95% CI 0.84-0.94), taxes on soda drinks (odds ratio 0.94; 95% CI 0.89-0.99), farmers markets (odds ratio 0.91; 95% CI 0.85-0.98), and convenience stores (odds ratio 1.09; 95% CI 1.01-1.17) were predictive of poor CVH even after accounting for individual-level factors. Conclusions-There is significant state-level variation in poor CVH that is partly explained by individual-and state-level factors. Additional longitudinal research is warranted to examine the influence of state-level policies and food and physical activity environments on poor CVH. C1 [Gebreab, Samson Y.; Davis, Sharon K.; Gibbons, Gary H.] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA. [Symanzik, Juergen] Utah State Univ, Dept Stat, Logan, UT 84322 USA. [Mensah, George A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Diez-Roux, Ana V.] Univ Michigan, Michigan Ctr Integrat Approaches Hlth Dispar CIAH, Ann Arbor, MI 48109 USA. [Diez-Roux, Ana V.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. RP Gebreab, SY (reprint author), NHGRI, NIH, Genom Metab Cardiovasc & Inflammatory Dis Branch, Cardiovasc Sect,Social Epidemiol Res Unit, Bethesda, MD 20892 USA. EM samson.gebreab@nih.gov FU Intermural Program of National Human Genomics Institute, NIH; Michigan Center for Integrative Approaches to Health Disparities - National Institute on Minority Health and Health Disparities [2P60MD002249] FX This research is supported by Intermural Program of National Human Genomics Institute, NIH. Dr Ana V. Diez-Roux was supported by Michigan Center for Integrative Approaches to Health Disparities (2P60MD002249) funded by the National Institute on Minority Health and Health Disparities. NR 61 TC 13 Z9 13 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2015 VL 4 IS 6 AR e001673 DI 10.1161/JAHA.114.001673 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL5TV UT WOS:000357025100011 PM 26019131 ER PT J AU Gebreab, SY Roux, AVD Brenner, AB Hickson, DA Sims, M Subramanyam, M Griswold, ME Wyatt, SB James, SA AF Gebreab, Samson Y. Roux, Ana V. Diez Brenner, Allison B. Hickson, DeMarc A. Sims, Mario Subramanyam, Malavika Griswold, Michael E. Wyatt, Sharon B. James, Sherman A. TI The Impact of Lifecourse Socioeconomic Position on Cardiovascular Disease Events in African Americans: The Jackson Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE adult SEP; African Americans; cardiovascular disease events; childhood SEP; epidemiology; lifecourse; socioeconomic position ID CAUSE-SPECIFIC MORTALITY; CVD RISK-FACTORS; YOUNG-ADULTS; RACIAL-DISCRIMINATION; ATHEROSCLEROSIS RISK; UNITED-STATES; CHILDHOOD; HEALTH; WOMEN; CIRCUMSTANCES AB Background-Few studies have examined the impact of lifecourse socioeconomic position (SEP) on cardiovascular disease (CVD) risk among African Americans. Methods and Results-We used data from the Jackson Heart Study (JHS) to examine the associations of multiple measures of lifecourse SEP with CVD events in a large cohort of African Americans. During a median of 7.2-year follow-up, 362 new or recurrent CVD events occurred in a sample of 5301 participants aged 21 to 94. Childhood SEP was assessed by using mother's education, parental home ownership, and childhood amenities. Adult SEP was assessed by using education, income, wealth, and public assistance. Adult SEP was more consistently associated with CVD risk in women than in men: age-adjusted hazard ratios for low versus high income (95% CIs), 2.46 (1.19 to 5.09) in women and 1.50 (0.87 to 2.58) in men, P for interaction=0.1244, and hazard ratio for low versus high wealth, 2.14 (1.39 to 3.29) in women and 1.06 (0.62 to 1.81) in men, P for interaction=0.0224. After simultaneous adjustment for all adult SEP measures, wealth remained a significant predictor of CVD events in women (HR=1.73 [1.04, 2.85] for low versus high). Education and public assistance were less consistently associated with CVD. Adult SEP was a stronger predictor of CVD events in younger than in older participants (HR for high versus low summary adult SEP score 3.28 [1.43, 7.53] for participants <= 50 years, and 1.90 (1.36 to 2.66) for participants >50 years, P for interaction 0.0846). Childhood SEP was not associated with CVD risk in women or men. Conclusions-Adult SEP is an important predictor of CVD events in African American women and in younger African Americans. Childhood SEP was not associated with CVD events in this population. C1 [Gebreab, Samson Y.] NHGRI, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA. [Roux, Ana V. Diez] Drexel Univ, Michigan Ctr Integrat Approaches Hlth Dispar CIAH, Philadelphia, PA 19104 USA. [Roux, Ana V. Diez] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Brenner, Allison B.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Hickson, DeMarc A.; Sims, Mario; Griswold, Michael E.; Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Sch Med, Jackson, MS 39216 USA. [Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA. [Sims, Mario] Indian Inst Technol, Gandhinagar, India. [James, Sherman A.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. RP Gebreab, SY (reprint author), NHGRI, NIH, Metab Cardiovasc & Inflammatory Dis Genom Branch, Cardiovasc Sect,Social Epidemiol Res Unit, 10 Ctr Dr,MSC 1644, Bethesda, MD 20892 USA. EM samson.gebreab@nih.gov FU Michigan Center for Integrative Approaches to Health Disparities - National Institute on Minority Health and Health Disparities [2P60MD00 2249]; National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN 268201300050C]; National Institute on Minority Health and Health Disparities, Bethesda, MD; Intermural Program of National Human Genomics Institute, NIH, Bethesda, MD FX This research is supported by the Michigan Center for Integrative Approaches to Health Disparities (2P60MD00 2249) funded by the National Institute on Minority Health and Health Disparities. The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and HHSN 268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities, Bethesda, MD. The first author is also partially supported by Intermural Program of National Human Genomics Institute, NIH, Bethesda, MD. NR 63 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2015 VL 4 IS 6 AR e001553 DI 10.1161/JAHA.114.001553 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL5TV UT WOS:000357025100008 PM 26019130 ER PT J AU Yao, H Kim, S Chen, MH Ibrahim, JG Shah, AK Lin, JX AF Yao, Hui Kim, Sungduk Chen, Ming-Hui Ibrahim, Joseph G. Shah, Arvind K. Lin, Jianxin TI Bayesian Inference for Multivariate Meta-Regression With a Partially Observed Within-Study Sample Covariance Matrix SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Aggregate covariates; Heterogeneity; Multiple trials; Normal regression models; Random effects; Variable selection ID RANDOM-EFFECTS METAANALYSIS; MULTIPLE OUTCOMES; MODELS AB Multivariate meta-regression models are commonly used in settings where the response variable is naturally multidimensional. Such settings are common in cardiovascular and diabetes studies where the goal is to study cholesterol levels once a certain medication is given. In this setting, the natural multivariate endpoint is low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) (LDL-C, HDL-C, TG). In this article, we examine study level (aggregate) multivariate meta-data from 26 Merck sponsored double-blind, randomized, active, or placebo-controlled clinical trials on adult patients with primary hypercholesterolemia. Our goal is to develop a methodology for carrying out Bayesian inference for multivariate meta-regression models with study level data when the within-study sample covariance matrix S for the multivariate response data is partially observed. Specifically, the proposed methodology is based on postulating a multivariate random effects regression model with an unknown within-study covariance matrix Sigma in which we treat the within-study sample correlations as missing data, the standard deviations of the within-study sample covariance matrix S are assumed observed, and given Sigma, S follows a Wishart distribution. Thus, we treat the off-diagonal elements of S as missing data, and these missing elements are sampled from the appropriate full conditional distribution in a Markov chain Monte Carlo (MCMC) sampling scheme via a novel transformation based on partial correlations. We further propose several structures (models) for Sigma, which allow for borrowing strength across different treatment arms and trials. The proposed methodology is assessed using simulated as well as real data, and the results are shown to be quite promising. Supplementary materials for this article are available online. C1 [Yao, Hui] Ernst & Young, Financial Serv Off, New York, NY 10036 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Kim, Sungduk] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, Rockville, MD 20852 USA. [Ibrahim, Joseph G.] Univ N Carolina, Dept Stat, Chapel Hill, NC 27599 USA. [Shah, Arvind K.; Lin, Jianxin] Merck Res Labs, Clin Biostat, Rahway, NJ 07065 USA. RP Yao, H (reprint author), Ernst & Young, Financial Serv Off, New York, NY 10036 USA. EM hui.yao@ey.com; kims2@mail.nih.gov; ming-hui.chen@uconn.edu; ibrahim@bios.unc.edu; jianxinlin@merck.com FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH [GM 70335, CA 74015] FX The authors thank the editor, the associate editor, and the anonymous reviewer for their very helpful comments and suggestions that have led to a much improved version of the article. Dr. Kim's research was supported by the Intramural Research Program of National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Chen and Dr. Ibrahim's research was partially supported by NIH grants #GM 70335 and #CA 74015. NR 24 TC 0 Z9 0 U1 1 U2 6 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 2015 VL 110 IS 510 BP 528 EP 544 DI 10.1080/01621459.2015.1006065 PG 17 WC Statistics & Probability SC Mathematics GA CM1JN UT WOS:000357437300006 PM 26257452 ER PT J AU Josse, R Zhang, YW Giroux, V Ghosh, AK Luo, J Pommier, Y AF Josse, Rozenn Zhang, Yong-Wei Giroux, Valentin Ghosh, Arun K. Luo, Ji Pommier, Yves TI Activation of RAF1 (c-RAF) by the Marine Alkaloid Lasonolide A Induces Rapid Premature Chromosome Condensation SO MARINE DRUGS LA English DT Article DE chromosome condensation; c-raf; lasonolide A; shRNA; myosin phosphatase ID CANCER-CELLS; SERINE 338; KINASE; MITOSIS; PHOSPHATASE; PHOSPHORYLATION; (-)-LASONOLIDE; INHIBITION; MECHANISMS; MACROLIDE AB Lasonolide A (LSA), a potent antitumor polyketide from the marine sponge, Forcepia sp., induces rapid and reversible protein hyperphosphorylation and premature chromosome condensation (PCC) at nanomolar concentrations independent of cyclin-dependent kinases. To identify cellular targets of LSA, we screened 2951 shRNAs targeting a pool of human kinases and phosphatases (1140 RefSeqs) to identify genes that modulate PCC in response to LSA. This led to the identification of RAF1 (C-RAF) as a mediator of LSA-induced PCC, as shRNAs against RAF1 conferred resistance to LSA. We found that LSA induced RAF1 phosphorylation on Serine 338 within minutes in human colorectal carcinoma HCT-116, ovarian carcinoma OVCAR-8, and Burkitt's lymphoma CA46 cell lines. RAF1 depletion by siRNAs attenuated LSA-induced PCC in HCT-116 and OVCAR-8 cells. Furthermore, mouse embryonic fibroblasts (MEF) with homozygous deletion in Raf1, but not deletion in the related kinase Braf, were resistant to LSA-induced PCC. Complementation of Raf1(-/-) MEFs with wild-type human RAF1, but not with kinase-dead RAF1 mutant, restored LSA-induced PCC. Finally, the Raf inhibitor sorafenib, but not the MEK inhibitor AZD6244, effectively suppressed LSA-induced PCC. Our findings implicate a previously unknown, MAPK-independent role of RAF1 in chromatin condensation and potent activation of this pathway by LSA. C1 [Josse, Rozenn; Zhang, Yong-Wei; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Josse, Rozenn; Zhang, Yong-Wei; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Giroux, Valentin; Luo, Ji] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. RP Luo, J (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM rozenn.josse@gmail.com; yongwei.zhang@georgetown.edu; valentin_giroux@hotmail.com; akghosh@purdue.edu; ji.luo@nih.gov; pommier@nih.gov FU National Cancer Institute, Center for Cancer Research [Z01-BC-006150] FX We would like to thank Manuela Baccarini for providing the MEFs (WT, Raf1-/- and Braf). Our studies are supported by the Intramural Program of the National Cancer Institute, Center for Cancer Research (Z01-BC-006150). NR 41 TC 2 Z9 2 U1 1 U2 8 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD JUN PY 2015 VL 13 IS 6 BP 3625 EP 3639 DI 10.3390/md13063625 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CL9EZ UT WOS:000357279900022 PM 26058013 ER PT J AU Bourne, PE Brenner, SE Eisen, MB AF Bourne, Philip E. Brenner, Steven E. Eisen, Michael B. TI Ten Years of PLoS(double dagger) Computational Biology: A Decade of Appreciation and Innovation SO PLOS COMPUTATIONAL BIOLOGY LA English DT Editorial Material C1 [Bourne, Philip E.] NIH, Off Director, Bethesda, MD 20892 USA. [Brenner, Steven E.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. [Brenner, Steven E.; Eisen, Michael B.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Bourne, PE (reprint author), NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA. EM philip.bourne@nih.gov; brenner@compbio.berkeley.edu; mbeisen@lbl.gov RI Brenner, Steven/A-8729-2008; OI Brenner, Steven/0000-0001-7559-6185; Eisen, Michael/0000-0002-7528-738X NR 0 TC 1 Z9 1 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JUN PY 2015 VL 11 IS 6 AR e1004317 DI 10.1371/journal.pcbi.1004317 PG 3 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CM0AH UT WOS:000357340100032 PM 26107720 ER PT J AU Ke, RA Loverdo, C Qi, HF Sun, R Lloyd-Smith, JO AF Ke, Ruian Loverdo, Claude Qi, Hangfei Sun, Ren Lloyd-Smith, James O. TI Rational Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID REPLICATION COMPLEX INHIBITOR; DRUG-RESISTANCE; GENOTYPE 1; EVOLUTIONARY DYNAMICS; ANTIVIRAL AGENTS; VIRAL DYNAMICS; IN-VITRO; ADHERENCE; DACLATASVIR; HCV AB Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensate when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design. C1 [Ke, Ruian; Loverdo, Claude; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA. [Loverdo, Claude] Univ Paris 06, CNRS, UMR 8237, LJP, Paris, France. [Qi, Hangfei; Sun, Ren] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Sun, Ren] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. [Sun, Ren] Novartis Inst BioMed Res, Dept Infect Dis, Emeryville, CA USA. [Sun, Ren] Zhejiang Univ, Hangzhou 310003, Zhejiang, Peoples R China. [Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Ke, RA (reprint author), Los Alamos Natl Lab, Theoret Biol & Biophys T6, MS K710, Los Alamos, NM USA. EM rke.work@gmail.com; jlloydsmith@ucla.edu RI Lloyd-Smith, James/K-4080-2012; OI Lloyd-Smith, James/0000-0001-7941-502X; Loverdo, Claude/0000-0002-0888-1717 FU National Science Foundation [EF-0928690]; De Logi Chair in Biological Sciences; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX This work was supported by National Science Foundation (grant number EF-0928690 to JOLS). JOLS is grateful for support from the De Logi Chair in Biological Sciences, and from the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 5 Z9 5 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JUN PY 2015 VL 11 IS 6 AR UNSP e1004040 DI 10.1371/journal.pcbi.1004040 PG 20 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CM0AH UT WOS:000357340100001 PM 26125950 ER PT J AU Mizurini, DM Aslan, JS Gomes, T Ma, DY Francischetti, IMB Monteiro, RQ AF Mizurini, Daniella M. Aslan, Jorgeane S. Gomes, Taina Ma, Dongying Francischetti, Ivo M. B. Monteiro, Robson Q. TI Salivary Thromboxane A2-Binding Proteins from Triatomine Vectors of Chagas Disease Inhibit Platelet-Mediated Neutrophil Extracellular Traps (NETs) Formation and Arterial Thrombosis SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID DEEP-VEIN THROMBOSIS; IN-VIVO; HEMATOPHAGOUS ANIMALS; AGGREGATION INHIBITOR; INNATE IMMUNITY; COAGULATION; INFLAMMATION; COLLAGEN; GLAND; MICE AB Background The saliva of blood-feeding arthropods contains a notable diversity of molecules that target the hemostatic and immune systems of the host. Dipetalodipin and triplatin are triatomine salivary proteins that exhibit high affinity binding to prostanoids, such as TXA2, thus resulting in potent inhibitory effect on platelet aggregation in vitro. It was recently demonstrated that platelet-derived TXA2 mediates the formation of neutrophil extracellular traps ( NETs), a newly recognized link between inflammation and thrombosis that promote thrombus growth and stability. Methodology/Principal Findings This study evaluated the ability of dipetalodipin and triplatin to block NETs formation in vitro. We also investigated the in vivo antithrombotic activity of TXA2 binding proteins by employing two murine models of experimental thrombosis. Remarkably, we observed that both inhibitors abolished the platelet-mediated formation of NETs in vitro. Dipetalodipin and triplatin significantly increased carotid artery occlusion time in a FeCl3-induced injury model. Treatment with TXA2-binding proteins also protected mice from lethal pulmonary thromboembolism evoked by the intravenous injection of collagen and epinephrine. Effective antithrombotic doses of dipetalodipin and triplatin did not increase blood loss, which was estimated using the tail transection method. Conclusions/Significance Salivary TXA2-binding proteins, dipetalodipin and triplatin, are capable to prevent platelet-mediated NETs formation in vitro. This ability may contribute to the antithrombotic effects in vivo. Notably, both molecules inhibit arterial thrombosis without promoting excessive bleeding. Our results provide new insight into the antihemostatic effects of TXA2-binding proteins and may have important significance in elucidating the mechanisms of saliva to avoid host's hemostatic responses and innate immune system. C1 [Mizurini, Daniella M.; Aslan, Jorgeane S.; Gomes, Taina; Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med Leopoldo de Meis, Rio De Janeiro, Brazil. [Ma, Dongying; Francischetti, Ivo M. B.] NIAID, Vector Mol Biol Sect, LMVR, NIH, Bethesda, MD 20892 USA. RP Mizurini, DM (reprint author), Univ Fed Rio de Janeiro, Inst Bioquim Med Leopoldo de Meis, Rio De Janeiro, Brazil. EM robsonqm@bioqmed.ufrj.br RI Monteiro, Robson/B-8007-2014 FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil) [478.672/2012-8]; Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil) [E-26/102.865/2012]; Division of Intramural Research of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, USA [z99ai999999] FX This study was supported by grant 478.672/2012-8 (to RQM) from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil) and grants E-26/102.865/2012 and E-26/110.195/2013 (to RQM) from Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil), and by grant z99ai999999 from the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, USA. 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 5 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JUN PY 2015 VL 9 IS 6 AR e0003869 DI 10.1371/journal.pntd.0003869 PG 16 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CM0VX UT WOS:000357398100054 PM 26110417 ER PT J AU Pigott, DM Howes, RE Wiebe, A Battle, KE Golding, N Gething, PW Dowell, SF Farag, TH Garcia, AJ Kimball, AM Krause, LK Smith, CH Brooker, SJ Kyu, HH Vos, T Murray, CJL Moyes, CL Hay, SI AF Pigott, David M. Howes, Rosalind E. Wiebe, Antoinette Battle, Katherine E. Golding, Nick Gething, Peter W. Dowell, Scott F. Farag, Tamer H. Garcia, Andres J. Kimball, Ann M. Krause, L. Kendall Smith, Craig H. Brooker, Simon J. Kyu, Hmwe H. Vos, Theo Murray, Christopher J. L. Moyes, Catherine L. Hay, Simon I. TI Prioritising Infectious Disease Mapping SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID NEGLECTED TROPICAL DISEASES; TRANSMITTED HELMINTH INFECTIONS; DENGUE VIRUS TRANSMISSION; PLASMODIUM-VIVAX; PUBLIC-HEALTH; MALARIA MAP; GEOGRAPHIC-DISTRIBUTION; GLOBAL DISTRIBUTION; AFRICA; COUNTRIES AB Background Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease (ID) mapping for public health uses. Whilst a large number of IDs show global spatial variation, comprehensive knowledge of these geographic patterns is poor. Here we use an objective method to prioritise mapping efforts to begin to address the large deficit in global disease maps currently available. Methodology/Principal Findings Automation of ID mapping requires bespoke methodological adjustments tailored to the epidemiological characteristics of different types of diseases. Diseases were therefore grouped into 33 clusters based upon taxonomic divisions and shared epidemiological characteristics. Disability-adjusted life years, derived from the Global Burden of Disease 2013 study, were used as a globally consistent metric of disease burden. A review of global health stakeholders, existing literature and national health priorities was undertaken to assess relative interest in the diseases. The clusters were ranked by combining both metrics, which identified 44 diseases of main concern within 15 principle clusters. Whilst malaria, HIV and tuberculosis were the highest priority due to their considerable burden, the high priority clusters were dominated by neglected tropical diseases and vector-borne parasites. Conclusions/Significance A quantitative, easily-updated and flexible framework for prioritising diseases is presented here. The study identifies a possible future strategy for those diseases where significant knowledge gaps remain, as well as recognising those where global mapping programs have already made significant progress. For many conditions, potential shared epidemiological information has yet to be exploited. C1 [Pigott, David M.; Howes, Rosalind E.; Wiebe, Antoinette; Battle, Katherine E.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. [Golding, Nick; Moyes, Catherine L.; Hay, Simon I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 3PS, England. [Dowell, Scott F.; Farag, Tamer H.; Garcia, Andres J.; Kimball, Ann M.; Krause, L. Kendall; Smith, Craig H.] Bill & Melinda Gates Fdn, Seattle, WA USA. [Brooker, Simon J.] London Sch Hyg & Trop Med, London WC1, England. [Kyu, Hmwe H.; Vos, Theo; Murray, Christopher J. L.; Hay, Simon I.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Pigott, DM (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford OX1 3PS, England. EM simon.hay@well.ox.ac.uk RI Hay, Simon/F-8967-2015; OI Hay, Simon/0000-0002-0611-7272; Moyes, Catherine/0000-0002-8028-4079; Pigott, David/0000-0002-6731-4034; Golding, Nick/0000-0001-8916-5570; Gething, Peter/0000-0001-6759-5449; Battle, Katherine/0000-0003-2401-2615 FU Bill & Melinda Gates Foundation (Global Health) [OPP1093011]; Richard Southwood Graduate Scholarship from the Department of Zoology at the University of Oxford; Wellcome Trust Senior Research Fellowship [095066, 092765]; Bill & Melinda Gates Foundation [OPP1053338, OPP1033751] FX The initial work to develop a platform that will map a range of infectious diseases is funded by the Bill & Melinda Gates Foundation (Global Health Grant Number OPP1093011), and the authors are grateful to the Surveillance and Vaccine Development team for their contribution to the prioritisation work described in this paper. DMP is funded by a Sir Richard Southwood Graduate Scholarship from the Department of Zoology at the University of Oxford; REH is financially supported by a Wellcome Trust Senior Research Fellowship to SIH (#095066) which also supports AW and KEB; NG is funded by a grant from the Bill & Melinda Gates Foundation (OPP1053338). SJB is supported by a Wellcome Trust Senior Research Fellowship (#092765) and acknowledges the support of the Bill & Melinda Gates Foundation (OPP1033751). CLM is funded by a grant from the Bill & Melinda Gates Foundation (OPP1093011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 79 TC 2 Z9 2 U1 2 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JUN PY 2015 VL 9 IS 6 AR e0003756 DI 10.1371/journal.pntd.0003756 PG 21 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CM0VX UT WOS:000357398100009 PM 26061527 ER PT J AU Adland, E Paioni, P Thobakgale, C Laker, L Mori, L Muenchhoff, M Csala, A Clapson, M Flynn, J Novelli, V Hurst, J Naidoo, V Shapiro, R Huang, KHG Frater, J Prendergast, A Prado, JG Ndung'u, T Walker, BD Carrington, M Jooste, P Goulder, PJR AF Adland, Emily Paioni, Paolo Thobakgale, Christina Laker, Leana Mori, Luisa Muenchhoff, Maximilian Csala, Anna Clapson, Margaret Flynn, Jacquie Novelli, Vas Hurst, Jacob Naidoo, Vanessa Shapiro, Roger Huang, Kuan-Hsiang Gary Frater, John Prendergast, Andrew Prado, Julia G. Ndung'u, Thumbi Walker, Bruce D. Carrington, Mary Jooste, Pieter Goulder, Philip J. R. TI Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE RESPONSE; CLASS-I ALLELES; ESCAPE MUTATIONS; SELECTION PRESSURE; IMMUNE CONTROL; GAG-PROTEASE; ANTIRETROVIRAL THERAPY; ELITE CONTROLLERS; CELL RESPONSES AB HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naive, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression. C1 [Adland, Emily; Paioni, Paolo; Muenchhoff, Maximilian; Csala, Anna; Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Pathogen Res Oxford, Oxford, England. [Thobakgale, Christina; Muenchhoff, Maximilian; Naidoo, Vanessa; Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Clapson, Margaret; Flynn, Jacquie; Novelli, Vas; Goulder, Philip J. R.] Great Ormond St Hosp Sick Children, Dept Paediat Infect Dis, London WC1N 3JH, England. [Hurst, Jacob; Huang, Kuan-Hsiang Gary; Frater, John] Univ Oxford, Oxford Martin Sch, Inst Emerging Infect, Oxford, England. [Hurst, Jacob; Huang, Kuan-Hsiang Gary; Frater, John] Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England. [Hurst, Jacob; Frater, John] Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford, England. [Shapiro, Roger] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Prendergast, Andrew] Queen Mary Univ London, Blizard Inst, Ctr Paediat, London, England. [Prendergast, Andrew] Zvitambo Inst Maternal & Child Hlth Res, Harare, Zimbabwe. [Prado, Julia G.] Inst dInvest Ciencies Salut Germans Trias & Pujol, AIDS Res Inst IrsiCaixa, Barcelona, Spain. [Ndung'u, Thumbi; Walker, Bruce D.; Carrington, Mary] MIT, MGH, Ragon Inst, Boston, MA USA. [Ndung'u, Thumbi; Walker, Bruce D.; Carrington, Mary] Harvard Univ, Boston, MA 02115 USA. [Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany. [Carrington, Mary] NCI, Ctr Canc Res, Frederick, MD 21701 USA. RP Adland, E (reprint author), Univ Oxford, Dept Paediat, Pathogen Res Oxford, Oxford, England. EM philip.goulder@paediatrics.ox.ac.uk OI Ndung'u, Thumbi/0000-0003-2962-3992 FU Wellcome Trust [WT104748MA]; South African DST/NRF Research Chairs Initiative; Victor Daitz Foundation; Howard Hughes Medical Institute; National Health institute ISCIII [MS09/00279] FX This work was funded by the Wellcome Trust (WT104748MA, PJRG). TN received additional funding from the South African DST/NRF Research Chairs Initiative, the Victor Daitz Foundation and an International Early Career Scientist Award from the Howard Hughes Medical Institute. JGP holds a Miguel Servet Contract (MS09/00279) funded by National Health institute ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 10 Z9 10 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2015 VL 11 IS 6 AR UNSP e1004954 DI 10.1371/journal.ppat.1004954 PG 26 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CM0WW UT WOS:000357400900032 PM 26076345 ER PT J AU Fusco, ML Hashiguchi, T Cassan, R Biggins, JE Murin, CD Warfield, KL Li, S Holtsberg, FW Shulenin, S Vu, H Olinger, GG Kim, DH Whaley, KJ Zeitlin, L Ward, AB Nykiforuk, C Aman, MJ Berry, J Saphire, EO AF Fusco, Marnie L. Hashiguchi, Takao Cassan, Robyn Biggins, Julia E. Murin, Charles D. Warfield, Kelly L. Li, Sheng Holtsberg, Frederick W. Shulenin, Sergey Vu, Hong Olinger, Gene G. Kim, Do H. Whaley, Kevin J. Zeitlin, Larry Ward, Andrew B. Nykiforuk, Cory Aman, M. Javad Berry, Jody Saphire, Erica Ollmann TI Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs SO PLOS PATHOGENS LA English DT Article ID NIEMANN-PICK C1; EBOLA-VIRUS; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; RECEPTOR-BINDING; RHESUS MACAQUES; GLYCOPROTEIN; ANTIBODIES; INFECTION; DISEASE AB The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel "wing" feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV. C1 [Fusco, Marnie L.; Hashiguchi, Takao; Murin, Charles D.; Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Hashiguchi, Takao] Kyushu Univ, Fac Med, Dept Virol, Fukuoka 812, Japan. [Cassan, Robyn; Nykiforuk, Cory; Berry, Jody] Emergent BioSolut, Winnipeg, MB, Canada. [Biggins, Julia E.; Olinger, Gene G.] US Army Res Inst Infect Dis, Div Virol, Ft Detrick, MD USA. [Biggins, Julia E.; Warfield, Kelly L.; Holtsberg, Frederick W.; Shulenin, Sergey; Vu, Hong; Aman, M. Javad] Integrated Biotherapeut Inc, Gaithersburg, MD USA. [Murin, Charles D.; Ward, Andrew B.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Li, Sheng] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Olinger, Gene G.] NIAID, Integrated Res Facil, NIH, Frederick, MD USA. [Kim, Do H.; Whaley, Kevin J.; Zeitlin, Larry] Mapp Biopharmaceut Inc, San Diego, CA USA. [Saphire, Erica Ollmann] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Fusco, ML (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM erica@scripps.edu RI Ward, Andrew/F-9203-2014 OI Ward, Andrew/0000-0001-7153-3769 FU Center of Excellence in Translational Research [R01 AI089498, U19 AI109762]; NSF; JSPS; Uehara Memorial Foundation; Investigators in the Pathogenesis of Infectious Disease award from The Burroughs Wellcome Fund; [U01AI082156]; [R43 AI082744] FX The authors gratefully acknowledge R01 AI089498 (EOS, CN, KLW, MJA, HV, SS and JB), U19 AI109762 "Center of Excellence in Translational Research" (EOS, ABW, CN), U01AI082156 (EOS), R43 AI082744 (LZ, DHK, and KJW), NSF predoctoral fellowship (CDM), JSPS Postdoctoral Fellowships for Research Abroad (TH), Research Fellowship of The Uehara Memorial Foundation (TH), and an Investigators in the Pathogenesis of Infectious Disease award from The Burroughs Wellcome Fund (EOS) for support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 5 Z9 5 U1 4 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2015 VL 11 IS 6 AR e1005016 DI 10.1371/journal.ppat.1005016 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CM0WW UT WOS:000357400900066 PM 26115029 ER PT J AU Orru, CD Groveman, BR Raymond, LD Hughson, AG Nonno, R Zou, WQ Ghetti, B Gambetti, P Caughey, B AF Orru, Christina D. Groveman, Bradley R. Raymond, Lynne D. Hughson, Andrew G. Nonno, Romolo Zou, Wenquan Ghetti, Bernardino Gambetti, Pierluigi Caughey, Byron TI Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains SO PLOS PATHOGENS LA English DT Article ID QUAKING-INDUCED CONVERSION; CREUTZFELDT-JAKOB-DISEASE; CHRONIC WASTING DISEASE; CEREBROSPINAL-FLUID; SEEDED CONVERSION; DIFFERENT CONFORMATIONS; SEEDING ACTIVITY; RESISTANT FORMS; PRP AMYLOIDS; SCRAPIE AB Prions propagate as multiple strains in a wide variety of mammalian species. The detection of all such strains by a single ultrasensitive assay such as Real Time Quaking-induced Conversion (RT-QuIC) would facilitate prion disease diagnosis, surveillance and research. Previous studies have shown that bank voles, and transgenic mice expressing bank vole prion protein, are susceptible to most, if not all, types of prions. Here we show that bacterially expressed recombinant bank vole prion protein (residues 23-230) is an effective substrate for the sensitive RT-QuIC detection of all of the different prion types that we have tested so far - a total of 28 from humans, cattle, sheep, cervids and rodents, including several that have previously been undetectable by RT-QuIC or Protein Misfolding Cyclic Amplification. Furthermore, comparison of the relative abilities of different prions to seed positive RT-QuIC reactions with bank vole and not other recombinant prion proteins allowed discrimination of prion strains such as classical and atypical L-type bovine spongiform encephalopathy, classical and atypical Nor98 scrapie in sheep, and sporadic and variant Creutzfeldt-Jakob disease in humans. Comparison of protease-resistant RT-QuIC conversion products also aided strain discrimination and suggested the existence of several distinct classes of prion templates among the many strains tested. C1 [Orru, Christina D.; Groveman, Bradley R.; Raymond, Lynne D.; Hughson, Andrew G.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Nihon Univ, Hamilton, MT 59840 USA. [Nonno, Romolo] Ist Super Sanita, Dept Vet Publ Hlth & Food Safety, I-00161 Rome, Italy. [Zou, Wenquan; Gambetti, Pierluigi] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Ghetti, Bernardino] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. RP Orru, CD (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Nihon Univ, Hamilton, MT 59840 USA. EM bcaughey@nih.gov RI NONNO, ROMOLO/C-8323-2015 OI NONNO, ROMOLO/0000-0001-7556-1564 FU Intramural Research Program of the NIAID [ZIA AI001086-06]; Alliance BioSecure Research Foundation under the aegis of the Fondation pour la Recherche Medicale [FABS 201401]; [CDC 1051CK000100]; [NIH/NIADS R01 NS083687]; [NIH/NINDS P01 1AI106705-01AI] FX This study was funded in part by the Intramural Research Program of the NIAID (ZIA AI001086-06 to BC) and the Alliance BioSecure Research Foundation under the aegis of the Fondation pour la Recherche Medicale (FABS 201401; http://www.fondation-alliance-biosecure.org/new_eng/) to BC. Support was also provided by grants CDC 1051CK000100, NIH/NIADS R01 NS083687, and NIH/NINDS P01 1AI106705-01AI to PG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 20 Z9 21 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2015 VL 11 IS 6 AR e1004983 DI 10.1371/journal.ppat.1004983 PG 20 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CM0WW UT WOS:000357400900050 PM 26086786 ER PT J AU Van Doorslaer, K DeSalle, R Einstein, MH Burk, RD AF Van Doorslaer, Koenraad DeSalle, Rob Einstein, Mark H. Burk, Robert D. TI Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche SO PLOS PATHOGENS LA English DT Article ID HPV E6 PROTEINS; HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER; SEQUENCE ALIGNMENT; BINDING MOTIF; TUMOR-CELLS; DOMAIN; RISK; EXPRESSION; CARCINOGENICITY AB In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution. C1 [Van Doorslaer, Koenraad; Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [DeSalle, Rob] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA. [Einstein, Mark H.; Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA. [Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Pediat, Bronx, NY 10467 USA. RP Van Doorslaer, K (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM robert.burk@einstein.yu.edu OI Van Doorslaer, Koenraad/0000-0002-2985-0733 FU National Cancer Institute [CA78527]; Einstein-Montefiore Center for AIDS - NIH [AI-51519]; Einstein Cancer Research Center from the National Cancer Institute [P30CA013330] FX This work was supported in part by the National Cancer Institute (CA78527) (RDB), the Einstein-Montefiore Center for AIDS funded by the NIH (AI-51519) and the Einstein Cancer Research Center (P30CA013330) from the National Cancer Institute. KVD was employed by Albert Einstein College of Medicine at the time of this work. KVD is currently employed by the Division of Intramural Research, NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 4 Z9 4 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2015 VL 11 IS 6 AR e1004980 DI 10.1371/journal.ppat.1004980 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CM0WW UT WOS:000357400900049 PM 26086730 ER PT J AU Zhai, YJ Franco, LM Atmar, RL Quarles, JM Arden, N Bucasas, KL Wells, JM Nino, D Wang, XQ Zapata, GE Shaw, CA Belmont, JW Couch, RB AF Zhai, Yijie Franco, Luis M. Atmar, Robert L. Quarles, John M. Arden, Nancy Bucasas, Kristine L. Wells, Janet M. Nino, Diane Wang, Xueqing Zapata, Gladys E. Shaw, Chad A. Belmont, John W. Couch, Robert B. TI Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections - A Prospective Cohort Study SO PLOS PATHOGENS LA English DT Article ID SEASONAL INFLUENZA; NETWORK ANALYSIS; VIRUS-INFECTION; MICROARRAY DATA; BLOOD; IMMUNITY; ILLNESS; ACTIVATION; PATTERNS; ANTIBODY AB To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. C1 [Zhai, Yijie; Bucasas, Kristine L.; Shaw, Chad A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Zhai, Yijie; Wang, Xueqing; Zapata, Gladys E.; Belmont, John W.] Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Franco, Luis M.] NIAID, Lab Syst Biol, DIR, NIH, Bethesda, MD 20892 USA. [Atmar, Robert L.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Atmar, Robert L.; Wells, Janet M.; Couch, Robert B.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Quarles, John M.; Arden, Nancy] Texas A&M Univ, Syst Hlth Sci Ctr, Dept Microbial & Mol Pathogenesis, College Stn, TX USA. [Belmont, John W.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Zhai, YJ (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM jbelmont@bcm.tmc.edu FU U.S. National Institutes of Health [NO1-AI030039]; Burroughs Wellcome Fund - The Houston Laboratory; Population Science Training Program in Gene-Environment Interaction of the Brown Foundation Institute of Molecular Medicine of UT Health Medical School (BWF) [1008200]; F31-Ruth L. Kirschtein NRSA Individual Pre-doctoral Training Grant [F31AI071372-03] FX This work is supported by a contract from the U.S. National Institutes of Health (NO1-AI030039). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. YZ is supported by a training fellowship from the Burroughs Wellcome Fund - The Houston Laboratory and Population Science Training Program in Gene-Environment Interaction of the Brown Foundation Institute of Molecular Medicine of UT Health Medical School (BWF Grant No. 1008200). KLB was supported by F31-Ruth L. Kirschtein NRSA Individual Pre-doctoral Training Grant (F31AI071372-03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 8 Z9 8 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2015 VL 11 IS 6 AR e1004869 DI 10.1371/journal.ppat.1004869 PG 29 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CM0WW UT WOS:000357400900013 PM 26070066 ER PT J AU Tan, S Yao, JH Flynn, JA Yao, L Ward, MM AF Tan, Sovira Yao, Jianhua Flynn, John A. Yao, Lawrence Ward, Michael M. TI Dynamics of syndesmophyte growth in AS as measured by quantitative CT: heterogeneity within and among vertebral disc spaces SO RHEUMATOLOGY LA English DT Article DE ankylosing spondylitis; syndesmophyte; computed tomography ID ANKYLOSING-SPONDYLITIS; RADIOGRAPHIC DAMAGE; BONE-FORMATION; DISEASE; INFLAMMATION; PROGRESSION; PREDICT AB Objective. Syndesmophytes in AS typically grow slowly, but it is not known whether growth is uniform among syndesmophytes in the same intervertebral disc space (IDS) or among different IDSs in the same patient or if growth is heterogeneous. We examined the dynamics of syndesmophyte growth over 24 months using CT, with the main aim of determining if syndesmophytes in the same IDS or the same patient grow at similar rates. Methods. We performed lumbar spine CT scans on 33 patients and measured syndesmophytes in four IDSs using a validated computer algorithm. Scans were done at baseline and 12 and 24 months. We compared absolute and percentage changes in volume from baseline to 12 months and to 24 months among syndesmophytes in the same IDS and among four IDSs of each patient. We also examined whether growth among all IDSs differed between study years. Results. Among 60 IDSs with at least two syndesmophytes at baseline (range 2-6), there was substantial heterogeneity in both absolute (P < 0.0001) and percentage (P = 0.0002) volume increases among syndesmophytes in the same IDS. Several IDSs had both syndesmophytes with no growth and syndesmophytes that increased by > 100 mm(3). Similarly there was significant heterogeneity in syndesmophyte growth among IDSs of individual patients. Increases in total syndesmophyte volume for each patient also tended to differ between study years (P = 0.07). Conclusion. Syndesmophytes in AS do not all grow continuously. Rates of growth over 24 months commonly differ between syndesmophytes in the same IDS and between different IDSs in the same patient, suggesting that local factors regulate syndesmophyte growth. C1 [Tan, Sovira; Ward, Michael M.] NIAMSD, Bethesda, MD 20892 USA. [Yao, Jianhua; Yao, Lawrence] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Flynn, John A.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. RP Ward, MM (reprint author), NIAMSD, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases; Clinical Center, NIH; Johns Hopkins University School of Medicine General Clinical Research Center from the National Center for Research Resources/NIH [M01-RR00052] FX Funding: This work was supported by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases and by the Clinical Center, NIH, and the Johns Hopkins University School of Medicine General Clinical Research Center (grant number M01-RR00052 from the National Center for Research Resources/NIH). NR 22 TC 0 Z9 0 U1 4 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD JUN PY 2015 VL 54 IS 6 BP 972 EP 980 DI 10.1093/rheumatology/keu423 PG 9 WC Rheumatology SC Rheumatology GA CM1GP UT WOS:000357429600004 PM 25394620 ER PT J AU Cates, AM Holden, VI Myers, EM Smith, CK Kaplan, MJ Kahlenberg, JM AF Cates, Alyssa M. Holden, Victoria I. Myers, Emily M. Smith, Carolyne K. Kaplan, Mariana J. Kahlenberg, J. Michelle TI Interleukin 10 hampers endothelial cell differentiation and enhances the effects of interferon alpha on lupus endothelial cell progenitors SO RHEUMATOLOGY LA English DT Article DE IL-10; cardiovascular; lupus; endothelial progenitor; interferon alpha ID INFLAMMASOME ACTIVATION; VASCULAR REPAIR; ERYTHEMATOSUS; ATHEROSCLEROSIS; NUMBER; IL-10; VASCULOGENESIS; DYSFUNCTION; RESPONSES; DISEASE AB Objective. SLE is an autoimmune disease characterized by autoantibody generation, organ damage and an increased risk of cardiovascular disease. Generally considered an anti-inflammatory cytokine, IL-10 is increased in SLE and correlates with poor cardiovascular outcomes in the general population. The aim of this study was to explore the putative role of IL-10 in modulating endothelial function in SLE by examining the effects of this cytokine on endothelial progenitor cell/circulating angiogenic cell (EPC/CAC) differentiation. Methods. Human and murine control and lupus EPCs/CACs were differentiated into mature endothelial cells (ECs) in the presence or absence of graded concentrations of recombinant IL-10 with or without recombinant IFN-alpha or a neutralizing antibody to IL-10. IL-10-deficient mice were examined to assess the role of this cytokine in type I IFN-mediated inhibition of EC differentiation and neo-angiogenesis using an in vivo Matrigel plug assay. Serum IL-10 concentrations were measured via ELISA. Results. IL-10 hampers EC differentiation in a dose-dependent manner. In murine EPC cultures, IL-10 is required to observe the inhibitory effects of type I IFNs on EPC function and neo-angiogenesis. In human SLE EPC/CAC cultures, neutralization of IL-10 significantly improved the differentiation of EPCs, and IL-10 enhanced type I IFN-mediated EPC/CAC dysfunction. The presence of IL-10 in serum inversely correlated with EPC/CAC function in SLE but not in control cells. Conclusion. IL-10 interferes with endothelial differentiation and may enhance the effects of type I IFN on vascular repair in SLE. IL-10 may be a relevant target for improving cardiovascular risk in SLE. C1 [Cates, Alyssa M.; Myers, Emily M.; Kahlenberg, J. Michelle] Univ Michigan, Dept Internal Med, Div Rheumatol, Ann Arbor, MI 48109 USA. [Holden, Victoria I.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Smith, Carolyne K.; Kaplan, Mariana J.] NIAMSD, NIH, Syst Autoimmun Branch, Intramural Res Program, Bethesda, MD 20892 USA. RP Kahlenberg, JM (reprint author), Univ Michigan, Dept Internal Med, Div Rheumatol, 1150 W Med Ctr Dr,A520A MRSB1, Ann Arbor, MI 48109 USA. EM mkahlenb@med.umich.edu FU Alliance for Lupus Research; ACR Rheumatology Research Foundation Physician Scientist Development Award FX Funding: This work was supported by the Alliance for Lupus Research (to M.J.K.) and the ACR Rheumatology Research Foundation Physician Scientist Development Award (to J.M.K.). NR 30 TC 5 Z9 5 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD JUN PY 2015 VL 54 IS 6 BP 1114 EP 1123 DI 10.1093/rheumatology/keu431 PG 10 WC Rheumatology SC Rheumatology GA CM1GP UT WOS:000357429600021 PM 25416712 ER PT J AU Vilar, E Stoffel, E Lim, R Lynch, P You, YN Lipkin, S Vornik, L Lee, J Perloff, M Brown, P AF Vilar, E. Stoffel, E. Lim, R. Lynch, P. You, Y. N. Lipkin, S. Vornik, L. Lee, J. Perloff, M. Brown, P. TI A Phase Ib Biomarker Trial of Naproxen in Patients at Risk for DNA Mismatch Repair Deficient Colorectal Cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT ESMO 17th World Congress on Gastrointestinal Cancer CY JUL 01-04, 2015 CL Barcelona, SPAIN SP ESMO C1 [Vilar, E.] UT MD Anderson Canc Ctr, Houston, TX USA. [Stoffel, E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Lim, R.] Briham & Womens Hosp, Boston, MA USA. [Lynch, P.; You, Y. N.; Vornik, L.; Lee, J.; Brown, P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lipkin, S.] Weill Cornell Med Coll, New York, NY USA. [Perloff, M.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2015 VL 26 SU 4 MA P-305 DI 10.1093/annonc/mdv233.302 PG 1 WC Oncology SC Oncology GA CL6AL UT WOS:000357047400149 ER PT J AU Ren, BH Azzegagh, Z Jaramillo, AM Zhu, YX Pardo-Saganta, A Bagirzadeh, R Flores, JR Han, W Tang, YJ Tu, J Alanis, DM Evans, CM Guindani, M Roche, PA Rajagopal, J Chen, JC Davis, CW Tuvim, MJ Dickey, BF AF Ren, Binhui Azzegagh, Zoulikha Jaramillo, Ana M. Zhu, Yunxiang Pardo-Saganta, Ana Bagirzadeh, Rustam Flores, Jose R. Han, Wei Tang, Yong-Jun Tu, Jing Alanis, Denise M. Evans, Christopher M. Guindani, Michele Roche, Paul A. Rajagopal, Jayaraj Chen, Jichao Davis, C. William Tuvim, Michael J. Dickey, Burton F. TI SNAP23 is selectively expressed in airway secretory cells and mediates baseline and stimulated mucin secretion SO BIOSCIENCE REPORTS LA English DT Article DE 23-kDa paralogue of synaptosome-associated protein of 25 kDa (SNAP23); exocytosis; mucin; mucus; secretion ID MAST-CELLS; EPITHELIAL-CELLS; PLASMA-MEMBRANE; GOBLET CELLS; MUCUS HYPERSECRETION; GRANULE EXOCYTOSIS; MOUSE MODEL; IN-VIVO; SNAP-23; SNARE AB Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23 (23-kDa paralogue of synaptosome-associated protein of 25 kDa), selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type (WT) mice at the same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated. C1 [Ren, Binhui; Azzegagh, Zoulikha; Jaramillo, Ana M.; Bagirzadeh, Rustam; Flores, Jose R.; Han, Wei; Tang, Yong-Jun; Tu, Jing; Alanis, Denise M.; Chen, Jichao; Tuvim, Michael J.; Dickey, Burton F.] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA. [Zhu, Yunxiang; Davis, C. William] Univ N Carolina, Cyst Fibrosis Res & Treatment Ctr, Chapel Hill, NC 27599 USA. [Pardo-Saganta, Ana; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Evans, Christopher M.] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. [Guindani, Michele] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Roche, Paul A.] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Dickey, BF (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA. EM bdickey@mdanderson.org RI Guindani, Michele/F-1301-2017 OI Guindani, Michele/0000-0002-6363-9907 FU National Institutes of Health [R01HL097000, R01 HL080396, R21 ES023384]; MD Anderson Cancer Center Support Grant [CA16672]; Cystic Fibrosis Foundation [DICKE08G0, DAVIS08G0]; National Natural Science Foundation of China [81302013]; Intramural Research Program of the National Cancer Institute FX This study was supported by the National Institutes of Health [grant numbers R01HL097000 (to Y.X., M.J.T., C.W.D. and B.F.D.), R01 HL080396 and R21 ES023384 (to C.M.E.)] the MD Anderson Cancer Center Support Grant [grant number CA16672]; the Cystic Fibrosis Foundation [grant number DICKE08G0 (to M.J.T. and B.F.D.) and DAVIS08G0 (to C.W.D.)]; the National Natural Science Foundation of China [grant number 81302013 (to B.R.)]; and the Intramural Research Program of the National Cancer Institute (P.A.R.). NR 51 TC 0 Z9 0 U1 2 U2 4 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0144-8463 EI 1573-4935 J9 BIOSCIENCE REP JI Biosci. Rep. PD JUN 1 PY 2015 VL 35 AR e00220 DI 10.1042/BSR20150004 PN 3 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CL6VM UT WOS:000357105800029 ER PT J AU Katzel, JA Merchant, M Chaturvedi, AK Silverberg, MJ AF Katzel, Jed A. Merchant, Maqdooda Chaturvedi, Anil K. Silverberg, Michael J. TI Contribution of Demographic and Behavioral Factors on the Changing Incidence Rates of Oropharyngeal and Oral Cavity Cancers in Northern California SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS INFECTION; UNITED-STATES; NECK-CANCER; SMOKING PREVALENCE; INCIDENCE TRENDS; TONGUE CANCER; YOUNG-ADULTS; RISK-FACTOR; HEAD AB Background: It is unknown to what extent patient demographics, smoking, and alcohol use have contributed to changes in oropharyngeal and oral cavity cancer incidence rates. Methods: We performed a cohort study of Kaiser Permanente healthplan members, ages 20 to 89, for years 1995-2010 (n = 2.2 million annual members). Poisson Regression models estimated calendar trends in cancer rates both adjusted for and stratified by age, sex, smoking, and alcohol abuse history. Results: We identified 1,383 human papillomavirus (HPV)-related and 1,344 HPV-unrelated oral cavity and oropharyngeal cancer cases. With adjustment for age and sex, HPV-related cancer incidence rates increased 3.8% per year (P < 0.001) between 1995 and 2010, whereas rates for HPV-unrelated cancers decreased 2.4% per year (P < 0.001). For years 2007 to 2010, with additional adjustment for smoking and alcohol abuse, results were nonsignificant, but similar in magnitude. The increasing rates for HPV-related cancers were more prominent among nonsmokers (+14.5%) compared with smokers (-2.5%; P-interaction = 0.058). The decreased rates for HPV-unrelated sites were more prominent among those >= 60 years (-11.0%) compared with those < 60 years (+16.8%; P-interaction = 0.006), among smokers (-9.7%) compared with nonsmokers (+8.4%; P-interaction = 0.055), and among those with an alcohol abuse history (-20.4%) compared with those without a history (+5.8%; P-interaction = 0.009). Conclusions: The observed increasing HPV-related cancer rates are most evident among nonsmokers, whereas the decreasing HPV-unrelated cancer rates are least evident among younger individuals, nonsmokers, and those without an alcohol abuse history. Impact: Continued vigilance for oropharyngeal and oral cavity cancer is warranted, including among those without traditional risk factors such as smoking and alcohol abuse. (C)2015 AACR. C1 [Katzel, Jed A.] Kaiser Permanente, Dept Oncol, Santa Clara, CA USA. [Merchant, Maqdooda; Silverberg, Michael J.] Kaiser Permanente, Div Res, Oakland, CA USA. [Chaturvedi, Anil K.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Katzel, JA (reprint author), Kaiser Permanente Santa Clara Med Ctr, 710 Lawrence Expressway,Dept 440, Santa Clara, CA 95051 USA. EM jed.a.katzel@kp.org RI Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU Pfizer; Merck FX M.J. Silverberg reports receiving a commercial research grant from Pfizer and Merck. No potential conflicts of interest were disclosed by the other authors. NR 48 TC 1 Z9 1 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2015 VL 24 IS 6 BP 978 EP 984 DI 10.1158/1055-9965.EPI-14-1416 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CM1FB UT WOS:000357425200012 PM 25956592 ER PT J AU Goodson, WH Lowe, L Carpenter, DO Gilbertson, M Ali, AM Salsamendi, ALD Lasfar, A Carnero, A Azqueta, A Amedei, A Charles, AK Collins, AR Ward, A Salzberg, AC Colacci, A Olsen, AK Berg, A Barclay, BJ Zhou, BHP Blanco-Aparicio, C Baglole, CJ Dong, CF Mondello, C Hsu, CW Naus, CC Yedjou, C Curran, CS Laird, DW Koch, DC Carlin, DJ Felsher, DW Roy, D Brown, DG Ratovitski, E Ryan, EP Corsini, E Rojas, E Moon, EY Laconi, E Marongiu, F Al-Mulla, F Chiaradonna, F Darroudi, F Martin, FL Van Schooten, FJ Goldberg, GS Wagemaker, G Nangami, G Calaf, GM Williams, G Wolf, GT Koppen, G Brunborg, G Lyerly, HK Krishnan, H Ab Hamid, H Yasaei, H Sone, H Kondoh, H Salem, HK Hsu, HY Park, HH Koturbash, I Miousse, IR Scovassi, AI Klaunig, JE Vondracek, J Raju, J Roman, J Wise, JP Whitfield, JR Woodrick, J Christopher, JA Ochieng, J Martinez-Leal, JF Weisz, J Kravchenko, J Sun, J Prudhomme, KR Narayanan, KB Cohen-Solal, KA Moorwood, K Gonzalez, L Soucek, L Jian, L D'Abronzo, LS Lin, LT Li, L Gulliver, L McCawley, LJ Memeo, L Vermeulen, L Leyns, L Zhang, LP Valverde, M Khatami, M Romano, MF Chapellier, M Williams, MA Wade, M Manjili, MH Lleonart, M Xia, MH Gonzalez, MJ Karamouzis, MV Kirsch-Volders, M Vaccari, M Kuemmerle, NB Singh, N Cruickshanks, N Kleinstreuer, N van Larebeke, N Ahmed, N Ogunkua, O Krishnakumar, PK Vadgama, P Marignani, PA Ghosh, PM Ostrosky-Wegman, P Thompson, P Dent, P Heneberg, P Darbre, P Leung, PS Nangia-Makker, P Cheng, Q Robey, RB Al-Temaimi, R Roy, R Andrade-Vieira, R Sinha, RK Mehta, R Vento, R Di Fiore, R Ponce-Cusi, R Dornetshuber-Fleiss, R Nahta, R Castellino, RC Palorini, R Abd Hamid, R Langie, SAS Eltom, S Brooks, SA Ryeom, S Wise, SS Bay, SN Harris, SA Papagerakis, S Romano, S Pavanello, S Eriksson, S Forte, S Casey, SC Luanpitpong, S Lee, TJ Otsuki, T Chen, T Massfelder, T Sanderson, T Guarnieri, T Hultman, T Dormoy, V Odero-Marah, V Sabbisetti, V Maguer-Satta, V Rathmell, WK Engstrom, W Decker, WK Bisson, WH Rojanasakul, Y Luqmani, Y Chen, ZB Hu, ZW AF Goodson, William H., III Lowe, Leroy Carpenter, David O. Gilbertson, Michael Ali, Abdul Manaf de Cerain Salsamendi, Adela Lopez Lasfar, Ahmed Carnero, Amancio Azqueta, Amaya Amedei, Amedeo Charles, Amelia K. Collins, Andrew R. Ward, Andrew Salzberg, Anna C. Colacci, Annamaria Olsen, Ann-Karin Berg, Arthur Barclay, Barry J. Zhou, Binhua P. Blanco-Aparicio, Carmen Baglole, Carolyn J. Dong, Chenfang Mondello, Chiara Hsu, Chia-Wen Naus, Christian C. Yedjou, Clement Curran, Colleen S. Laird, Dale W. Koch, Daniel C. Carlin, Danielle J. Felsher, Dean W. Roy, Debasish Brown, Dustin G. Ratovitski, Edward Ryan, Elizabeth P. Corsini, Emanuela Rojas, Emilio Moon, Eun-Yi Laconi, Ezio Marongiu, Fabio Al-Mulla, Fahd Chiaradonna, Ferdinando Darroudi, Firouz Martin, Francis L. Van Schooten, Frederik J. Goldberg, Gary S. Wagemaker, Gerard Nangami, Gladys Calaf, Gloria M. Williams, Graeme Wolf, Gregory T. Koppen, Gudrun Brunborg, Gunnar Lyerly, H. Kim Krishnan, Harini Ab Hamid, Hasiah Yasaei, Hemad Sone, Hideko Kondoh, Hiroshi Salem, Hosni K. Hsu, Hsue-Yin Park, Hyun Ho Koturbash, Igor Miousse, Isabelle R. Scovassi, A. Ivana Klaunig, James E. Vondracek, Jan Raju, Jayadev Roman, Jesse Wise, John Pierce, Sr. Whitfield, Jonathan R. Woodrick, Jordan Christopher, Joseph A. Ochieng, Josiah Fernando Martinez-Leal, Juan Weisz, Judith Kravchenko, Julia Sun, Jun Prudhomme, Kalan R. Narayanan, Kannan Badri Cohen-Solal, Karine A. Moorwood, Kim Gonzalez, Laetitia Soucek, Laura Jian, Le D'Abronzo, Leandro S. Lin, Liang-Tzung Li, Lin Gulliver, Linda McCawley, Lisa J. Memeo, Lorenzo Vermeulen, Louis Leyns, Luc Zhang, Luoping Valverde, Mahara Khatami, Mahin Romano, Maria Fiammetta Chapellier, Marion Williams, Marc A. Wade, Mark Manjili, Masoud H. Lleonart, Matilde Xia, Menghang Gonzalez, Michael J. Karamouzis, Michalis V. Kirsch-Volders, Micheline Vaccari, Monica Kuemmerle, Nancy B. Singh, Neetu Cruickshanks, Nichola Kleinstreuer, Nicole van Larebeke, Nik Ahmed, Nuzhat Ogunkua, Olugbemiga Krishnakumar, P. K. Vadgama, Pankaj Marignani, Paola A. Ghosh, Paramita M. Ostrosky-Wegman, Patricia Thompson, Patricia Dent, Paul Heneberg, Petr Darbre, Philippa Leung, Po Sing Nangia-Makker, Pratima Cheng, Qiang (Shawn) Robey, R. Brooks Al-Temaimi, Rabeah Roy, Rabindra Andrade-Vieira, Rafaela Sinha, Ranjeet K. Mehta, Rekha Vento, Renza Di Fiore, Riccardo Ponce-Cusi, Richard Dornetshuber-Fleiss, Rita Nahta, Rita Castellino, Robert C. Palorini, Roberta Abd Hamid, Roslida Langie, Sabine A. S. Eltom, Sakina Brooks, Samira A. Ryeom, Sandra Wise, Sandra S. Bay, Sarah N. Harris, Shelley A. Papagerakis, Silvana Romano, Simona Pavanello, Sofia Eriksson, Staffan Forte, Stefano Casey, Stephanie C. Luanpitpong, Sudjit Lee, Tae-Jin Otsuki, Takemi Chen, Tao Massfelder, Thierry Sanderson, Thomas Guarnieri, Tiziana Hultman, Tove Dormoy, Valerian Odero-Marah, Valerie Sabbisetti, Venkata Maguer-Satta, Veronique Rathmell, W. Kimryn Engstrom, Wilhelm Decker, William K. Bisson, William H. Rojanasakul, Yon Luqmani, Yunus Chen, Zhenbang Hu, Zhiwei TI Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead SO CARCINOGENESIS LA English DT Review ID BREAST-CANCER CELLS; ESTROGEN-RECEPTOR-ALPHA; EPITHELIAL-MESENCHYMAL TRANSITION; VASCULAR ENDOTHELIAL-CELLS; ARYL-HYDROCARBON RECEPTOR; ACTIVATED PROTEIN-KINASES; POLYBROMINATED DIPHENYL ETHERS; ENDOCRINE-DISRUPTING CHEMICALS; BISPHENOL-A EXPOSURE; SPRAGUE-DAWLEY RATS AB Low-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated.Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. C1 [Goodson, William H., III] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94115 USA. [Lowe, Leroy] Getting Know Canc, Truro, NS B2N 1X5, Canada. [Lowe, Leroy; Martin, Francis L.] Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4AP, England. [Gilbertson, Michael] Getting Know Canc, Guelph, ON N1G 1E4, Canada. [Ali, Abdul Manaf] Sultan Zainal Abidin Univ, Sch Biotechnol, Fac Agr Biotechnol & Food Sci, Besut 22200, Terengganu, Malaysia. [de Cerain Salsamendi, Adela Lopez; Azqueta, Amaya] Univ Navarra, Dept Pharmacol & Toxicol, Fac Pharm, Pamplona 31008, Spain. [Lasfar, Ahmed] Rutgers State Univ, Dept Pharmacol & Toxicol, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA. [Carnero, Amancio] Univ Seville, Inst Biomed Sevilla, Consejo Super Invest Cient, Hosp Univ Virgen Rocio, Seville 41013, Spain. [Amedei, Amedeo] Univ Florence, Dept Expt & Clin Med, I-50134 Florence, Italy. [Charles, Amelia K.] Univ Reading, Sch Biol Sci, Reading RG6 6UB, Berks, England. [Collins, Andrew R.] Univ Oslo, Dept Nutr, Oslo, Norway. [Ward, Andrew; Moorwood, Kim] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. [Salzberg, Anna C.; Berg, Arthur] Penn State Univ, Dept Publ Hlth Sci, Coll Med, Hershey, PA 17033 USA. [Colacci, Annamaria; Vaccari, Monica] Environm Protect & Hlth Prevent Agcy, Ctr Environm Carcinogenesis & Risk Assessment, I-40126 Bologna, Italy. [Olsen, Ann-Karin; Brunborg, Gunnar] Norwegian Inst Publ Hlth, Div Environm Med, Dept Chem & Radiat, N-0403 Oslo, Norway. [Barclay, Barry J.] Planet Biotechnol Inc, St Albert, AB T8N 5K4, Canada. [Zhou, Binhua P.; Dong, Chenfang] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40508 USA. [Blanco-Aparicio, Carmen] CNIO, Spanish Natl Canc Res Ctr, Madrid 28029, Spain. [Baglole, Carolyn J.] McGill Univ, Dept Med, Montreal, PQ H4A 3J1, Canada. [Mondello, Chiara; Scovassi, A. Ivana] CNR, Ist Genet Mol, I-27100 Pavia, Italy. [Hsu, Chia-Wen; Xia, Menghang] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Naus, Christian C.] Univ British Columbia, Dept Cellular & Physiol Sci, Inst Life Sci, Fac Med, Vancouver, BC V5Z 1M9, Canada. [Yedjou, Clement] Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. [Curran, Colleen S.] Univ Wisconsin, Dept Mol & Environm Toxicol, Madison, WI 53706 USA. [Laird, Dale W.] Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 3K7, Canada. [Koch, Daniel C.; Casey, Stephanie C.] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Carlin, Danielle J.] NIEHS, Superfund Res Program, Res Triangle Pk, NC 27560 USA. [Felsher, Dean W.] Stanford Univ, Dept Med Oncol & Pathol, Stanford, CA 94305 USA. [Roy, Debasish] CUNY, Dept Nat Sci, Bronx, NY 10451 USA. [Brown, Dustin G.; Ryan, Elizabeth P.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. [Ratovitski, Edward] Johns Hopkins Univ, Sch Med, Dept Head & Neck Surg Head & Neck Canc Res, Baltimore, MD 21205 USA. [Corsini, Emanuela] Univ Milan, Dept Pharmacol & Biomol Sci, I-20133 Milan, Italy. [Rojas, Emilio; Valverde, Mahara; Ostrosky-Wegman, Patricia] Univ Nacl Autonoma Mexico, Inst Biomed Res, Dept Genom Med & Environm Toxicol, Mexico City 04510, DF, Mexico. [Moon, Eun-Yi] Sejong Univ, Dept Biosci & Biotechnol, Seoul 143747, South Korea. [Laconi, Ezio; Marongiu, Fabio] Univ Cagliari, Dept Biomed Sci, I-09124 Cagliari, Italy. [Al-Mulla, Fahd] Kuwait Univ, Dept Pathol, Safat 13110, Kuwait. [Chiaradonna, Ferdinando; Palorini, Roberta] Univ Milano Bicocca, Dept Biotechnol & Biosci, I-20126 Milan, Italy. [Chiaradonna, Ferdinando; Palorini, Roberta] Univ Milano Bicocca, Dept Biotechnol & Biosci, SYSBIO Ctr Syst Biol, I-20126 Milan, Italy. [Darroudi, Firouz] Coll North Atlantic, Human Safety & Environm Res, Dept Hlth Sci, Doha 24449, Qatar. [Van Schooten, Frederik J.] Maastricht Univ, Dept Toxicol, NUTRIM Sch Nutr Toxicol & Metab, NL-6200 Maastricht, Netherlands. [Goldberg, Gary S.; Krishnan, Harini; Hu, Zhiwei] Rowan Univ, Sch Osteopath Med, Dept Mol Biol, Stratford, NJ 08084 USA. [Wagemaker, Gerard] Hacettepe Univ, Ctr Stem Cell Res & Dev, TR-06640 Ankara, Turkey. [Nangami, Gladys; Ochieng, Josiah; Ogunkua, Olugbemiga; Eltom, Sakina; Chen, Zhenbang] Meharry Med Coll, Dept Biochem & Canc Biol, Nashville, TN 37208 USA. [Calaf, Gloria M.] Columbia Univ, Ctr Radiol Res, Med Ctr, New York, NY 10032 USA. [Calaf, Gloria M.; Ponce-Cusi, Richard] Univ Tarapaca, Inst Alta Invest, Arica, Chile. [Williams, Graeme] Univ Reading, Sch Biol Sci, Reading RG6 6UB, Berks, England. [Wolf, Gregory T.; Papagerakis, Silvana] Univ Michigan, Dept Otolaryngol Head & Neck Surg, Sch Med, Ann Arbor, MI 48109 USA. [Koppen, Gudrun; Langie, Sabine A. S.] Flemish Inst Technol Res, Environm Risk & Hlth Unit, B-2400 Mol, Belgium. [Lyerly, H. Kim; Kravchenko, Julia] Duke Univ, Med Ctr, Dept Surg, Pathol,Immunol, Durham, NC 27710 USA. [Ab Hamid, Hasiah; Abd Hamid, Roslida] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Biomed Sci, Serdang 43400, Selangor, Malaysia. [Yasaei, Hemad] Brunel Univ, Coll Hlth & Life Sci, Dept Life Sci, Uxbridge UB8 3PH, Middx, England. [Yasaei, Hemad] Brunel Univ, Inst Environm Hlth & Soc, Hlth & Environm Theme, Uxbridge UB8 3PH, Middx, England. [Sone, Hideko] Natl Inst Environm Studies, Tsukuba, Ibaraki 3058506, Japan. [Kondoh, Hiroshi] Kyoto Univ Hosp, Dept Geriatr Med, Sakyo Ku, Kyoto 6068507, Japan. [Salem, Hosni K.] Cairo Univ, Dept Urol, Kasr Al Ainy Sch Med, Cairo 11559, Egypt. [Hsu, Hsue-Yin] Tzu Chi Univ, Dept Life Sci, Hualien 970, Taiwan. [Park, Hyun Ho; Narayanan, Kannan Badri] Yeungnam Univ, Sch Biotechnol, Gyeongbuk 712749, South Korea. [Koturbash, Igor; Miousse, Isabelle R.] Univ Arkansas Med Sci, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA. [Klaunig, James E.] Indiana Univ, Dept Environm Hlth, Sch Publ Hlth, Bloomington, IN 47405 USA. [Vondracek, Jan] Acad Sci Czech Republic, Inst Biophys, Dept Cytokinet, CZ-61265 Brno, Czech Republic. [Raju, Jayadev; Mehta, Rekha] Hlth Canada, Regulatory Toxicol Res Div, Bur Chem Safety, Food Directorate, Ottawa, ON K1A 0K9, Canada. [Roman, Jesse] Univ Louisville, Dept Med, Louisville, KY 40202 USA. [Roman, Jesse] Robley Rex VA Med Ctr, Louisville, KY 40202 USA. [Wise, John Pierce, Sr.; Wise, Sandra S.] Univ So Maine, Dept Appl Sci Med, Portland, ME 04104 USA. [Whitfield, Jonathan R.; Soucek, Laura] Vall dHebron Inst Oncol VHIO, Mouse Models Canc Therapies Grp, Barcelona 08035, Spain. [Woodrick, Jordan; Roy, Rabindra] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Christopher, Joseph A.] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England. [Fernando Martinez-Leal, Juan] Pharmamar SAU, Dept Cell Biol, Madrid 28770, Spain. [Weisz, Judith] Penn State Univ, Coll Med, Dept Obstet & Gynecol, Hershey, PA 17033 USA. [Weisz, Judith] Penn State Univ, Coll Med, Dept Pathol, Hershey, PA 17033 USA. [Sun, Jun] Rush Univ, Dept Biochem, Chicago, IL 60612 USA. [Prudhomme, Kalan R.; Bisson, William H.] Oregon State Univ, Environm Hlth Sci Ctr, Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Cohen-Solal, Karine A.] Rutgers Canc Inst New Jersey, Dept Med Med Oncol, New Brunswick, NJ 08903 USA. [Gonzalez, Laetitia; Leyns, Luc; Kirsch-Volders, Micheline] Vrije Univ Brussel, Lab Cell Genet, B-1050 Brussels, Belgium. [Soucek, Laura] Catalan Inst Res & Adv Studies ICREA, Barcelona 08010, Spain. [Jian, Le] Curtin Univ, Sch Publ Hlth, Bentley, WA 6102, Australia. [Jian, Le] Govt Western Australia, Dept Hlth, Publ Hlth & Clin Serv Div, Perth, WA 6004, Australia. [D'Abronzo, Leandro S.; Ghosh, Paramita M.] Univ Calif Davis, Dept Urol, Sacramento, CA 95817 USA. [Lin, Liang-Tzung] Taipei Med Univ, Sch Med, Dept Microbiol & Immunol, Coll Med, Taipei 11031, Taiwan. [Li, Lin; Leung, Po Sing] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Gulliver, Linda] Univ Otago, Fac Med, Dunedin 9054, New Zealand. [McCawley, Lisa J.] Vanderbilt Univ, Dept Biomed Engn & Canc Biol, Nashville, TN 37235 USA. [Memeo, Lorenzo; Forte, Stefano] Mediterranean Inst Oncol, Dept Expt Oncol, I-95029 Viagrande, CT, Italy. [Vermeulen, Louis] Univ Amsterdam, Acad Med Ctr, Ctr Expt Mol Med, NL-1105 AZ Amsterdam, Netherlands. [Zhang, Luoping] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Khatami, Mahin] NCI, Inflammat & Canc Res, NIH, Bethesda, MD 20892 USA. [Romano, Maria Fiammetta; Romano, Simona] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, I-80131 Naples, Italy. [Chapellier, Marion] Ctr Rech Cancerol, U1052, UMR5286, Lyon, France. [Williams, Marc A.; Maguer-Satta, Veronique] US Army, Inst Publ Hlth, Toxicol Portfolio Hlth Effects Res Program, Edgewood, MD 21010 USA. [Wade, Mark] Fdn Ist Italiano Tecnol, Ctr Genom Sci IIT SEMM, I-20139 Milan, Italy. [Manjili, Masoud H.] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Massey Canc Ctr, Richmond, VA 23298 USA. [Lleonart, Matilde] Inst Recerca Hosp Vall DHebron, Barcelona 08035, Spain. [Gonzalez, Michael J.] Univ Puerto Rico, Nutr Program, Sch Publ Hlth, San Juan, PR 00921 USA. [Karamouzis, Michalis V.] Univ Athens, Sch Med, Dept Biol Chem, Inst Mol Med & Biomed Res, Athens 10676, Greece. [Kuemmerle, Nancy B.; Robey, R. Brooks] White River Junction Vet Affairs Med Ctr, White River Jct, VT 05009 USA. [Kuemmerle, Nancy B.; Robey, R. Brooks] Geisel Sch Med Dartmouth, Hanover, NH 03755 USA. [Singh, Neetu] King Georges Med Univ, Adv Mol Sci Res Ctr, Ctr Adv Res, Lucknow 226003, Uttar Pradesh, India. [Cruickshanks, Nichola; Dent, Paul] Virginia Commonwealth Univ, Dept Neurosurg, Richmond, VA 23298 USA. [Cruickshanks, Nichola; Dent, Paul] Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23298 USA. [Cruickshanks, Nichola; Dent, Paul] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. [Kleinstreuer, Nicole] Integrated Lab Syst Inc, Support Natl Toxicol Program Interagency Ctr Eval, Res Triangle Pk, NC 27709 USA. [van Larebeke, Nik] Vrije Univ Brussel, Milieu Geochem, Analyt, B-1050 Brussels, Belgium. [Ahmed, Nuzhat] Univ Melbourne, Dept Obstet & Gynecol, Parkville, Vic 3052, Australia. [Krishnakumar, P. K.] King Fahd Univ Petr & Minerals, Res Inst, Ctr Environm & Water, Dhahran 3126, Saudi Arabia. [Vadgama, Pankaj] Queen Mary Univ London, Sch Engn & Mat Sci, London E1 4NS, England. [Marignani, Paola A.; Andrade-Vieira, Rafaela] Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS B3H 4R2, Canada. [Thompson, Patricia] SUNY Stony Brook, Stony Brook Sch Med, Dept Pathol, Stony Brook, NY 11794 USA. [Heneberg, Petr] Charles Univ Prague, Fac Med 3, CZ-10000 Prague 10, Czech Republic. [Darbre, Philippa] Univ Reading, Sch Biol Sci, Reading RG6 6UB, Berks, England. [Nangia-Makker, Pratima] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. [Cheng, Qiang (Shawn)] So Illinois Univ, Dept Comp Sci, Carbondale, IL 62901 USA. [Al-Temaimi, Rabeah] Kuwait Univ, Dept Pathol, Human Genet Unit, Fac Med, Jabriya 13110, Kuwait. [Sinha, Ranjeet K.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Vento, Renza; Di Fiore, Riccardo] Univ Palermo, Dept Biol Chem & Pharmaceut Sci & Technol, Polyclin Plexus, I-90127 Palermo, Italy. [Vento, Renza] Temple Univ, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA. [Dornetshuber-Fleiss, Rita] Univ Vienna, Dept Pharmacol & Toxicol, A-1090 Vienna, Austria. [Dornetshuber-Fleiss, Rita] Med Univ Vienna, Dept Med, Inst Canc Res, A-1090 Vienna, Austria. [Nahta, Rita] Emory Univ, Dept Pharmacol, Sch Med, Atlanta, GA 30322 USA. [Nahta, Rita] Emory Univ, Dept Hematol & Med Oncol, Sch Med, Atlanta, GA 30322 USA. [Nahta, Rita] Winship Canc Inst, Atlanta, GA 30322 USA. [Castellino, Robert C.] Childrens Healthcare Atlanta, Div Hematol & Oncol, Dept Pediat, Atlanta, GA 30322 USA. [Castellino, Robert C.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. [Brooks, Samira A.; Rathmell, W. Kimryn] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Ryeom, Sandra] Univ Penn, Dept Canc Biol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bay, Sarah N.] Emory Univ, Grad Div Biol & Biomed Sci, Program Genet & Mol Biol, Atlanta, GA 30322 USA. [Harris, Shelley A.] Canc Care Ontario, Res Prevent & Canc Control, Populat Hlth & Prevent, Toronto, ON M5G 2L7, Canada. [Harris, Shelley A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Dept Epidemiol, Toronto, ON M5T 3M7, Canada. [Harris, Shelley A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Dept Occupat & Environm Hlth, Toronto, ON M5T 3M7, Canada. [Pavanello, Sofia] Univ Padua, Unit Occupat Med, Dept Cardiac Thorac & Vasc Sci, I-35128 Padua, Italy. [Eriksson, Staffan] Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, VHC, SE-75651 Uppsala, Sweden. [Luanpitpong, Sudjit] Mahidol Univ, Fac Med, Siriraj Hosp, Siriraj Ctr Excellence Stem Cell Res, Bangkok 10700, Thailand. [Lee, Tae-Jin] Yeungnam Univ, Dept Anat, Coll Med, Daegu 705717, South Korea. [Otsuki, Takemi] Kawasaki Med Univ, Dept Hyg, Okayama 7010192, Japan. [Chen, Tao] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Massfelder, Thierry; Dormoy, Valerian] Univ Strasbourg, INSERM, Fac Med,U1113, Team Cell Signalling & Commun Kidney & Prostate C, F-67085 Strasbourg, France. [Sanderson, Thomas] Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ H7V 1B7, Canada. [Guarnieri, Tiziana] Alma Mater Studiorum Univ Bologna, Dept Biol Geol & Environm Sci, I-40126 Bologna, Italy. [Guarnieri, Tiziana] S Orsola Malpighi Univ Hosp, Ctr Appl Biomed Res, I-40126 Bologna, Italy. [Guarnieri, Tiziana] Natl Inst Biostruct & Biosyst, I-00136 Rome, Italy. [Hultman, Tove; Engstrom, Wilhelm] Swedish Univ Agr Sci, Fac Vet Med, Dept Biosci & Vet Publ Hlth, S-75007 Uppsala, Sweden. [Dormoy, Valerian] Univ Calif Irvine, Dept Cell & Dev Biol, Irvine, CA 92697 USA. [Odero-Marah, Valerie] Clark Atlanta Univ, Dept Biol, Ctr Canc Res & Therapeut Dev, Atlanta, GA 30314 USA. [Sabbisetti, Venkata] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Decker, William K.] Baylor Coll Med, Houston, TX 77030 USA. [Rojanasakul, Yon] W Virginia Univ, Dept Pharmaceut Sci, Morgantown, WV 26506 USA. [Luqmani, Yunus] Kuwait Univ, Fac Pharm, Dept Pharmaceut Chem, Safat 13110, Kuwait. [Hu, Zhiwei] Ohio State Univ, Coll Med, Dept Surg, James Comprehens Canc Ctr, Columbus, OH 43210 USA. RP Goodson, WH (reprint author), Calif Pacific Med Ctr, Res Inst, 2100 Webster St 401, San Francisco, CA 94115 USA. EM whg3md@att.net; leroy.lowe@gettingtoknowcancer.org RI Mondello, Chiara/B-8305-2015; Massfelder, Thierry/I-1260-2016; Dormoy, Valerian/P-5109-2016; Marongiu, Fabio/E-6294-2016; Robey, R. Brooks/J-7099-2013; Forte, Stefano/D-3645-2013; CHIARADONNA, Ferdinando/K-4959-2016; Vermeulen, Louis/B-7488-2008; Gonzalez, Laetitia/F-5116-2011; Leung, Po Sing/P-5758-2014; Heneberg, Petr/C-1881-2012; Vondracek, Jan/J-3037-2012; Jian, Le/B-9180-2012; Laird, Dale /E-4176-2015; Hu, Zhiwei/L-3727-2013; Wade, Mark /B-6719-2009; Lopez de Cerain, Adela/L-4572-2014; IBIS, CANCER/P-3323-2015 OI Kleinstreuer, Nicole/0000-0002-7914-3682; Nangia-Makker, Pratima/0000-0002-1917-169X; Blanco-Aparicio, Carmen/0000-0002-3249-6595; Soucek, Laura/0000-0002-4750-7971; Whitfield, Jonathan/0000-0002-4925-7283; Barclay, Barry/0000-0002-8325-115X; Mondello, Chiara/0000-0002-8379-9246; Scovassi, Anna Ivana/0000-0003-3484-9881; L Martin, Francis/0000-0001-8562-4944; Marongiu, Fabio/0000-0001-5860-4227; Robey, R. Brooks/0000-0001-5059-3965; Forte, Stefano/0000-0001-5746-7451; Roy, Debasish/0000-0001-6590-0569; Valverde, Mahara/0000-0001-6975-1185; Luanpitpong, Sudjit/0000-0002-1639-4935; CHIARADONNA, Ferdinando/0000-0001-8529-2732; Vermeulen, Louis/0000-0002-6066-789X; Gonzalez, Laetitia/0000-0003-4182-3428; Heneberg, Petr/0000-0002-0703-951X; Vondracek, Jan/0000-0003-4071-1969; Hu, Zhiwei/0000-0002-0023-1170; Wade, Mark /0000-0002-2688-5965; Lopez de Cerain, Adela/0000-0002-2085-1289; FU National Institute of Health-National Institute of Environmental Health Sciences (NIEHS) [R13ES023276]; California Breast Cancer Research Program; Clarence Heller Foundation; California Pacific Medical Center Foundation; University of Sultan Zainal Abidin, Malaysia; Rutgers Cancer Institute of New Jersey; Research Council of Norway (RCN) through its Centres of Excellence funding scheme [223268/F50]; Spanish Ministry of Economy and Competitivity, ISCIII [Fis: PI12/00137, RTICC: RD12/0036/0028]; FEDER from Regional Development European Funds (European Union); Consejeria de Ciencia e Innovacion [CTS-1848]; Consejeria de Salud of the Junta de Andalucia [PI-0306-2012]; Ministerio de Educacion y Ciencia (Juande la Cierva' programme) of the Spanish Government; Italian Ministry of University and Research [2009FZZ4XM_002]; University of Florence; University of Oslo; Emilia-Romagna Region - Project 'Supersite' in Italy; Fonds de recherche du Quebec-Sante (FRQ-S); Fondazione Cariplo in Milan, Italy [2011-0370]; National Institutes of Health (NIH-NIMHD) [G12MD007581]; Burroughs Wellcome Fund Postdoctoral Enrichment Award; Timor Biology Training grant [NIH T32CA09151]; United States Department of Health and Human Services, NIH [R01 CA170378 PQ22, RO1 CA184384, U54 CA149145, U54 CA151459, P50 CA114747, 1121 CA169964]; CONACyT [152473]; AIRC (Italian Association for Cancer Research) [IG 14640]; Sardinian Regional Government (RAS); Public Problem-Solving Program [NRF-015M3C8A6A06014500]; National Research Foundation of Korea (NRF) [2013M2B2A9A03051296, 2010-0018545]; Ministry of Education, Science and Technology (MEST) in Korea; Kuwait Foundation for the Advancement of Sciences [2011-1302-06]; SysBioNet, a grant for the Italian Roadmap of European Strategy Forum on Research Infrastructures (ESFRI); AIRC (Associazione Italiana Ricerca sul Cancro) [IG 15364]; Rosemere Cancer Foundation; New Jersey Health Foundation; Fondo Nacional de Ciencia y Tecnologia (FONDECYT), Ministerio de Educacion de Chile (MINEDUC), Universidad de Tarapao (UTA); Flemish Institute for Technological Research (VITO), Belgium; National Centre for the Replacement, Refinement and Reduction (NC3Rs) of animals in research [NC.K500045.1, G0800697]; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Japan Science and Technology Agency; JST, CREST; Ministry of Science and Technology of Taiwan [NSC93-2314-B-320-006, NSC94-2314-B-320-002]; National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology [2012R1A2A2A01010870]; Ministry of Health and Welfare, Republic of Korea [HI13C1449]; UAMS/NIH Clinical and Translational Science Award [UL1TR000039, KL2TR000063]; Arkansas Biosciences Institute; Czech Science Foundation [13-07711S]; NIH [CA116812]; National Institute of Environmental Health Sciences [ES016893]; Maine Center for Toxicology and Environmental Health; FERO Foundation in Barcelona, Spain; Cancer Research UK; International Journal of Experimental Pathology; Swim Across America Cancer Research Award; American Cancer Society [116683-RSG-09-087-01-TBE]; Fund for Scientific Research-Flanders (FWO-Vlaanderen); Inter University Attraction Pole grant [IAP-P7-07]; Miguel Servet Research Contract Program [CP10/00656]; Taipei Medical University [TMU101-AE3-Y19]; Genesis Oncology Trust (NZ) Professional Development Grant; Faculty of Medicine, University of Otago, Dunedin, New Zealand; Dutch Cancer Society [UVA2011-4969]; AICR [14-1164]; Breast Cancer Research Program [W81XWH-14-1-0087]; Department of Science and Technology, Government of India [SR/FT/LS-063/2008]; NIEHS contracts [N01-ES 35504, HHSN27320140003C]; King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia [T.K. 11-0629]; Dalhousie Medical Research Foundation; Beatrice Hunter Cancer Institute; CIHR; Nova Scotia Lung Association; PHS grants from the NIH [R01-CA141704, R01-CA150214, R01-DK52825, R01-CA61774]; Charles University in Prague [UNCE 204015, PRVOUK P31/2012]; Health and Medical Research Fund of Food and Health Bureau, Hong Kong Special Administrative Region [10110021]; [PI12/01104]; [CP03/00101] FX We gratefully acknowledge the support of the National Institute of Health-National Institute of Environmental Health Sciences (NIEHS) conference grant travel support (R13ES023276); Glenn Rice, Office of Research and Development, United States Environmental Protection Agency, Cincinnati, OH, USA also deserves thanks for his thoughtful feedback and inputs on the manuscript; William H.Goodson III was supported by the California Breast Cancer Research Program, Clarence Heller Foundation and California Pacific Medical Center Foundation; Abdul M.Ali would like to acknowledge the financial support of the University of Sultan Zainal Abidin, Malaysia; Ahmed Lasfar was supported by an award from the Rutgers Cancer Institute of New Jersey; Ann-Karin Olsen and Gunnar Brunborg were supported by the Research Council of Norway (RCN) through its Centres of Excellence funding scheme (223268/F50), Amancio Camaro's lab was supported by grants from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0306-2012); Matilde E. Lleonart was supported by a trienal project grant PI12/01104 and by project CP03/00101 for personal support. Amaya Azqueta would like to thank the Ministerio de Educacion y Ciencia (Juande la Cierva' programme, 2009) of the Spanish Government for personal support; Amedeo Amedei was supported by the Italian Ministry of University and Research (2009FZZ4XM_002), and the University of Florence (ex60%2012); Andrew R.Collins was supported by the University of Oslo; Annamaria Colacci was supported by the Emilia-Romagna Region - Project 'Supersite' in Italy; Carolyn Baglole was supported by a salary award from the Fonds de recherche du Quebec-Sante (FRQ-S); Chiara Mondello's laboratory is supported by Fondazione Cariplo in Milan, Italy (grant n. 2011-0370); Christian C.Naus holds a Canada Research Chair; Clement Yedjou was supported by a grant from the National Institutes of Health (NIH-NIMHD grant no. G12MD007581); Daniel C.Koch is supported by the Burroughs Wellcome Fund Postdoctoral Enrichment Award and the Timor Biology Training grant: NIH T32CA09151; Dean W. Felsher would like to acknowledge the support of United States Department of Health and Human Services, NIH grants (R01 CA170378 PQ22, RO1 CA184384, U54 CA149145, U54 CA151459, P50 CA114747 and 1121 CA169964); Emilio Rojas would like to thank CONACyT support 152473; Ezio Laconi was supported by AIRC (Italian Association for Cancer Research, grant no. IG 14640) and by the Sardinian Regional Government (RAS); Eun-Yi Moon was supported by grants from the Public Problem-Solving Program (NRF-015M3C8A6A06014500) and Nuclear R&D Program (#2013M2B2A9A03051296 and 2010-0018545) through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science and Technology (MEST) in Korea; Fahd Al-Mulla was supported by the Kuwait Foundation for the Advancement of Sciences (2011-1302-06); Ferdinando Chiaradonna is supported by SysBioNet, a grant for the Italian Roadmap of European Strategy Forum on Research Infrastructures (ESFRI) and by AIRC (Associazione Italiana Ricerca sul Cancro; IG 15364); Francis L.Martin acknowledges funding from Rosemere Cancer Foundation; he also thanks Lancashire Teaching Hospitals NHS trust and the patients who have facilitated the studies he has undertaken over the course of the last 10 years; Gary S.; Goldberg would like to acknowledge the support of the New Jersey Health Foundation; Gloria M.Calaf was supported by Fondo Nacional de Ciencia y Tecnologia (FONDECYT), Ministerio de Educacion de Chile (MINEDUC), Universidad de Tarapac6 (UTA); Gudrun Koppen was supported by the Flemish Institute for Technological Research (VITO), Belgium; Hemad Yasaei was supported from a triennial project grant (Strategic Award) from the National Centre for the Replacement, Refinement and Reduction (NC3Rs) of animals in research (NC.K500045.1 and G0800697); Hiroshi Kondoh was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Science and Technology Agency and by JST, CREST; Hsue-Yin Hsu was supported by the Ministry of Science and Technology of Taiwan (NSC93-2314-B-320-006 and NSC94-2314-B-320-002); Hyun Ho Park was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology (2012R1A2A2A01010870) and a grant from the Korea Healthcare Technology R&D project, Ministry of Health and Welfare, Republic of Korea (HI13C1449); Igor Koturbash is supported by the UAMS/NIH Clinical and Translational Science Award (UL1TR000039 and KL2TR000063) and the Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000; Jan VondrLek acknowledges funding from the Czech Science Foundation (13-07711S); Jesse Roman thanks the NIH for their support (CA116812); John Pierce Wise Sr. and Sandra S.Wise were supported by National Institute of Environmental Health Sciences (ES016893 to J.P.W.) and the Maine Center for Toxicology and Environmental Health; Jonathan Whitfield acknowledges support from the FERO Foundation in Barcelona, Spain; Joseph Christopher is funded by Cancer Research UK and the International Journal of Experimental Pathology; Julia Kravchenko is supported by a philanthropic donation by Fred and Alice Stanback; Jun Sun is supported by a Swim Across America Cancer Research Award; Karine A.Cohen-Solal is supported by a research scholar grant from the American Cancer Society (116683-RSG-09-087-01-TBE); Laetitia Gonzalez received a postdoctoral fellowship from the Fund for Scientific Research-Flanders (FWO-Vlaanderen) and support by an Inter University Attraction Pole grant (IAP-P7-07); Laura Soucek is supported by grant #CP10/00656 from the Miguel Servet Research Contract Program and acknowledges support from the FERO Foundation in Barcelona, Spain; Liang-Tzung Lin was supported by funding from the Taipei Medical University (TMU101-AE3-Y19); Linda Gulliver is supported by a Genesis Oncology Trust (NZ) Professional Development Grant, and the Faculty of Medicine, University of Otago, Dunedin, New Zealand; Louis Vermeulen is supported by a Fellowship of the Dutch Cancer Society (KWF, UVA2011-4969) and a grant from the AICR (14-1164); Mahara Valverde would like to thank CONACyT support 153781; Masoud H. Manjili was supported by the office of the Assistant Secretary of Defense for Health Affairs (USA) through the Breast Cancer Research Program under Award No. W81XWH-14-1-0087 Neetu Singh was supported by grant #SR/FT/LS-063/2008 from the Department of Science and Technology, Government of India; Nicole Kleinstreuer is supported by NIEHS contracts (N01-ES 35504 and HHSN27320140003C); P.K. Krishnakumar is supported by the Funding (No. T.K. 11-0629) of King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia; Paola A.; Marignani is supported by the Dalhousie Medical Research Foundation, The Beatrice Hunter Cancer Institute and CIHR and the Nova Scotia Lung Association; Paul Dent is the holder of the Universal Inc. Chair in Signal Transduction Research and is supported with funds from PHS grants from the NIH (R01-CA141704, R01-CA150214, R01-DK52825 and R01-CA61774); Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, and by the Czech Science Foundation projects P301/12/1686 and 15-03834Y; Po Sing Leung was supported by the Health and Medical Research Fund of Food and Health Bureau, Hong Kong Special Administrative Region, Ref. No: 10110021; Qiang Cheng was supported in part by grant NSF IIS4218712; R. Brooks Robey is supported by the United States Department of Veterans Affairs; Rabindra Roy was supported by United States Public Health Service Grants (RO1 CA92306, RO1 CA92306-S1 and RO1 CA113447); Rafaela AndradeVieira is supported by the Beatrice Hunter Cancer Research Institute and the Nova Scotia Health Research Foundation; Renza Vento was partially funded by European Regional Development Fund, European Territorial Cooperation 2007-13 (CCI 2007 CB 163 PO 037, OP Italia-Malta 2007-13) and grants from the Italian Ministry of Education, University and Research (MIUR) ex-60%, 2007; Riccardo Di Fiore was a recipient of fellowship granted by European Regional Development Fund, European Territorial Cooperation 2007-2013 (CCI 2007 CB 163 PO 037, OP Italia-Malta 2007-2013); Rita Dornetshuber-Fleiss was supported by the Austrian Science Fund (FWF, project number T 451-B18) and the Johanna Mahlke, geb.-Obermann-Stiftung; Roberta Palorini is supported by a SysBioNet fellowship; Roslida Abd Hamid is supported by the Ministry of Education, Malaysia-Exploratory Research Grant Scheme-Project no: ERGS/1-2013/5527165; Sabine A.S.Langie is the beneficiary of a postdoctoral grant from the AXA Research Fund and the Cefic-LRI Innovative Science Award 2013; Sakina Eltom is supported by NIH grant SC1CA153326; Samira A. Brooks was supported by National Research Service Award (T32 ES007126) from the National Institute of Environmental Health Sciences and the HHMI Translational Medicine Fellowship; Sandra Ryeom was supported by The Garrett B. Smith Foundation and the TedDriven Foundation; Thierry Massfelder was supported by the Institut National de la Sante et de la Recherche Medicale INSERM and Universite de Strasbourg; Thomas Sanderson is supported by the Canadian Institutes of Health Research (CIHR; MOP115019), the Natural Sciences and Engineering Council of Canada (NSERC; 313313) and the California Breast Cancer Research Program (CBCRP; 17UB-8703); Tiziana Guarnieri is supported by a grant from Fundamental Oriented Research (RFO) to the Alma Mater Studiorum University of Bologna, Bologna, Italy and thanks the Fondazione Cassa di Risparmio di Bologna and the Fondazione Banca del Monte di Bologna e Ravenna for supporting the Center for Applied Biomedical Research, S.Orsola-Malpighi University Hospital, Bologna, Italy; W.Kimryn Rathmell is supported by the V Foundation for Cancer Research and the American Cancer Society; William K.Decker was supported in part by grant RP110545 from the Cancer Prevention Research Institute of Texas; William H.; Bisson was supported with funding from the NIH P30 ES000210; Yon Rojanasakul was supported with NIH grant R01-ES022968; Zhenbang Chen is supported by NIH grants (MD004038, CA163069 and MD007593); Zhiwei Hu is grateful for the grant support from an institutional start-up fund from The Ohio State University College of Medicine and The OSU James Comprehensive Cancer Center (OSUCCC) and a Seed Award from the OSUCCC Translational Therapeutics Program, NR 508 TC 34 Z9 36 U1 16 U2 76 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2015 VL 36 SU 1 BP S254 EP S296 DI 10.1093/carcin/bgv039 PG 43 WC Oncology SC Oncology GA CL6AQ UT WOS:000357048100013 PM 26106142 ER PT J AU Hu, ZW Brooks, SA Dormoy, V Hsu, CW Hsu, HY Lin, LT Massfelder, T Rathmell, WK Xia, MH Al-Mulla, F Al-Temaimi, R Amedei, A Brown, DG Prudhomme, KR Colacci, A Hamid, RA Mondello, C Raju, J Ryan, EP Woodrick, J Scovassi, AI Singh, N Vaccari, M Roy, R Forte, S Memeo, L Salem, HK Lowe, L Jensen, L Bisson, WH Kleinstreuer, N AF Hu, Zhiwei Brooks, Samira A. Dormoy, Valerian Hsu, Chia-Wen Hsu, Hsue-Yin Lin, Liang-Tzung Massfelder, Thierry Rathmell, W. Kimryn Xia, Menghang Al-Mulla, Fahd Al-Temaimi, Rabeah Amedei, Amedeo Brown, Dustin G. Prudhomme, Kalan R. Colacci, Annamaria Hamid, Roslida A. Mondello, Chiara Raju, Jayadev Ryan, Elizabeth P. Woodrick, Jordan Scovassi, A. Ivana Singh, Neetu Vaccari, Monica Roy, Rabindra Forte, Stefano Memeo, Lorenzo Salem, Hosni K. Lowe, Leroy Jensen, Lasse Bisson, William H. Kleinstreuer, Nicole TI Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis SO CARCINOGENESIS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; ARYL-HYDROCARBON RECEPTOR; NF-KAPPA-B; INTERCELLULAR-ADHESION MOLECULE-1; IN-VITRO MODELS; HUMAN-TISSUE FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION; UROKINASE PLASMINOGEN-ACTIVATOR; PERFLUOROOCTANE SULFONATE PFOS; THROUGHPUT SCREENING PLATFORM AB Angiogenesis is an important 'hallmark' of cancer. We reviewed the various pathways controlling angiogenesis, summarized the possible role of specific environmental chemicals disrupting these pathways and listed assays for assessing the effects of low-dose exposures to chemicals in promoting tumor angiogenesis.One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential. C1 [Hu, Zhiwei] Ohio State Univ, Coll Med, Dept Surg, Columbus, OH 43210 USA. [Hu, Zhiwei] Ohio State Univ, Coll Med, James Comprehens Canc Ctr, Columbus, OH 43210 USA. [Brooks, Samira A.; Rathmell, W. Kimryn] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Dormoy, Valerian; Massfelder, Thierry] Univ Strasbourg, Fac Med, INSERM, U1113,Team Cell Signalling & Commun Kidney & Pros, F-67085 Strasbourg, France. [Dormoy, Valerian] Univ Calif Irvine, Dept Cell & Dev Biol, Irvine, CA 92697 USA. [Hsu, Chia-Wen; Xia, Menghang] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Hsu, Hsue-Yin; Al-Mulla, Fahd] Tzu Chi Univ, Dept Life Sci, Hualien, Taiwan. [Lin, Liang-Tzung] Taipei Med Univ, Dept Microbiol & Immunol, Taipei, Taiwan. [Al-Temaimi, Rabeah] Kuwait Univ, Dept Pathol, Safat 13110, Kuwait. [Amedei, Amedeo] Univ Firenze, Dept Expt & Clin Med, I-50134 Florence, Italy. [Brown, Dustin G.; Ryan, Elizabeth P.] Colorado State Univ, Colorado Sch Publ Hlth, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. [Prudhomme, Kalan R.; Bisson, William H.] Oregon State Univ, Environm Hlth Sci Ctr, Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Colacci, Annamaria; Vaccari, Monica] Environm Protect & Hlth Prevent Agcy, Ctr Environm Carcinogenesis & Risk Assessment, Bologna, Italy. [Hamid, Roslida A.] Univ Putra Malaysia, Fac Med & Hlth Sci, Serdang 43400, Selangor, Malaysia. [Mondello, Chiara; Scovassi, A. Ivana] CNR, Inst Mol Genet, I-27100 Pavia, Italy. [Raju, Jayadev] Hlth Canada, Regulatory Toxicol Res Div, Bur Chem Safety, Food Directorate,Hlth Prod & Food Branch, Ottawa, ON K1A0K9, Canada. [Woodrick, Jordan; Roy, Rabindra] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Singh, Neetu] King Georges Med Univ, Adv Mol Sci Res Ctr, Ctr Adv Res, Lucknow 226003, Uttar Pradesh, India. [Forte, Stefano; Memeo, Lorenzo] Mediterranean Inst Oncol, I-95029 Viagjande, Italy. [Salem, Hosni K.] Cairo Univ, Kasr Al Ainy Sch Med, Dept Urol, Cairo 12515, Egypt. [Lowe, Leroy] Getting Know Canc, Truro, NS B2N 1X5, Canada. [Jensen, Lasse] Linkoping Univ, Dept Med & Hlth Sci, Div Cardiovasc Med, Linkoping, Sweden. [Kleinstreuer, Nicole] Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. RP Hu, ZW (reprint author), Ohio State Univ, Coll Med, Dept Surg, Columbus, OH 43210 USA. EM zhiwei.hu@osumc.edu RI Hu, Zhiwei/L-3727-2013; Massfelder, Thierry/I-1260-2016; Dormoy, Valerian/P-5109-2016; Forte, Stefano/D-3645-2013; Mondello, Chiara/B-8305-2015; OI Hu, Zhiwei/0000-0002-0023-1170; Forte, Stefano/0000-0001-5746-7451; Mondello, Chiara/0000-0002-8379-9246; Scovassi, Anna Ivana/0000-0003-3484-9881; Kleinstreuer, Nicole/0000-0002-7914-3682 FU Ohio State University College of Medicine; The OSU James Comprehensive Cancer Center (OSUCCC); OSUCCC Translational Therapeutics Program; Ministry of Science and Technology of Taiwan [NSC93-2314-B-320-006, NSC94-2314-B-320-002]; Taipei Medical University [TMU101-AE3-Y19]; INSERM; University of Strasbourg, France; Fondazione Cariplo [2011-0370]; Kuwait Institute for the Advancement of Sciences [2011-1302-06]; Grant University Scheme (RUGS) Ministry Of Education Malaysia [04-02-12-2099RU]; Italian Ministry of University and Research [2009FZZ4XM_002]; University of Florence; US Public Health Service [RO1 CA92306, RO1 CA92306-51, RO1 CA113447]; Department of Science and Technology, Government of India [SR/FT/LS-063/2008]; NIEHS [N01-ES 35504, HHSN27320140003C] FX The Ohio State University College of Medicine, The OSU James Comprehensive Cancer Center (OSUCCC), OSUCCC Translational Therapeutics Program (to Z. H.); Ministry of Science and Technology of Taiwan (NSC93-2314-B-320-006 and NSC94-2314-B-320-002 to H.-Y. H.); Taipei Medical University (TMU101-AE3-Y19 to L.-T. L); INSERM and University of Strasbourg, France (to T. M.); Fondazione Cariplo (2011-0370 to CM.); Kuwait Institute for the Advancement of Sciences (2011-1302-06 to F. al-M.); Grant University Scheme (RUGS) Ministry Of Education Malaysia (04-02-12-2099RU to R.A.H.); Italian Ministry of University and Research (2009FZZ4XM_002 to A.A); the University of Florence (ex60%2012 to A.A.); US Public Health Service Grants (RO1 CA92306, RO1 CA92306-51, RO1 CA113447 to R.R.); Department of Science and Technology, Government of India (SR/FT/LS-063/2008 to N.S.); NIEHS contracts (N01-ES 35504 and HHSN27320140003C to N.K.). NR 365 TC 6 Z9 6 U1 8 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2015 VL 36 SU 1 BP S184 EP S202 DI 10.1093/carcin/bgv036 PG 19 WC Oncology SC Oncology GA CL6AQ UT WOS:000357048100010 PM 26106137 ER PT J AU Thompson, PA Khatami, M Baglole, CJ Sun, J Harris, S Moon, EY Al-Mulla, F Al-Temaimi, R Brown, D Colacci, A Mondello, C Raju, J Ryan, E Woodrick, J Scovassi, I Singh, N Vaccari, M Roy, R Forte, S Memeo, L Salem, HK Amedei, A Hamid, RA Lowe, L Guarnieri, T Bisson, WH AF Thompson, Patricia A. Khatami, Mahin Baglole, Carolyn J. Sun, Jun Harris, Shelley Moon, Eun-Yi Al-Mulla, Fahd Al-Temaimi, Rabeah Brown, Dustin Colacci, Annamaria Mondello, Chiara Raju, Jayadev Ryan, Elizabeth Woodrick, Jordan Scovassi, Ivana Singh, Neetu Vaccari, Monica Roy, Rabindra Forte, Stefano Memeo, Lorenzo Salem, Hosni K. Amedei, Amedeo Hamid, Roslida A. Lowe, Leroy Guarnieri, Tiziana Bisson, William H. TI Environmental immune disruptors, inflammation and cancer risk SO CARCINOGENESIS LA English DT Review ID NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; POLYBROMINATED DIPHENYL ETHERS; ESTROGEN-RECEPTOR-ALPHA; NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITION; PROLIFERATOR-ACTIVATED RECEPTOR; MIGRATION INHIBITORY FACTOR; DIESEL EXHAUST PARTICLES; ARYL-HYDROCARBON RECEPTOR AB Exposure to common environmental chemicals at low doses and in mixtures that act as immune disruptors and destabilize the balance of pro- and anti-inflammatory responses in favor of inflammation may increase cancer risk in exposed individuals. This risk and the potential for transgenerational inheritance through epigenetic effects to offspring are understudied in the cancer field and overlooked by current toxicant screening platforms for carcinogenesis.An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular targets involved in tumor-associated inflammation (e.g. cyclooxygenase/prostaglandin E-2, nuclear factor kappa B, nitric oxide synthesis, cytokines and chemokines) are presented as example chemically mediated target molecule perturbations relevant to cancer. Commentary on areas of additional research including the need for innovation and integration of systems biology approaches to the study of environmental exposures and cancer causation are presented. C1 [Thompson, Patricia A.] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA. [Khatami, Mahin] NCI, Inflammat & Canc Res, NIH, Bethesda, MD 20817 USA. [Baglole, Carolyn J.] McGill Univ, Dept Med, Montreal, PQ H2X 2P2, Canada. [Sun, Jun] Rush Univ, Dept Biochem, Chicago, IL 60612 USA. [Harris, Shelley] Canc Care Ontario, Prevent & Canc Control, Toronto, ON M5G 2L3, Canada. [Moon, Eun-Yi] Sejong Univ, Dept Biosci & Biotechnol, Seoul 143747, South Korea. [Al-Mulla, Fahd; Al-Temaimi, Rabeah] Kuwait Univ, Dept Pathol, Safat 13110, Kuwait. [Brown, Dustin; Ryan, Elizabeth] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Colorado Sch Publ Hlth, Ft Collins, CO 80523 USA. [Colacci, Annamaria; Vaccari, Monica] Environm Protect & Hlth Prevent Agcy, Ctr Environm Carcinogenesis & Risk Assessment, I-40126 Bologna, Italy. [Mondello, Chiara; Scovassi, Ivana] CNR, Inst Mol Genet, I-27100 Pavia, Italy. [Raju, Jayadev] Hlth Prod & Food Branch Hlth Canada, Bur Chem Safety Food Directorate, Toxicol Res Div, Ottawa, ON K1A 0K9, Canada. [Woodrick, Jordan; Roy, Rabindra] Georgetown Univ, Med Ctr, Mol Oncol Program, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Singh, Neetu] King Georges Med Univ, Adv Mol Sci Res Ctr, Lucknow 226003, Uttar Pradesh, India. [Forte, Stefano; Memeo, Lorenzo] Mediterranean Inst Oncol, I-95029 Viagrande, Italy. [Salem, Hosni K.] Cairo Univ, Dept Urol, Kasr Al Ainy Sch Med, Cairo 12515, Egypt. [Amedei, Amedeo] Univ Florence, Dept Expt & Clin Med, I-50134 Florence, Italy. [Hamid, Roslida A.] Univ Putra Malaysia, Fac Med & Hlth Sci, Serdang 43400, Malaysia. [Lowe, Leroy] Getting Know Canc, Truro, NS B2N 1X5, Canada. [Guarnieri, Tiziana] Alma Mater Studiorum Univ Bologna, Dept Biol Geol & Environm Sci, I-40126 Bologna, Italy. [Guarnieri, Tiziana] S Orsola Malpighi Univ Hosp, Ctr Appl Biomed Res, I-40126 Bologna, Italy. [Guarnieri, Tiziana] Natl Inst Biostruct & Biosyst, I-00136 Rome, Italy. [Bisson, William H.] Oregon State Univ, Environm Hlth Sci Ctr, Environm & Mol Toxicol, Corvallis, OR 97331 USA. RP Thompson, PA (reprint author), SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA. EM patricia.thompson-carino@stonybrookmedicine.edu; bissonw@science.oregonstate.edu RI Forte, Stefano/D-3645-2013 OI Scovassi, Anna Ivana/0000-0003-3484-9881; Forte, Stefano/0000-0001-5746-7451 FU National Institute of Environmental Health Sciences [P30 E5000210] FX National Institute of Environmental Health Sciences (P30 E5000210 to W.H.B.). NR 277 TC 20 Z9 20 U1 9 U2 40 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2015 VL 36 SU 1 BP S232 EP S253 DI 10.1093/carcin/bgv038 PG 22 WC Oncology SC Oncology GA CL6AQ UT WOS:000357048100012 PM 26106141 ER PT J AU Lodish, MB Yuan, B Levy, I Braunstein, GD Lyssikatos, C Salpea, P Szarek, E Karageorgiadis, AS Belyavskaya, E Raygada, M Faucz, FR Izatt, L Brain, C Gardner, J Quezado, M Carney, JA Lupski, JR Stratakis, CA AF Lodish, Maya B. Yuan, Bo Levy, Isaac Braunstein, Glenn D. Lyssikatos, Charalampos Salpea, Paraskevi Szarek, Eva Karageorgiadis, Alexander S. Belyavskaya, Elena Raygada, Margarita Faucz, Fabio Rueda Izatt, Louise Brain, Caroline Gardner, James Quezado, Martha Carney, J. Aidan Lupski, James R. Stratakis, Constantine A. TI Germline PRKACA amplification causes variable phenotypes that may depend on the extent of the genomic defect: molecular mechanisms and clinical presentations SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-A; ADRENAL CUSHINGS-SYNDROME; CATALYTIC SUBUNIT; SOMATIC MUTATIONS; TUMORS; REARRANGEMENTS; ADENOMAS; CORTISOL; COMPLEX; PKA AB Objective: We have recently reported five patients with bilateral adrenocortical hyperplasia (BAH) and Cushing's syndrome (CS) caused by constitutive activation of the catalytic subunit of protein kinase A (PRKACA). By doing new in-depth analysis of their cytogenetic abnormality, we attempted a better genotype-phenotype correlation of their PRKACA amplification. Design: This study is a case series. Methods: Molecular cytogenetic, genomic, clinical, and histopathological analyses were performed in five patients with CS. Results: Reinvestigation of the defects of previously described patients by state-of-the-art molecular cytogenetics showed complex genomic rearrangements in the chromosome 19p13.2p13.12 locus, resulting in copy number gains encompassing the entire PRKACA gene; three patients (one sporadic case and two related cases) were observed with gains consistent with duplications, while two sporadic patients were observed with gains consistent with triplications. Although all five patients presented with ACTH-independent CS, the three sporadic patients had micronodular BAH and underwent bilateral adrenalectomy in early childhood, whereas the two related patients, a mother and a son, presented with macronodular BAH as adults. In at least one patient, PRKACA triplication was associated with a more severe phenotype. Conclusions: Constitutional chromosomal PRKACA gene amplification is a recently identified genetic defect associated with CS, a trait that may be inherited in an autosomal dominant manner or occur de novo. Genomic rearrangements can be complex and can result in different copy number states of dosage-sensitive genes, e.g., duplication and triplication. PRKACA amplification can lead to variable phenotypes clinically and pathologically, both micro- and macro-nodular BAH, the latter of which we speculate may depend on the extent of amplification. C1 [Lodish, Maya B.; Levy, Isaac; Lyssikatos, Charalampos; Salpea, Paraskevi; Szarek, Eva; Karageorgiadis, Alexander S.; Belyavskaya, Elena; Raygada, Margarita; Faucz, Fabio Rueda; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Yuan, Bo; Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Braunstein, Glenn D.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Izatt, Louise] Guys Hosp, Dept Clin Genet, London SE1 9RT, England. [Brain, Caroline] Great Ormond St Hosp Sick Children, Dept Endocrinol, London WC1N 3JH, England. [Gardner, James] Our Lady Lake Childrens Hosp, Dept Pediat, Baton Rouge, LA USA. [Quezado, Martha] NCI, Dept Pathol, Bethesda, MD 20892 USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Lodish, MB (reprint author), NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10 CRC,Room 9D42,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov FU Intramural division of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; [NINDS RO1NS058529]; [NHGRI U54HG006542] FX This research was supported by the Intramural division of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institutes of Health and extramural grants NINDS RO1NS058529 and NHGRI U54HG006542. Clinical trial registration number: NCT00001452. NR 30 TC 5 Z9 6 U1 0 U2 4 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JUN PY 2015 VL 172 IS 6 BP 803 EP 811 DI 10.1530/EJE-14-1154 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CL8GR UT WOS:000357212600024 PM 25924874 ER PT J AU Douketis, J Spyropoulos, A Kaatz, S Caprini, J Dunn, A Garcia, D Jacobson, A Jaffer, A Kindzelski, A Schulman, S Turpie, AG Becker, R Clark, NP Conti, B Ellsworth, S Harrison, RW Kong, D Johnson, G Krishnamoorthy, A Palmeri, S Parker, W Saucedo, J Schoch, P Tallman, D Witt, D Hasselblad, V Ortel, TL AF Douketis, J. Spyropoulos, A. Kaatz, S. Caprini, J. Dunn, A. Garcia, D. Jacobson, A. Jaffer, A. Kindzelski, A. Schulman, S. Turpie, A. G. Becker, R. Clark, N. P. Conti, B. Ellsworth, S. Harrison, R. W. Kong, D. Johnson, G. Krishnamoorthy, A. Palmeri, S. Parker, W. Saucedo, J. Schoch, P. Tallman, D. Witt, D. Hasselblad, V Ortel, T. L. CA BRIDGE Study Investigators TI Bridging anticoagulation in patients who require temporary interruption of warfarin therapy for an elective invasive procedure or surgery (the bridge trial) SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Douketis, J.] St Josephs Healthcare, Hamilton, ON, Canada. [Douketis, J.; Turpie, A. G.] McMaster Univ, Hamilton, ON, Canada. [Spyropoulos, A.; Ortel, T. L.] Lenox Hill Hosp, North Shore LIJ Hlth Syst, Hofstra North Shore LIJ Sch Med, New York, NY 10021 USA. [Kaatz, S.; Ortel, T. L.] Hurley Med Ctr, Flint, MI USA. [Caprini, J.] North Shore Univ Hlth Syst, New York, NY USA. [Dunn, A.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Garcia, D.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Jacobson, A.] VA Loma Linda Healthcare Syst, Loma Linda, CA USA. [Jaffer, A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Kindzelski, A.] NHLBI, Bethesda, MD 20892 USA. [Schulman, S.] Hamilton Hlth Sci Ctr, Hamilton, ON, Canada. [Becker, R.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Clark, N. P.] Kaiser Permanente Colorado, Lafayette, CO USA. [Conti, B.] Owen Sound Family Hlth Team, Owen Sound, ON, Canada. [Ellsworth, S.] Henry Ford Hosp, Detroit, MI 48202 USA. [Harrison, R. W.; Kong, D.; Krishnamoorthy, A.; Parker, W.; Hasselblad, V] Duke Univ, Durham, NC USA. [Johnson, G.] Univ Minnesota, Minneapolis, MN USA. [Palmeri, S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Saucedo, J.] NorthShore Univ HealthSyst, New York, NY USA. [Schoch, P.] US Dept Vet Affairs, Washington, DC USA. [Witt, D.] Univ Utah, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 7 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 2015 VL 13 SU 2 SI SI MA LB002 BP 83 EP 84 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CK7QJ UT WOS:000356426901228 ER PT J AU Novack, A St-Louis, J Greist, A Shapiro, A Smith, H Chowdary, P Drebes, A Lozier, J Bourgeois, C Mo, M Farin, H AF Novack, A. St-Louis, J. Greist, A. Shapiro, A. Smith, H. Chowdary, P. Drebes, A. Lozier, J. Bourgeois, C. Mo, M. Farin, H. TI Perioperative management of bleeds with recombinant porcine FVIII in patients with acquired hemophilia A SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Novack, A.; Mo, M.; Farin, H.] Baxter Healthcare Corp, BioSci, Westlake Village, CA USA. [St-Louis, J.] Univ Montreal, Hop Maisonneuve Rosemont, Div Hematol, Montreal, PQ, Canada. [Greist, A.; Shapiro, A.] Hemophilia & Thrombosis Ctr, Indianapolis, IN USA. [Smith, H.] Tufts Univ New England Med Ctr, Div Hematol Oncol, Boston, MA USA. [Chowdary, P.; Drebes, A.] Royal Free Hosp, Katharine Dormandy Haemophilia Ctr, London NW3 2QG, England. [Chowdary, P.; Drebes, A.] Royal Free Hosp, Thrombosis Unit, London NW3 2QG, England. [Lozier, J.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Bourgeois, C.] Baxter Innovat, BioSci, Vienna, Austria. NR 0 TC 1 Z9 1 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 2015 VL 13 SU 2 SI SI MA OR028 BP 104 EP 104 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CK7QJ UT WOS:000356426901278 ER PT J AU Mansfield, A Tafur, AJ Vulih, D Smith, GL Harris, PJ Ivy, SP AF Mansfield, A. Tafur, A. J. Vulih, D. Smith, G. L. Harris, P. J. Ivy, Percy S. TI Differences in venous thromboembolic events in subjects enrolled in standard phase I clinical trials and those on phase I hepatic dysfunction clinical trials SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Mansfield, A.] Mayo Clin, Med Oncol, Rochester, MN USA. [Tafur, A. J.] OUHSC, Vasc Med, Oklahoma City, OK USA. [Vulih, D.] Theradex, Princeton, NJ USA. [Smith, G. L.] NCI, Clin Trials Monitoring Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Harris, P. J.; Ivy, Percy S.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 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 2015 VL 13 SU 2 SI SI MA OR127 BP 142 EP 142 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CK7QJ UT WOS:000356426901377 ER PT J AU Iyer, J Slovak, M Francischetti, I Ribeiro, J Kini, M AF Iyer, J. Slovak, M. Francischetti, I Ribeiro, J. Kini, M. TI Quantitative transcriptome and proteome analysis of dermacentor reticulatus salivary glands for the identification of novel anticoagulants and immunomodulatory proteins SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Iyer, J.; Kini, M.] Natl Univ Singapore, Dept Biol Sci, Singapore 117548, Singapore. [Slovak, M.] Slovak Acad Sci, Inst Zool, Bratislava, Slovakia. [Francischetti, I; Ribeiro, J.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Kini, M.] Univ S Australia, Sch Pharm & Med Sci, Adelaide, SA 5001, Australia. [Kini, M.] Univ Oxford, Dept Zool, Oxford, England. [Kini, M.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Biochem & Mol Biol, Richmond, VA 23298 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 2015 VL 13 SU 2 SI SI MA PO341-TUE BP 631 EP 631 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CK7QJ UT WOS:000356426904058 ER PT J AU Sayed, IM Verhoye, L Debing, Y Abbravanel, F Farhoudi, A Leroux-Roels, G Neyts, J Izopet, J Purcell, R Emerson, S Meuleman, P AF Sayed, I. M. Verhoye, L. Debing, Y. Abbravanel, F. Farhoudi, A. Leroux-Roels, G. Neyts, J. Izopet, J. Purcell, R. Emerson, S. Meuleman, P. TI Human liver chimeric mice as a novel model for the study of hepatitis E virus infections SO JOURNAL OF VIRAL HEPATITIS LA English DT Meeting Abstract CT 15th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD) CY JUN 26-28, 2015 CL Berlin, GERMANY C1 [Sayed, I. M.; Verhoye, L.; Farhoudi, A.; Leroux-Roels, G.; Meuleman, P.] Univ Ghent, Ctr Vaccinol, B-9000 Ghent, Belgium. [Debing, Y.; Neyts, J.] Katholieke Univ Leuven, Rega Inst, Leuven, Belgium. [Abbravanel, F.; Izopet, J.] CHU Purpan, INSERM U1043, IFR BMT, Toulouse, France. [Abbravanel, F.; Izopet, J.] Univ Toulouse 3, Virol Lab, CHU Purpan, F-31062 Toulouse, France. [Purcell, R.; Emerson, S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 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 1352-0504 EI 1365-2893 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JUN PY 2015 VL 22 SU 2 SI SI MA O-22 BP 13 EP 13 DI 10.1111/jvh.20_12424 PG 1 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA CL3XB UT WOS:000356884200022 ER PT J AU Ouaguia, L Morales, O Wychowski, C Carpentier, A Aoudjehane, L Dubuisson, J Calmus, Y de Launoit, Y Conti, F Delhem, N AF Ouaguia, L. Morales, O. Wychowski, C. Carpentier, A. Aoudjehane, L. Dubuisson, J. Calmus, Y. de launoit, Y. Conti, F. Delhem, N. TI The hepatitis C virus contributes to the aggravation of the immunosuppressive environment by increasing the suppressive activity of natural regulatory T cells and inducing the emergence of type 1 regulatory T Cells SO JOURNAL OF VIRAL HEPATITIS LA English DT Meeting Abstract CT 15th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD) CY JUN 26-28, 2015 CL Berlin, GERMANY C1 [Ouaguia, L.; Morales, O.; de launoit, Y.; Delhem, N.] Inst Pasteur, Ctr Immunol & Biol Parasitaire, CNRS, Biol Inst Lille,UMR8161, F-59019 Lille, France. [Wychowski, C.; Dubuisson, J.] Inst Pasteur, Ctr Immunol & Biol Parasitaire, CNRS, Ctr Infect & Immunite Lille,INSERM,UMR8204,U1019, F-59019 Lille, France. [Carpentier, A.] NIH, Bethesda, MD 20892 USA. [Aoudjehane, L.; Calmus, Y.; Conti, F.] Univ Paris 06, Paris, France. [Aoudjehane, L.] INSERM, UMR S 938, Paris, France. [Calmus, Y.; Conti, F.] INSERM, UMR S 938, CdR St Antoine, Paris, France. [Calmus, Y.; Conti, F.] Univ Paris 05, Fac Med Rene Descartes, Paris, France. 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 1352-0504 EI 1365-2893 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JUN PY 2015 VL 22 SU 2 SI SI MA P153 BP 96 EP 96 DI 10.1111/jvh.141_12425 PG 1 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA CL3XB UT WOS:000356884200173 ER PT J AU Adoro, S Cubillos-Ruiz, JR Chen, X Deruaz, M Vrbanac, VD Song, M Park, S Murooka, TT Dudek, TE Luster, AD Tager, AM Streeck, H Bowman, B Walker, BD Kwon, DS Lazarevic, V Glimcher, LH AF Adoro, Stanley Cubillos-Ruiz, Juan R. Chen, Xi Deruaz, Maud Vrbanac, Vladimir D. Song, Minkyung Park, Suna Murooka, Thomas T. Dudek, Timothy E. Luster, Andrew D. Tager, Andrew M. Streeck, Hendrik Bowman, Brittany Walker, Bruce D. Kwon, Douglas S. Lazarevic, Vanja Glimcher, Laurie H. TI IL-21 induces antiviral microRNA-29 in CD4 T cells to limit HIV-1 infection SO NATURE COMMUNICATIONS LA English DT Article ID CHRONIC VIRAL-INFECTION; IN-VIVO; TRANSCRIPTION FACTORS; REPLICATION CAPACITY; CELLULAR MICRORNA; HUMANIZED MICE; EXPRESSION; DEPLETION; TRANSMISSION; RESPONSES AB Initial events after exposure determine HIV-1 disease progression, underscoring a critical need to understand host mechanisms that interfere with initial viral replication. Although associated with chronic HIV-1 control, it is not known whether interleukin-21 (IL-21) contributes to early HIV-1 immunity. Here we take advantage of tractable primary human lymphoid organ aggregate cultures to show that IL-21 directly suppresses HIV-1 replication, and identify microRNA-29 (miR-29) as an antiviral factor induced by IL-21 in CD4 T cells. IL-21 promotes transcription of all miR-29 species through STAT3, whose binding to putative regulatory regions within the MIR29 gene is enriched by IL-21 signalling. Notably, exogenous IL-21 limits early HIV-1 infection in humanized mice, and lower viremia in vivo is associated with higher miR-29 expression. Together, these findings reveal a novel antiviral IL-21-miR-29 axis that promotes CD4 T-cell-intrinsic resistance to HIV-1 infection, and suggest a role for IL-21 in initial HIV-1 control in vivo. C1 [Adoro, Stanley; Cubillos-Ruiz, Juan R.; Chen, Xi; Song, Minkyung; Park, Suna; Glimcher, Laurie H.] Cornell Univ, Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Adoro, Stanley; Cubillos-Ruiz, Juan R.; Vrbanac, Vladimir D.; Dudek, Timothy E.; Tager, Andrew M.; Bowman, Brittany; Walker, Bruce D.; Kwon, Douglas S.; Glimcher, Laurie H.] MIT & Harvard, Ragon Inst MGH, Cambridge, MA 02139 USA. [Deruaz, Maud; Vrbanac, Vladimir D.; Murooka, Thomas T.; Luster, Andrew D.; Tager, Andrew M.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Streeck, Hendrik] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Biol, D-45147 Essen, Germany. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20814 USA. [Lazarevic, Vanja] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Glimcher, LH (reprint author), Cornell Univ, Weill Cornell Med Coll, Dept Med, 1300 York Ave, New York, NY 10065 USA. EM lglimche@med.cornell.edu OI Chen, Xi/0000-0002-7995-6202 FU Ragon Institute of MGH, MIT and Harvard; CFAR Scholar Award; Ragon Institute; Harvard University Center for AIDS Research [NIAID P30AI060354]; National Institutes of Allergy and Infectious Disease [1R21AI087475-01] FX We thank Fabio Martinon, Matthew Greenblatt and Sarah Bettigole for critical reading of the manuscript and helpful discussions; John Moore and Thomas Ketas (Weill Cornell Medical College) for providing primary HIV-1 isolates, HIV-1NL4-3 and HIV-1NL4-3-luciferase virus supernatants. S.A., J.R.C-R. and M.D. were supported by Postdoctoral Fellowship Awards from the Ragon Institute of MGH, MIT and Harvard. T.T.M. was supported by the CFAR Scholar Award. The MGH Humanized Mouse Program (V.D.V., A.D.L. and A.M.T.) was supported by a Platform Award from the Ragon Institute and the Harvard University Center for AIDS Research grant NIAID P30AI060354. This study was supported by grants from the National Institutes of Allergy and Infectious Disease (1R21AI087475-01) and the Ragon Institute of MGH, MIT and Harvard to L.H.G. NR 67 TC 6 Z9 6 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2015 VL 6 AR 7562 DI 10.1038/ncomms8562 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL7VS UT WOS:000357180800001 PM 26108174 ER PT J AU Chabaud, M Heuze, ML Bretou, M Vargas, P Maiuri, P Solanes, P Maurin, M Terriac, E Le Berre, M Lankar, D Piolot, T Adelstein, RS Zhang, YF Sixt, M Jacobelli, J Benichou, O Voituriez, R Piel, M Lennon-Dumenil, AM AF Chabaud, Melanie Heuze, Melina L. Bretou, Marine Vargas, Pablo Maiuri, Paolo Solanes, Paola Maurin, Mathieu Terriac, Emmanuel Le Berre, Mael Lankar, Danielle Piolot, Tristan Adelstein, Robert S. Zhang, Yingfan Sixt, Michael Jacobelli, Jordan Benichou, Olivier Voituriez, Raphael Piel, Matthieu Lennon-Dumenil, Ana-Maria TI Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells SO NATURE COMMUNICATIONS LA English DT Article ID INVARIANT CHAIN; DOWN-REGULATION; MACROPINOCYTOSIS; RECEPTOR; PHAGOCYTOSIS; TRAFFICKING; BACTERIA; ADHESION; CDC42 AB The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space. C1 [Chabaud, Melanie; Heuze, Melina L.; Bretou, Marine; Vargas, Pablo; Solanes, Paola; Maurin, Mathieu; Lankar, Danielle; Lennon-Dumenil, Ana-Maria] Inst Curie, INSERM, U932, F-75248 Paris 05, France. [Maiuri, Paolo; Terriac, Emmanuel; Le Berre, Mael; Piel, Matthieu] Inst Curie, UMR144, CNRS, F-75248 Paris 05, France. [Piolot, Tristan] Inst Curie, Inserm U934, CNRS UMR3215, F-75248 Paris 05, France. [Adelstein, Robert S.; Zhang, Yingfan] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. [Sixt, Michael] IST Austria, A-3400 Klosterneuburg, Austria. [Jacobelli, Jordan] Natl Jewish Hlth & Univ Colorado, Denver, CO USA. [Benichou, Olivier; Voituriez, Raphael] Univ Paris 06, CNRS UMR 7600, F-7600 Paris, France. [Voituriez, Raphael] Univ Paris 06, CNRS FRE 3231, F-75005 Paris, France. RP Piel, M (reprint author), Inst Curie, UMR144, CNRS, 26 Rue Ulm, F-75248 Paris 05, France. EM mpiel@curie.fr; amlennon@curie.fr RI Le Berre, Mael/E-3538-2010; Lennon-Dumenil, Ana-Maria/I-6716-2016; OI Le Berre, Mael/0000-0002-2293-3659; VARGAS, Pablo/0000-0002-6475-494X; Sixt, Michael/0000-0002-6620-9179; Adelstein, Robert/0000-0002-8683-2144; Maiuri, Paolo/0000-0001-5079-445X FU Fondation pour la Recherche Medicale; Association pour la Recherche contre le Cancer; City of Paris; European Research Council [Strapacemi 243103]; Association Nationale pour la Recherche [ANR-09-PIRI-0027-PCVI]; InnaBiosante foundation (Micemico); DCBIOL Labex from the French Government [ANR-10-IDEX-0001-02-PSL*, ANR-11-LABX-0043]; ERC Advanced Investigator Grant (Institut Curie) [250367, CNRS UMR3215/Inserm U934] FX We thank S. Amigorena, N. Manel, Y. Bellaiche, S. Miserey-Lenkei and D. Obino for critical reading of the manuscript. We acknowledge the PICT IBiSA Nikon imaging centre (CNRS UMR144, Institut Curie), the Curie animal facility, O. Malbec and F.X. Gobert for technical support, A. Chaillet for his help with image analysis, H. Ploegh and O. Bakke for providing I-Abbeta-GFP mice and human Ii constructs, respectively. M.C. and M.L.H. were supported by fellowships from the Fondation pour la Recherche Medicale and the Association pour la Recherche contre le Cancer, respectively. This work was funded by grants from the City of Paris and the European Research Council to A.-M.L.-D. (Strapacemi 243103), the Association Nationale pour la Recherche (ANR-09-PIRI-0027-PCVI) and the InnaBiosante foundation (Micemico) to A.-M.L.-D., M.P. and R.V., and the DCBIOL Labex from the French Government (ANR-10-IDEX-0001-02-PSL* and ANR-11-LABX-0043). The super-resolution SIM microscope was funded through an ERC Advanced Investigator Grant (250367) to Edith Heard (CNRS UMR3215/Inserm U934, Institut Curie). NR 47 TC 14 Z9 14 U1 3 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2015 VL 6 AR 7526 DI 10.1038/ncomms8526 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL7VG UT WOS:000357179400003 PM 26109323 ER PT J AU Lee, JEA Mitchell, NC Zaytseva, O Chahal, A Mendis, P Cartier-Michaud, A Parsons, LM Poortinga, G Levens, DL Hannan, RD Quinn, LM AF Lee, Jue Er Amanda Mitchell, Naomi C. Zaytseva, Olga Chahal, Arjun Mendis, Peter Cartier-Michaud, Amandine Parsons, Linda M. Poortinga, Gretchen Levens, David L. Hannan, Ross D. Quinn, Leonie M. TI Defective Hfp-dependent transcriptional repression of dMYC is fundamental to tissue overgrowth in Drosophila XPB models SO NATURE COMMUNICATIONS LA English DT Article ID RNA-POLYMERASE-II; MYC MESSENGER-RNA; C-MYC; XERODERMA-PIGMENTOSUM; DNA-REPAIR; CELL-CYCLE; REGULATES DMYC; INTERACTING REPRESSOR; COCKAYNE-SYNDROME; EXCISION-REPAIR AB Nucleotide excision DNA repair (NER) pathway mutations cause neurodegenerative and progeroid disorders (xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD)), which are inexplicably associated with (XP) or without (CS/TTD) cancer. Moreover, cancer progression occurs in certain patients, but not others, with similar C-terminal mutations in the XPB helicase subunit of transcription and NER factor TFIIH. Mechanisms driving overproliferation and, therefore, cancer associated with XPB mutations are currently unknown. Here using Drosophila models, we provide evidence that C-terminally truncated Hay/XPB alleles enhance overgrowth dependent on reduced abundance of RNA recognition motif protein Hfp/FIR, which transcriptionally represses the MYC oncogene homologue, dMYC. The data demonstrate that dMYC repression and dMYC-dependent overgrowth in the Hfp hypomorph is further impaired in the C-terminal Hay/XPB mutant background. Thus, we predict defective transcriptional repression of MYC by the Hfp orthologue, FIR, might provide one mechanism for cancer progression in XP/CS. C1 [Lee, Jue Er Amanda; Mitchell, Naomi C.; Zaytseva, Olga; Chahal, Arjun; Mendis, Peter; Parsons, Linda M.; Quinn, Leonie M.] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3010, Australia. [Cartier-Michaud, Amandine] Aix Marseille Univ, F-13284 Marseille, France. [Poortinga, Gretchen; Hannan, Ross D.] Peter MacCallum Canc Ctr, East Melbourne, Vic 3002, Australia. [Levens, David L.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hannan, Ross D.] Australian Natl Univ, John Curtin Sch Med Res, Dept Canc Biol & Therapeut, Canberra, ACT 2600, Australia. RP Quinn, LM (reprint author), Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3010, Australia. EM l.quinn@unimelb.edu.au RI Levens, David/C-9216-2009; OI Levens, David/0000-0002-7616-922X; Hannan, Ross/0000-0002-2166-4493 FU National Health and Medical Research Council of Australia; Cancer Council of Victoria FX We thank M. Fuller and M. Zurita for the Haywire strains. We are grateful to the Bloomington and VDRC stock centres for Drosophila strains and to the DSHB for antibodies. This work was funded by Project Grants and a Senior Research Fellowship from the National Health and Medical Research Council of Australia. This work was also supported by the Cancer Council of Victoria. NR 70 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2015 VL 6 AR 7404 DI 10.1038/ncomms8404 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL7TX UT WOS:000357175700006 PM 26074141 ER PT J AU Kucharski, AJ Conlan, AJK Eames, KTD AF Kucharski, Adam J. Conlan, Andrew J. K. Eames, Ken T. D. TI School's Out: Seasonal Variation in the Movement Patterns of School Children SO PLOS ONE LA English DT Article ID INFECTIOUS-DISEASE; SOCIAL NETWORKS; MIXING PATTERNS; SPREAD; INFLUENZA; TRANSMISSION; IMPACT; EPIDEMIC; BEHAVIOR; CONTACTS AB School children are core groups in the transmission of many common infectious diseases, and are likely to play a key role in the spatial dispersal of disease across multiple scales. However, there is currently little detailed information about the spatial movements of this epidemiologically important age group. To address this knowledge gap, we collaborated with eight secondary schools to conduct a survey of movement patterns of school pupils in primary and secondary schools in the United Kingdom. We found evidence of a significant change in behaviour between term time and holidays, with term time weekdays characterised by predominately local movements, and holidays seeing much broader variation in travel patterns. Studies that use mathematical models to examine epidemic transmission and control often use adult commuting data as a proxy for population movements. We show that while these data share some features with the movement patterns reported by school children, there are some crucial differences between the movements of children and adult commuters during both term- time and holidays. C1 [Kucharski, Adam J.; Eames, Ken T. D.] London Sch Hyg & Trop Med, Ctr Math Modelling Infect Dis, London WC1, England. [Kucharski, Adam J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Conlan, Andrew J. K.] Univ Cambridge, Dept Vet Med, Dis Dynam Unit, Cambridge, England. RP Kucharski, AJ (reprint author), London Sch Hyg & Trop Med, Ctr Math Modelling Infect Dis, London WC1, England. EM adam.kucharski@lshtm.ac.uk FU Medical Research Council [MR/K021524/1]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Alborada Trust; NIHR [CDF-2011-04-019] FX AJK was supported by the Medical Research Council (fellowship MR/K021524/1, http://www.mrc.ac.uk/) and the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health (http://www.fic.nih.gov/about/staff/pages/epidemiology-population.aspx#r apidd). AJKC was supported by the Alborada Trust (http://www.alboradatrust.com/). KTDE was supported by the NIHR (CDF-2011-04-019, http://www.nihr.ac.uk/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 2 Z9 2 U1 1 U2 7 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 1 PY 2015 VL 10 IS 6 AR e0128070 DI 10.1371/journal.pone.0128070 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL0KF UT WOS:000356630900108 PM 26030611 ER PT J AU Barciszewski, J Marquez, VE Vasseur, JJ Markiewicz, WT AF Barciszewski, Jan Marquez, Victor E. Vasseur, Jean-Jacques Markiewicz, Wojciech T. TI Chemical Biology of Nucleic Acids SO ACS CHEMICAL BIOLOGY LA English DT Editorial Material ID ANTICANCER AGENTS; INHIBITORS; ANALOGS C1 [Barciszewski, Jan; Markiewicz, Wojciech T.] Polish Acad Sci, Inst Bioorgan Chem, PL-61704 Poznan, Poland. [Marquez, Victor E.] NIH, Biol Chem Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Vasseur, Jean-Jacques] Univ Montpellier, Inst Biomol Max Mousseron, F-33095 Montpellier, France. RP Markiewicz, WT (reprint author), Polish Acad Sci, Inst Bioorgan Chem, PL-61704 Poznan, Poland. EM markwt@ibch.poznan.pl OI Vasseur, Jean-Jacques/0000-0002-4379-6139 NR 18 TC 0 Z9 0 U1 4 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JUN PY 2015 VL 10 IS 6 BP 1358 EP 1361 DI 10.1021/acschembio.5b00320 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CL3JE UT WOS:000356845400001 PM 26087829 ER PT J AU Ortiz-Meoz, RF Jiang, JY Lazarus, MB Orman, M Janetzko, J Fan, CG Duveau, DY Tan, ZW Thomas, CJ Walker, S AF Ortiz-Meoz, Rodrigo F. Jiang, Jiaoyang Lazarus, Michael B. Orman, Marina Janetzko, John Fan, Chenguang Duveau, Damien Y. Tan, Zhi-Wei Thomas, Craig J. Walker, Suzanne TI A Small Molecule That Inhibits OGT Activity in Cells SO ACS CHEMICAL BIOLOGY LA English DT Article ID O-GLCNAC TRANSFERASE; BETA-N-ACETYLGLUCOSAMINE; LINKED GLYCOSYLATION; CHRONIC DISEASE; CANCER CELLS; GLCNACYLATION; METABOLISM; GLYCOSYLTRANSFERASE; PATHWAY; STRESS AB O-GlcNAc transferase (OGT) is at essential mammalian enzyme that regulates numerous cellular processes through the attachment of O-linked N-acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. Its targets include kinases, phosphatases, transcription factors, histones, and many other intracellular proteins. The biology of O-GlcNAc modification is. still not well understood, and cell-permeable inhibitors of OGT are needed both as research tools and for validating OGT as a therapeutic target. Here, we report a aria molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit. It is cell-permeable and inhibits protein O-GlcNACylation in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. The development of this molecule validates high-throughput screening approaches for the, discovery of glycosyltransferase inhibitors, and further optimization of this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT in animal models. C1 [Ortiz-Meoz, Rodrigo F.; Jiang, Jiaoyang; Lazarus, Michael B.; Orman, Marina; Janetzko, John; Fan, Chenguang; Tan, Zhi-Wei; Walker, Suzanne] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02138 USA. [Duveau, Damien Y.; Thomas, Craig J.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA. RP Walker, S (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02138 USA. EM Suzanne_walker@hms.harvard.edu OI Janetzko, John/0000-0003-1604-2515 FU Division of Preclinical Innovation, National Center for Advancing Translational Sciences; Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research [U54CA143930]; National Institutes of Health [GM094263, GM100539]; NSERC PGS-M fellowship; NSERC D3 fellowship; [5 T32 GM095450-04] FX This research was supported by the Division of Preclinical Innovation, National Center for Advancing Translational Sciences, the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research, grant #U54CA143930 and the National Institutes of Health (GM094263 to S.W. and GM100539 to R.F.O.-M.). M.O. was supported by training grant 5 T32 GM095450-04. J.J. was supported by NSERC PGS-M and D3 fellowships. We thank D. Vocadlo for generously providing UDP-5SGlcNAc, Ac4-5SGlcNAc, and thoughtful comments on the manuscript. We also thank J. Gildersleeve for helpful advice on lectin specificity. NR 43 TC 18 Z9 18 U1 9 U2 39 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JUN PY 2015 VL 10 IS 6 BP 1392 EP 1397 DI 10.1021/acschembio.5b00004 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CL3JE UT WOS:000356845400005 PM 25751766 ER PT J AU Blazer, LL Storaska, AJ Jutkiewicz, EM Turner, EM Calcagno, M Wade, SM Wang, Q Huang, XP Traynor, JR Husbands, SM Morari, M Neubig, RR AF Blazer, Levi L. Storaska, Andrew J. Jutkiewicz, Emily M. Turner, Emma M. Calcagno, Mariangela Wade, Susan M. Wang, Qin Huang, Xi-Ping Traynor, John R. Husbands, Stephen M. Morari, Michele Neubig, Richard R. TI Selectivity and Anti-Parkinson's Potential of Thiadiazolidinone RGS4 Inhibitors SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Regulator of G-protein signaling; Parkinson's disease; PPI; RGS; protein-protein interaction; thiadiazolidinone ID PROTEIN INTERACTION INHIBITORS; SMALL-MOLECULE INHIBITORS; DRUG DISCOVERY; OPIOID RECEPTOR; SIGNALING PROTEINS; COUPLED RECEPTORS; INTERACTION ASSAY; L-DOPA; REGULATORS; TARGETS AB Many current therapies target G protein coupled receptors (GPCR), transporters, or ion channels. In addition to directly targeting these proteins, disrupting the protein protein interactions that localize or regulate their function could enhance selectivity and provide unique pharmacologic actions. Regulators of G protein signaling (RGS) proteins, especially RGS4, play significant roles in epilepsy and Parkinson's disease. Thiadiazolidinone (TDZD) inhibitors of RGS4 are nanomolar potency blockers of the biochemical actions of RGS4 in vitro. Here, we demonstrate the substantial selectivity (8- to >5000-fold) of CCG-203769 for RGS4 over other RGS proteins. It is also 300-fold selective for RGS4 over GSK-3 beta another target of this class of chemical scaffolds. It does not inhibit the cysteine protease papain at 100 mu M. CCG-203769 enhances G alpha(q)-dependent cellular Ca2+ signaling in an RGS4-dependent manner. TDZD inhibitors also enhance G alpha(i)-dependent delta-OR inhibition of cAMP production in SH-SY-5Y cells, which express endogenous receptors and RGS4. Importantly, CCG-203769 potentiates the known RGS4 mechanism of G alpha(i)-dependent muscarinic bradycardia in vivo. Furthermore, it reverses raclopride-induced akinesia and bradykinesia in mice, a model of some aspects of the movement disorder in Parkinson's disease. A broad assessment of compound effects revealed minimal off-target effects at concentrations necessary for cellular RGS4 inhibition. These results expand our understanding of the mechanism and specificity of TDZD RGS inhibitors and support the potential for therapeutic targeting of RGS proteins in Parkinson's disease and other neural disorders. C1 [Blazer, Levi L.; Storaska, Andrew J.; Jutkiewicz, Emily M.; Wade, Susan M.; Wang, Qin; Traynor, John R.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Storaska, Andrew J.; Neubig, Richard R.] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA. [Turner, Emma M.; Husbands, Stephen M.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. [Calcagno, Mariangela; Morari, Michele] Univ Ferrara, Dept Med Sci, Pharmacol Sect, I-44121 Ferrara, Italy. [Huang, Xi-Ping] Univ N Carolina, NIMH, PDSP, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Blazer, LL (reprint author), Michigan State Univ, Dept Pharmacol & Toxicol, B440 Life Sci,1355 Bogue St, E Lansing, MI 48824 USA. EM rneubig@msu.edu.edu OI Husbands, Stephen/0000-0002-9928-6322 FU NIH [RO1 DA023252]; Chemical Biology Interface training program [NIH T32GM008597]; Michigan Diabetes Research and Training Center [NIH P60 DK020572]; University of Michigan Comprehensive Cancer Center Support Grant [NIH P30 CA046592] FX Funding was provided by NIH RO1 DA023252 (to R.R.N.), the Chemical Biology Interface training program (NIH T32GM008597) (to L.L.B.) and core facilities supported by the Michigan Diabetes Research and Training Center (NIH P60 DK020572), and University of Michigan Comprehensive Cancer Center Support Grant NIH P30 CA046592. NR 46 TC 11 Z9 11 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD JUN PY 2015 VL 6 IS 6 BP 911 EP 919 DI 10.1021/acschemneuro.5b00063 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA CL2FC UT WOS:000356758000012 PM 25844489 ER PT J AU Warady, BA Abraham, AG Schwartz, GJ Wong, CS Munoz, A Betoko, A Mitsnefes, M Kaskel, F Greenbaum, LA Mak, RH Flynn, J Moxey-Mims, MM Furth, S AF Warady, Bradley A. Abraham, Alison G. Schwartz, George J. Wong, Craig S. Munoz, Alvaro Betoko, Aisha Mitsnefes, Mark Kaskel, Frederick Greenbaum, Larry A. Mak, Robert H. Flynn, Joseph Moxey-Mims, Marva M. Furth, Susan TI Predictors of Rapid Progression of Glomerular and Nonglomerular Kidney Disease in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Pediatric; children; adolescents; chronic kidney disease (CKD); disease progression; disease trajectory; risk factor; glomerular filtration rate (GFR); proteinuria; urinary protein-creatinine ratio (UPCR); end-stage renal disease (ESRD); renal replacement therapy (RRT); Chronic Kidney Disease in Children (CKiD) Study ID LOW-PROTEIN DIET; BLOOD-PRESSURE; RISK-FACTORS; HYPODYSPLASTIC NEPHROPATHY; ITALKID PROJECT; RENAL-FAILURE; CKD PATIENTS; ASSOCIATION; PHOSPHATE; DECLINE AB Background: Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression. Study Design: Prospective multicenter observational cohort study. Setting & Participants: 496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Predictors: Proteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia. Outcomes: Parametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR). Results: 398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2 mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2 mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally. Limitations: Small number of events in glomerular patients and use of internal cross-validation. Conclusions: Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to renal replacement therapy or 50% decline in GFR in children with CKD. (C) 2015 by the National Kidney Foundation, Inc. C1 [Warady, Bradley A.] Childrens Mercy Hosp, Div Pediat Nephrol, Kansas City, MO 64108 USA. [Abraham, Alison G.; Munoz, Alvaro; Betoko, Aisha] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Schwartz, George J.] Univ Rochester, Rochester, NY USA. [Wong, Craig S.] Univ New Mexico, Childrens Hosp, Albuquerque, NM 87131 USA. [Mitsnefes, Mark] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Kaskel, Frederick] Childrens Hosp Montefiore, New York, NY USA. [Greenbaum, Larry A.] Emory Univ, Atlanta, GA 30322 USA. [Greenbaum, Larry A.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Mak, Robert H.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Flynn, Joseph] Seattle Childrens Hosp, Seattle, WA USA. [Moxey-Mims, Marva M.] NIDDK, NIH, Bethesda, MD 20892 USA. [Furth, Susan] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Warady, BA (reprint author), Childrens Mercy Hosp, 2401 Gillham Rd, Kansas City, MO 64108 USA. EM bwarady@cmh.edu OI Betoko, Aisha/0000-0003-1245-8257 FU NCATS NIH HHS [UL1 TR001425]; NIDDK NIH HHS [U01-DK-66143, U01 DK066116, U01 DK066143, U01 DK066174, U01 DK082194, U01-DK-66116, U01-DK-66174, U01DK-082194] NR 44 TC 20 Z9 21 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUN PY 2015 VL 65 IS 6 BP 878 EP 888 DI 10.1053/j.ajkd.2015.01.008 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA CL1TP UT WOS:000356728000012 PM 25799137 ER PT J AU DellaValle, CT Purdue, MP Ward, MH Locke, SJ Stewart, PA De Roos, AJ Hartge, P Rothman, N Friesen, MC AF DellaValle, Curt T. Purdue, Mark P. Ward, Mary H. Locke, Sarah J. Stewart, Patricia A. De Roos, Anneclaire J. Hartge, Patricia Rothman, Nathanial Friesen, Melissa C. TI Validity of Expert Assigned Retrospective Estimates of Occupational Polychlorinated Biphenyl Exposure SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE expert assessment; occupational exposure; polychlorinated biphenyls; validity ID NON-HODGKINS-LYMPHOMA; CARPET DUST; DETERMINANTS; RELIABILITY; INDUSTRY; RISK AB Assessment of retrospective exposures based on expert judgment in case-control studies is usually of unknown validity because of the difficulty in finding gold standards for comparison. We investigated the relationship between expert-assigned retrospective occupational polychlorinated biphenyl (PCB) exposure estimates and serum PCB concentrations. Analyses were conducted on a subset of cases (n = 94) and controls (n = 96) in the multi-center National Cancer Institute, Surveillance, Epidemiology, and End Results Case-Control Study of non-Hodgkin lymphoma. Based on the subjects' lifetime work histories, an industrial hygienist assigned each job a probability of PCB exposure [< 5% (unexposed), 5-<50% (possibly exposed), >= 50% (probably exposed)]. Ordinary least squares regression was used to investigate associations between the probability rating and log-transformed lipid-adjusted serum levels of 14 PCB congeners and total PCBs (GPCBs). Compared to unexposed participants (n = 163), those with a probably exposed job (n = 7) had serum levels that were 87% higher for GPCBs (95% confidence interval: 1.33-2.62) and 38% of serum level variability was explained by the probability rating. Statistically significant associations between probability ratings and serum levels for 12 of 14 individual congeners were also observed. In summary, the observed contrast in PCB serum levels by probability rating provides support for the occupational PCB exposure assessment. C1 [DellaValle, Curt T.; Purdue, Mark P.; Ward, Mary H.; Locke, Sarah J.; Rothman, Nathanial; Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA 22207 USA. [De Roos, Anneclaire J.] Drexel Univ, Dept Occupat & Environm Hlth, Sch Publ Hlth, Philadelphia, PA 19102 USA. [Hartge, Patricia] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP DellaValle, CT (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM curt.dellavalle@gmail.com RI Purdue, Mark/C-9228-2016; Friesen, Melissa/A-5362-2009 OI Purdue, Mark/0000-0003-1177-3108; FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health [Z01 CP10122, Z01 CP010120] FX This study was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (Z01 CP10122; Z01 CP010120). NR 18 TC 0 Z9 0 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 EI 1475-3162 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD JUN PY 2015 VL 59 IS 5 BP 609 EP 615 DI 10.1093/annhyg/mev001 PG 7 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA CL0JC UT WOS:000356627300009 PM 25737332 ER PT J AU Jalah, R Torres, OB Mayorov, AV Li, FY Antoline, JFG Jacobson, AE Rice, KC Deschamps, JR Beck, Z Alving, CR Matyas, GR AF Jalah, Rashmi Torres, Oscar B. Mayorov, Alexander V. Li, Fuying Antoline, Joshua F. G. Jacobson, Arthur E. Rice, Kenner C. Deschamps, Jeffrey R. Beck, Zoltan Alving, Carl R. Matyas, Gary R. TI Efficacy, but Not Antibody Titer or Affinity, of a Heroin Hapten Conjugate Vaccine Correlates with Increasing Hapten Densities on Tetanus Toxoid, but Not on CRM197 Carriers SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SUBSTANCE-ABUSE; GLYCOCONJUGATE VACCINES; MORPHINE/HEROIN VACCINE; PROTEIN; TOXIN; RATS; 6-MONOACETYLMORPHINE; IMMUNOGENICITY; DERIVATIVES; ADDICTION AB Vaccines against drugs of abuse have induced antibodies in animals that blocked the biological effects of the drug by sequestering the drug in the blood and preventing it from crossing the blood-brain barrier. Drugs of abuse are too small to induce antibodies and, therefore, require conjugation of drug hapten analogs to a carrier protein. The efficacy of these conjugate vaccines depends on several factors including hapten design, coupling strategy, hapten density, carrier protein selection, and vaccine adjuvant. Previously, we have shown that 1 (MorHap), a heroin/morphine hapten, conjugated to tetanus toxoid (TT) and mixed with liposomes containing monophosphoryl lipid A [L(MPLA)] as adjuvant, partially blocked the antinociceptive effects of heroin in mice. Herein, we extended those findings, demonstrating greatly improved vaccine induced antinociceptive effects up to 3% mean maximal potential effect (%MPE). This was obtained by evaluating the effects of vaccine efficacy of hapten 1 vaccine conjugates with varying hapten densities using two different commonly used carrier proteins, TT and cross-reactive material 197 (CRM197). Immunization of mice with these conjugates mixed with L(MPLA) induced very high anti-1 IgG peak levels of 400-1500 mu g/mL that bound to both heroin and its metabolites, 6-acetylmorphine and morphine. Except for the lowest hapten density for each carrier, the antibody titers and affinity were independent of hapten density. The TT carrier based vaccines induced long-lived inhibition of heroin-induced antinociception that correlated with increasing hapten density. The best formulation contained TT with the highest hapten density of >= 30 haptens/TT molecule and induced %MPE of approximately 3% after heroin challenge. In contrast, the best formulation using CRM197 was with intermediate 1 densities (10-15 haptens/CRM197 molecule), but the % MPE was approximately 13%. In addition, the chemical synthesis of 1, the optimization of the conjugation method, and the methods for the accurate quantification of hapten density are described. C1 [Jalah, Rashmi; Torres, Oscar B.; Mayorov, Alexander V.; Beck, Zoltan; Alving, Carl R.; Matyas, Gary R.] US Mil HIV Res Program, Lab Adjuvant & Antigen Res, Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. [Jalah, Rashmi; Torres, Oscar B.; Mayorov, Alexander V.] US Mil HIV Res Program, Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA. [Li, Fuying; Antoline, Joshua F. G.; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Mol Targets & Medicat Discovery Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Li, Fuying; Antoline, Joshua F. G.; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, Bethesda, MD 20892 USA. [Deschamps, Jeffrey R.] Naval Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. RP Matyas, GR (reprint author), US Mil HIV Res Program, Lab Adjuvant & Antigen Res, Walter Reed Army Inst Res, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM gmatyas@hivresearch.org RI Mayorov, Alexander/G-5204-2014; OI Mayorov, Alexander/0000-0002-0899-7138; Matyas, Gary/0000-0002-2074-2373 FU Henry M. Jackson Foundation for the Advancement of Military Medicine [W81XWH-07-2-067]; U.S. Army Medical Research and Materiel Command (MRMC) [W81XWH-07-2-067]; National Institute on Drug Abuse (NIH) [1DP1DA034787-01]; NIH Intramural Research Programs of the National Institute on Drug Abuse; National Institute of Alcohol Abuse and Alcoholism, NIH, DHHS; NIDA [Y1-DA1101]; Naval Research Laboratory (NRL) FX This work was supported through a Cooperative Agreement Award (no. W81XWH-07-2-067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Army Medical Research and Materiel Command (MRMC). The work was partially supported by an Avant Garde award to GRM from the National Institute on Drug Abuse (NIH grant no. 1DP1DA034787-01). The work of FL, JFGA, AEJ, and KCR was supported by the NIH Intramural Research Programs of the National Institute on Drug Abuse and the National Institute of Alcohol Abuse and Alcoholism, NIH, DHHS. The X-ray crystallographic work was supported by NIDA through an Interagency Agreement #Y1-DA1101 with the Naval Research Laboratory (NRL). The authors thank Drs. Klaus Gawrisch and Walter Teague (Laboratory of Membrane Biochemistry and Biophysics, NIAAA), for NMR spectral data; and Noel Whittaker (Mass Spectrometry Facility, NIDDK) for mass spectral data. The authors also thank Mr. Marcus Gallon, Ms. Elaine Morrison, Ms. Courtney Tucker, and Ms. Caroline Kittinger for providing outstanding technical assistance. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adhered to principles stated in the Guide for the Care and Use of Laboratory Animals, NRC Publication, 1996 edition. The views expressed in this article are those of the authors and do not necessarily reflect the official policy of the Department of the Army, Department of Defense, or NIH, or the U.S. Government. NR 49 TC 6 Z9 6 U1 2 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUN PY 2015 VL 26 IS 6 BP 1041 EP 1053 DI 10.1021/acs.bioconjchem.5b00085 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA CL2DS UT WOS:000356754400011 PM 25970207 ER PT J AU Weldon, JE Skarzynski, M Therres, JA Ostovitz, JR Zhou, H Kreitman, RJ Pastan, I AF Weldon, John E. Skarzynski, Martin Therres, Jamy A. Ostovitz, Joshua R. Zhou, Hong Kreitman, Robert J. Pastan, Ira TI Designing the Furin-Cleavable Linker in Recombinant Immunotoxins Based on Pseudomonas Exotoxin A SO BIOCONJUGATE CHEMISTRY LA English DT Article ID DISULFIDE-STABILIZED FV; B-CELL EPITOPES; PHASE-I TRIAL; MOXETUMOMAB PASUDOTOX; CYTOTOXIC ACTIVITY; LOW IMMUNOGENICITY; CHIMERIC TOXINS; MESOTHELIN; MALIGNANCIES; LEUKEMIA AB Recombinant immunotoxins (RITs) are fusion proteins that join antibodies to protein toxins for targeted cell killing. RITs aimed with Pseudomonas exotoxin A (PE) are undergoing clinical trials for the treatment of cancer. The current design of PE-based RITs joins an antibody fragment to the catalytic domain of PE using a polypeptide linker that is cleaved by the protease furin. Intracellular cleavage of native PE by furin is required for cytotoxicity, yet the PE cleavage site has been shown to be a poor furin substrate. Here we describe the rational design of more efficiently cleaved furin linkers in PE-based RITs, and experiments evaluating their effects on cleavage and cytotoxicity. We found that changes to the furin site could greatly influence both cleavage and cytotoxicity, but the two parameters were not directly correlated. Furthermore, the effects of alterations to the furin linker were not universal. Identical mutations in the anti-CD22 RIT HA22-LR often displayed different cytotoxicity from mutations in the anti-mesothelin RIT SS1-LR/GGS, underscoring the prominent role of the target site in their intoxication pathways. Combining several beneficial mutations in HA22-LR resulted in a variant (HA22-LR/FUR) with a remarkably enhanced cleavage rate and improved cytotoxicity against five B cell lines and similar or enhanced cytotoxicity in five out of six hairy cell leukemia patient samples. This result informs the design of protease-sensitive linkers and suggests that HA22-LR/FUR may be a candidate for further preclinical development. C1 [Weldon, John E.; Therres, Jamy A.; Ostovitz, Joshua R.] Towson Univ, Jess & Mildred Fisher Coll Sci & Math, Dept Biol Sci, Towson, MD 21252 USA. [Weldon, John E.; Skarzynski, Martin; Zhou, Hong; Kreitman, Robert J.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; Fisher College of Science and Mathematics, Towson University FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and in part by the Fisher College of Science and Mathematics, Towson University. NR 39 TC 3 Z9 3 U1 4 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUN PY 2015 VL 26 IS 6 BP 1120 EP 1128 DI 10.1021/acs.bioconjchem.5b00190 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA CL2DS UT WOS:000356754400020 PM 25997032 ER PT J AU Goldsmith, J Zipunnikov, V Schrack, J AF Goldsmith, Jeff Zipunnikov, Vadim Schrack, Jennifer TI Generalized multilevel function-on-scalar regression and principal component analysis SO BIOMETRICS LA English DT Article DE Accelerometry; Bayesian inference; Generalized functional data; Hamiltonian Monte Carlo; Penalized splines ID PHYSICAL-ACTIVITY; LONGITUDINAL DATA; MODELS; ACCELEROMETER; PATTERNS; BINARY; PCA AB This manuscript considers regression models for generalized, multilevel functional responses: functions are generalized in that they follow an exponential family distribution and multilevel in that they are clustered within groups or subjects. This data structure is increasingly common across scientific domains and is exemplified by our motivating example, in which binary curves indicating physical activity or inactivity are observed for nearly 600 subjects over 5 days. We use a generalized linear model to incorporate scalar covariates into the mean structure, and decompose subject-specific and subject-day-specific deviations using multilevel functional principal components analysis. Thus, functional fixed effects are estimated while accounting for within-function and within-subject correlations, and major directions of variability within and between subjects are identified. Fixed effect coefficient functions and principal component basis functions are estimated using penalized splines; model parameters are estimated in a Bayesian framework using Stan, a programming language that implements a Hamiltonian Monte Carlo sampler. Simulations designed to mimic the application have good estimation and inferential properties with reasonable computation times for moderate datasets, in both cross-sectional and multilevel scenarios; code is publicly available. In the application we identify effects of age and BMI on the time-specific change in probability of being active over a 24-hour period; in addition, the principal components analysis identifies the patterns of activity that distinguish subjects and days within subjects. C1 [Goldsmith, Jeff] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10027 USA. [Zipunnikov, Vadim] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Schrack, Jennifer] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Schrack, Jennifer] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Bethesda, MD 20892 USA. RP Goldsmith, J (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10027 USA. EM jeff.goldsmith@columbia.edu FU NIH, National Institute on Aging; National Heart, Lung, and Blood Institute [R01HL123407] FX We thank Luigi Ferrucci, Principal Investigator of the Baltimore Longitudinal Study on Aging, for encouraging the use of the BLSA accelerometer data that motivated this work and for his scientific insight and guidance. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. The second author's research is supported in part by Award R01HL123407 from the National Heart, Lung, and Blood Institute. NR 29 TC 7 Z9 7 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD JUN PY 2015 VL 71 IS 2 BP 344 EP 353 DI 10.1111/biom.12278 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA CL2XC UT WOS:000356810000011 PM 25620473 ER PT J AU Follmann, D Huang, CY AF Follmann, Dean Huang, Chiung-Yu TI Incorporating founder virus information in vaccine field trials SO BIOMETRICS LA English DT Article DE Burden of illness; Competing risks; Cox regression; Empirical process; Infectious disease; Marked process ID HIV-1 INFECTION; END-POINT; EFFICACY; MODELS; RATES AB Vaccine clinical trials with active surveillance for infection often use the time to infection as the primary endpoint. A common method of analysis for such trials is to compare the times to infection between the vaccine and placebo groups using a Cox regression model. With new technology, we can sometimes additionally record the precise number of virions that cause infection rather than just the indicator that infection occurred. In this article, we develop a unified approach for vaccine trials that couples the time to infection with the number of infecting or founder viruses. We assume that the instantaneous risk of a potentially infectious exposure for individuals in the placebo and vaccine groups follows the same proportional intensity model. Following exposure, the number of founder viruses X* is assumed to be generated from some distribution on 0,1,..., which is allowed to be different for the two groups. Exposures that result in X*=0 are unobservable. We denote the placebo and vaccine means of X* by and so that 1- measures the proportion reduction in the mean number of infecting virions due to vaccination per exposure. We develop different semi-parametric methods of estimating . We allow the distribution of X* to be Poisson or unspecified, and discuss how to incorporate covariates that impact the time to exposure and/or X*. Interestingly , which is a ratio of untruncated means, can be reliably estimated using truncated data (X*>0), even if the placebo and vaccine distributions of X* are completely unspecified. Simulations of vaccine clinical trials show that the method can reliably recover in realistic settings. We apply our methods to an HIV vaccine trial conducted in injecting drug users. C1 [Follmann, Dean] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Huang, Chiung-Yu] Johns Hopkins Univ, Div Biostat & Bioinformat, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. RP Follmann, D (reprint author), NIAID, Biostat Res Branch, 6700B Rockledge Dr MSC 7609, Bethesda, MD 20892 USA. EM dfollmann@niaid.nih.gov FU NCI NIH HHS [P30 CA006973] NR 21 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD JUN PY 2015 VL 71 IS 2 BP 386 EP 396 DI 10.1111/biom.12277 PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA CL2XC UT WOS:000356810000015 PM 25773491 ER PT J AU Jeffries, N Geller, NL AF Jeffries, Neal Geller, Nancy L. TI Longitudinal clinical trials with adaptive choice of follow-up time SO BIOMETRICS LA English DT Article DE Adaptive design; Adaptive follow-up time; Adaptive longitudinal trial; Longitudinal study; Model-free longitudinal analysis ID MULTIPLE END-POINTS; INTERIM ANALYSES; DESIGN AB In longitudinal studies comparing two treatments with a maximum follow-up time there may be interest in examining treatment effects for intermediate follow-up times. One motivation may be to identify the time period with greatest treatment difference when there is a non-monotone treatment effect over time; another motivation may be to make the trial more efficient in terms of time to reach a decision on whether a new treatment is efficacious or not. Here, we test the composite null hypothesis of no difference at any follow-up time versus the alternative that there is a difference at at least one follow-up time. The methods are applicable when a few measurements are taken over time, such as in early longitudinal trials or in ancillary studies. Suppose the test statistic Ztk will be used to test the hypothesis of no treatment effect at a fixed follow-up time tk. In this context a common approach is to perform a pilot study on N1 subjects, and evaluate the treatment effect at the fixed time points t1,...,tK and choose t* as the value of tk for which Ztk is maximized. Having chosen t* a second trial can be designed. In a setting with group sequential testing we consider several adaptive alternatives to this approach that treat the pilot and second trial as a seamless, combined entity and evaluate Type I error and power characteristics. The adaptive designs we consider typically have improved power over the common, separate trial approach. C1 [Jeffries, Neal; Geller, Nancy L.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Jeffries, N (reprint author), NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA. EM nealjeff@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 22 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD JUN PY 2015 VL 71 IS 2 BP 469 EP 477 DI 10.1111/biom.12287 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA CL2XC UT WOS:000356810000023 PM 25818116 ER PT J AU Mills, JL AF Mills, James L. TI Preventing folate-related neural tube defects: Problem solved, or not? SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Editorial Material ID FOLIC-ACID FORTIFICATION; UNITED-STATES C1 [Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Publ Hlth Res, NIH, Bethesda, MD USA. RP Mills, JL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Bethesda, MD 20892 USA. EM millsj@exchange.nih.gov FU Intramural NIH HHS NR 10 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUN PY 2015 VL 103 IS 6 BP 469 EP 470 DI 10.1002/bdra.23380 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA CL1AO UT WOS:000356674800001 PM 25884960 ER PT J AU Dauriz, M Porneala, BC Guo, XQ Bielak, LF Peyser, PA Durant, NH Carnethon, MR Bonadonna, RC Bonora, E Bowden, DW Florez, JC Fornage, M Hivert, MF Jacobs, DR Kabagambe, EK Lewis, CE Murabito, JM Rasmussen-Torvik, LJ Rich, SS Vassy, JL Yao, J Carr, JJ Kardia, SLR Siscovick, D O'Donnell, CJ Rotter, JI Dupuis, J Meigs, JB AF Dauriz, Marco Porneala, Bianca C. Guo, Xiuqing Bielak, Lawrence F. Peyser, Patricia A. Durant, Nefertiti H. Carnethon, Mercedes R. Bonadonna, Riccardo C. Bonora, Enzo Bowden, Donald W. Florez, Jose C. Fornage, Myriam Hivert, Marie-France Jacobs, David R., Jr. Kabagambe, Edmond K. Lewis, Cora E. Murabito, Joanne M. Rasmussen-Torvik, Laura J. Rich, Stephen S. Vassy, Jason L. Yao, Jie Carr, Jeffrey J. Kardia, Sharon L. R. Siscovick, David O'Donnell, Christopher J. Rotter, Jerome I. Dupuis, Josee Meigs, James B. TI Association of a 62 Variants Type 2 Diabetes Genetic Risk Score With Markers of Subclinical Atherosclerosis A Transethnic, Multicenter Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE cardiovascular disease; genetic association; risk assessment; type 2 diabetes mellitus ID CORONARY-ARTERY CALCIUM; GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; YOUNG-ADULTS; SUSCEPTIBILITY LOCI; MEDIA THICKNESS; PREVALENCE; MESA; HYPERTENSION; PROGRESSION AB Background Type 2 diabetes mellitus (T2D) and cardiovascular disease share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes mellitus. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. Methods and Results In a cross-sectional analysis, including 9210 European Americans, 3773 African Americans, 1446 Hispanic Americans, and 773 Chinese Americans without known cardiovascular disease and enrolled in the Framingham Heart Study, Coronary Artery Risk Development in Young Adults, Multi-Ethnic Study of Atherosclerosis, and Genetic Epidemiology Network of Arteriopathy studies, we tested a 62 T2D-loci genetic risk score for association with measures of SCA, including coronary artery or abdominal aortic calcium score, common and internal carotid artery intima-media thickness, and ankle-brachial index. We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors-adjusted model (significance, P<0.01=0.05/5, number of traits analyzed). An inverse association with coronary artery calcium score in Multi-Ethnic Study of Atherosclerosis Europeans (fully-adjusted P=0.004) and with common carotid artery intima-media thickness in the Framingham Heart Study (P=0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with -cell and insulin resistance genetic risk sub-scores in the Framingham Heart Study and in the Coronary Artery Risk Development in Young Adults. Conclusions SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and cardiovascular disease risk loci. C1 [Dauriz, Marco; Porneala, Bianca C.; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Florez, Jose C.; Hivert, Marie-France] Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. [Dauriz, Marco; Porneala, Bianca C.; Florez, Jose C.; Vassy, Jason L.; O'Donnell, Christopher J.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hivert, Marie-France] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Dauriz, Marco; Bonora, Enzo] Univ Verona, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, I-37100 Verona, Italy. [Dauriz, Marco; Bonora, Enzo] Hosp Trust Verona, Verona, Italy. [Guo, Xiuqing; Yao, Jie; Carr, Jeffrey J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Bielak, Lawrence F.; Peyser, Patricia A.; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Durant, Nefertiti H.] Univ Alabama Birmingham, Sch Med, Dept Pediat, Div Pediat & Adolescent Med, Birmingham, AL USA. [Carnethon, Mercedes R.; Rasmussen-Torvik, Laura J.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Bonadonna, Riccardo C.] Univ Parma, Sch Med, Div Endocrinol, Dept Clin & Expt Med, I-43100 Parma, Italy. [Bonadonna, Riccardo C.] AOI Parma, Parma, Italy. [Bowden, Donald W.] Wake Forest Sch Med, Ctr Diabet Res & Human Genom, Winston Salem, NC USA. [Bowden, Donald W.] Wake Forest Sch Med, Dept Biochem & Internal Med, Winston Salem, NC USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol & Metab, Sherbrooke, PQ J1K 2R1, Canada. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Kabagambe, Edmond K.] Vanderbilt Univ, Dept Med, Div Epidemiol, Nashville, TN USA. [Lewis, Cora E.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02215 USA. [Murabito, Joanne M.; O'Donnell, Christopher J.; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA. [Vassy, Jason L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Carr, Jeffrey J.] Wake Forest Univ Hlth Sci, Dept Radiol Sci, Winston Salem, NC USA. [Siscovick, David] New York Acad Med, New York, NY USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St 9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org RI Dauriz, Marco/S-5843-2016; OI Dauriz, Marco/0000-0002-5542-5941; BONORA, Enzo/0000-0003-1074-5164; Bonadonna, Riccardo/0000-0002-9809-1005 FU University of Verona; Massachusetts General Hospital-Harvard Medical School; National Institute of Health [U01 HG006500, L30 DK089597]; National Heart, Lung and Blood Institute's (NHLBI) [N01-HC-25195]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616]; NIDDK [K24 DK080140]; NIDDK Research Career Award [K23 DK65978]; Massachusetts General Hospital Physician Scientist Development Award; Doris Duke Charitable Foundation Clinical Scientist Development Award; NHLBI; University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging; MESA; NHLBI [N01-HC-65226]; National Center for Advancing Translational Sciences, CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]; National Institutes of Health from National Heart, Lung, Blood Institute [HL087660, HL100245]; [N01 HC-95159]; [N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167]; [N01-HC-95168]; [N01-HC-95169]; [N02-HL-64278]; [RR-024156] FX M. Dauriz was supported by research grants of the University of Verona and Massachusetts General Hospital-Harvard Medical School. J.L. Vassy was supported by U01 HG006500 and L30 DK089597 from National Institute of Health. The Framingham Heart Study: This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung and Blood Institute's (NHLBI) Framingham Heart Study (Contract No. N01-HC-25195). A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Also supported by National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK078616 to J.B. Meigs, NIDDK K24 DK080140 to J.B. Meigs, and NIDDK Research Career Award K23 DK65978, a Massachusetts General Hospital Physician Scientist Development Award, and a Doris Duke Charitable Foundation Clinical Scientist Development Award to J.C. Florez. The CARDIA Study: The CARDIA Study is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging. This article has been reviewed and approved by CARDIA for scientific content. The MESA Study: MESA and the MESA SHARe project are conducted and supported by the NHLBI in collaboration with MESA investigators. Support is provided by grants and contracts N01 HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, N02-HL-64278, and RR-024156. Funding for CARe genotyping was provided by NHLBI Contract N01-HC-65226. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. We thank the participants of the MESA study, the Coordinating Center, MESA investigators, and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The GENOA Study: Genetic Epidemiology Network of Arteriopathy (GENOA) study is supported by the National Institutes of Health, grant numbers HL087660 and HL100245 from National Heart, Lung, Blood Institute. We thank Eric Boerwinkle, PhD, and Megan L. Grove from the Human Genetics Center and Institute of Molecular Medicine and Division of Epidemiology, University of Texas Health Science Center, Houston, Texas, USA, and Julie Cunningham, PhD, from the Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA, for their help with genotyping.; No additional external funding was received for this study. The funders had no role in the design or preparation of the article. NR 55 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2015 VL 8 IS 3 BP 507 EP 515 DI 10.1161/CIRCGENETICS.114.000740 PG 9 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA CK7NI UT WOS:000356418800011 PM 25805414 ER PT J AU Dekker, JP Frank, KM AF Dekker, John P. Frank, Karen M. TI Salmonella, Shigella, and Yersinia SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Salmonella; Shigella; Yersinia; Enteric; Gram-negative bacilli; Gastroenteritis ID ENTERICA SEROVAR TYPHI; MULTILOCUS ENZYME ELECTROPHORESIS; GASTROINTESTINAL PATHOGEN PANEL; DESORPTION IONIZATION-TIME; FLIGHT MASS-SPECTROMETRY; COMPLETE GENOME SEQUENCE; MALDI-TOF MS; ESCHERICHIA-COLI; UNITED-STATES; SHIGA TOXIN AB Salmonella, Shigella, and Yersinia cause a well-characterized spectrum of disease in humans, ranging from asymptomatic carriage to hemorrhagic colitis and fatal typhoidal fever. These pathogens are responsible for millions of cases of food-borne illness in the United States each year, with substantial costs measured in hospitalizations and lost productivity. In the developing world, illness caused by these pathogens is not only more prevalent but also associated with a greater case-fatality rate. Classic methods for identification rely on selective media and serology, but newer methods based on mass spectrometry and polymerase chain reaction show great promise for routine clinical testing. C1 [Dekker, John P.; Frank, Karen M.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Frank, KM (reprint author), NIH, Dept Lab Med, Ctr Clin, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM karen.frank@nih.gov FU NIH FX This work was supported by the intramural research program, NIH. The views expressed are those of the authors and do not necessarily reflect those of NIH or HHS. NR 133 TC 2 Z9 2 U1 1 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 2015 VL 35 IS 2 BP 225 EP + DI 10.1016/j.cll.2015.02.002 PG 23 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CK9EV UT WOS:000356544300002 PM 26004640 ER PT J AU Glaze, ER Roy, MJ Dalrymple, LW Lanning, LL AF Glaze, Elizabeth R. Roy, Michael J. Dalrymple, Lonnie W. Lanning, Lynda L. TI A Comparison of the Pathogenesis of Marburg Virus Disease in Humans and Nonhuman Primates and Evaluation of the Suitability of These Animal Models for Predicting Clinical Efficacy under the 'Animal Rule' SO COMPARATIVE MEDICINE LA English DT Review ID ATTENUATED RECOMBINANT VACCINE; SANS-FRONTIERES INTERVENTION; HEMORRHAGIC-FEVER EPIDEMIC; CYNOMOLGUS MACAQUES; INFECTIOUS-DISEASES; AGENT DISEASE; EBOLA-VIRUS; GUINEA-PIGS; POSTEXPOSURE PROTECTION; FILOVIRUS INFECTIONS AB Marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. In addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. Healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as Marburg virus in order to test the efficacy of a therapy or preventive prior to licensure. When human efficacy studies are neither ethical nor feasible, the US Food and Drug Administration may grant marketing approval of a drug or biologic product under the 'Animal Rule,' through which demonstration of the efficacy of a product can be 'based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans.' This process requires that the pathogenic determinants of the disease in the animal model are similar to those that have been identified in humans. After reviewing primarily English-language, peer-reviewed journal articles, we here summarize the clinical manifestations of Marburg virus disease and the results of studies in NHP showing the characteristics and progression of the disease. We also include a detailed comparison of the characteristics of the human disease relative to those for NHP. This review reveals that the disease characteristics of Marburg virus disease are generally similar for humans and 3 NHP species: cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and African green monkeys (Chlorocebus aethiops). C1 [Glaze, Elizabeth R.; Lanning, Lynda L.] NIAID, NIH, Bethesda, MD 20892 USA. [Roy, Michael J.; Dalrymple, Lonnie W.] Leidos, Frederick, MD USA. RP Glaze, ER (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM glazee@mail.nih.gov NR 93 TC 2 Z9 2 U1 2 U2 10 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD JUN PY 2015 VL 65 IS 3 BP 241 EP 259 PG 19 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA CL7JA UT WOS:000357147100010 PM 26141449 ER PT J AU Kennedy, AP Epstein, DH Jobes, ML Agage, D Tyburski, M Phillips, KA Ali, AA Bari, R Hossain, SM Hovsepian, K Rahman, MM Ertin, E Kumar, S Preston, KL AF Kennedy, Ashley P. Epstein, David H. Jobes, Michelle L. Agage, Daniel Tyburski, Matthew Phillips, Karran A. Ali, Amin Ahsan Bari, Rummana Hossain, Syed Monowar Hovsepian, Karen Rahman, Md. Mahbubur Ertin, Emre Kumar, Santosh Preston, Kenzie L. TI Continuous in-the-field measurement of heart rate: Correlates of drug use, craving, stress, and mood in polydrug users SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cocaine; Heroin; Ambulatory physiological monitoring; Heart rate; Craving ID RATE-VARIABILITY; DEPENDENT INDIVIDUALS; INTRAVENOUS COCAINE; SMOKING-CESSATION; HUMANS; METHADONE; COMBINATION; NALTREXONE; RESPONSES; STIMULI AB Background: Ambulatory physiological monitoring could clarify antecedents and consequences of drug use and could contribute to a sensor-triggered mobile intervention that automatically detects behaviorally risky situations. Our goal was to show that such monitoring is feasible and can produce meaningful data. Methods: We assessed heart rate (HR) with AutoSense, a suite of biosensors that wirelessly transmits data to a smartphone, for up to 4 weeks in 40 polydrug users in opioid-agonist maintenance as they went about their daily lives. Participants also self-reported drug use, mood, and activities on electronic diaries. We compared HR with self-report using multilevel modeling (SAS Proc Mixed). Results: Compliance with AutoSense was good; the data yield from the wireless electrocardiographs was 85.7%. HR was higher when participants reported cocaine use than when they reported heroin use (F(2,9) = 250.3,p <.0001) and was also higher as a function of the dose of cocaine reported (F(1,8) = 207.7, p <.0001). HR was higher when participants reported craving heroin (F(1,16) = 230.9, p <.0001) or cocaine (F(1,14) = 157.2, p <.0001) than when they reported of not craving. HR was lower (p <.05) in randomly prompted entries in which participants reported feeling relaxed, feeling happy, or watching TV, and was higher when they reported feeling stressed, being hassled, or walking. Conclusions: High-yield, high-quality heart-rate data can be obtained from drug users in their natural environment as they go about their daily lives, and the resultant data robustly reflect episodes of cocaine and heroin use and other mental and behavioral events of interest. Published by Elsevier Ireland Ltd. C1 [Kennedy, Ashley P.; Epstein, David H.; Jobes, Michelle L.; Phillips, Karran A.; Preston, Kenzie L.] NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Agage, Daniel; Tyburski, Matthew] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Ali, Amin Ahsan; Bari, Rummana; Hossain, Syed Monowar; Rahman, Md. Mahbubur; Kumar, Santosh] Univ Memphis, Dept Comp Sci, Memphis, TN 38152 USA. [Hovsepian, Karen] Troy Univ, Dept Comp Sci, Troy, AL USA. [Ertin, Emre] Ohio State Univ, Dept Elect & Comp Engn, Columbus, OH 43210 USA. RP Preston, KL (reprint author), NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM kpreston@intra.nida.nih.gov RI Emchi, Karma/Q-1952-2016 FU National Institute on Drug Abuse Intramural Research Program; NSF [CNS-0910878, CNS-1212901, IIS-1231754]; NIH under Genes Environment and Health Initiative (GEI) [U01DA023812]; NIH under the Basic Behavioral and Social Sciences Research Opportunity Network (OppNet) [R01DA035502] FX This research was supported by the National Institute on Drug Abuse Intramural Research Program and NSF grants CNS-0910878 (funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)), CNS-1212901, IIS-1231754, and by NIH Grants U01DA023812 under Genes Environment and Health Initiative (GEI) and R01DA035502 under the Basic Behavioral and Social Sciences Research Opportunity Network (OppNet). The authors had sole responsibility for the design and conduct of the study, the analysis and interpretation of the data, and the preparation and review of the manuscript. NR 40 TC 3 Z9 3 U1 0 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2015 VL 151 BP 159 EP 166 DI 10.1016/j.drugalcdep.2015.03.024 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CL1WX UT WOS:000356736700019 PM 25920802 ER PT J AU Lee, JH Gamarel, KE Kahler, CW Marshall, BDL van den Berg, JJ Bryant, K Zaller, ND Operario, D AF Lee, Ji Hyun Gamarel, Kristi E. Kahler, Christopher W. Marshall, Brandon D. L. van den Berg, Jacob J. Bryant, Kendall Zaller, Nickolas D. Operario, Don TI Co-occurring psychiatric and drug use disorders among sexual minority men with lifetime alcohol use disorders SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol use; Men who have sex with men (MSM); Diagnostic co-occurrence ID NATIONAL EPIDEMIOLOGIC SURVEY; SUBSTANCE USE DISORDERS; UNITED-STATES; ANXIETY DISORDERS; BISEXUAL ADULTS; COMORBIDITY; PREVALENCE; ORIENTATION; HEALTH; GAY AB Background: Emerging evidence indicates multiple health risks associated with harmful alcohol use among sexual minority men in the United States. In particular, sexual minority men with alcohol use disorders (AUD) might have greater co-occurring health problems compared with heterosexual men. We used nationally representative data to compare the prevalence of diagnostic co-occurring psychiatric disorders and drug use disorders (DUD) among sexual minority men with AUD compared with heterosexual males with a lifetime AUD diagnosis. Methods: We analyzed data from 6899 adult males with AUD participating in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Using weighted multivariable logistic regression models, we compared the odds of lifetime diagnosis of mood disorders, anxiety disorders, and drug use disorders in sexual minority and heterosexual adult males with AUD. Results: Of participants included in this analysis, 176(2.6%) self-identified as a sexual minority. In adjusted analyses, sexual minority men with AUD were more likely than heterosexual men with AUD to have any mood disorder (including major depressive episode), any anxiety disorder (including panic disorder without agoraphobia, specific phobia, posttraumatic stress disorder, and generalized anxiety disorder), and lifetime DUD. Conclusions: The elevated co-occurrence of psychiatric disorders and DUD among sexual minority men with AUD suggests that future research is warranted. A better understanding of the etiology of diagnostic co-occurring mental health and substance use disorders among sexual minority men is needed in order to develop effective integrated prevention and treatment programs. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Lee, Ji Hyun; Kahler, Christopher W.; Marshall, Brandon D. L.; Operario, Don] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. [Gamarel, Kristi E.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [van den Berg, Jacob J.] Brown Univ, Miriam Hosp, Div Infect Dis, Providence, RI USA. [van den Berg, Jacob J.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Bryant, Kendall] NIAAA, Rockville, MD 20852 USA. [Zaller, Nickolas D.] Univ Arkansas, Fay W Boozman Coll Publ Hlth, Little Rock, AR 72204 USA. RP Operario, D (reprint author), Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. EM Don_Operario@brown.edu FU National Institute of Alcohol Abuse and Alcoholism [U24-AA022000, P01-AA019072]; National Institute of Allergy and Infectious Diseases [P30-AI042853]; National Institute for Mental Health [T32-MH07878] FX Role of funding source; Funding was provided by the National Institute of Alcohol Abuse and Alcoholism (grants U24-AA022000 and P01-AA019072), National Institute of Allergy and Infectious Diseases (grant P30-AI042853) and National Institute for Mental Health (grant T32-MH07878). NR 35 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2015 VL 151 BP 167 EP 172 DI 10.1016/j.drugalcdep.2015.03.018 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CL1WX UT WOS:000356736700020 PM 25913886 ER PT J AU Bruce, D Kahana, SY Bauermeister, JA Nichols, SL Hightow-Weidman, LB Heinze, JE Shea, J Fernandez, MI AF Bruce, Douglas Kahana, Shoshana Y. Bauermeister, Jose A. Nichols, Sharon L. Hightow-Weidman, Lisa B. Heinze, Justin E. Shea, Jaclyn Fernandez, M. Isabel CA Adolescent Med Trials Network HIV TI Neighborhood-level and individual-level correlates of cannabis use among young persons living with HIV/AIDS SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Youth; Cannabis (marijuana); Social disorganization; Neighborhood; Bisexual; HIV/AIDS ID ILLICIT DRUG-USE; HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-RISK BEHAVIORS; HIV-POSITIVE YOUTH; MARIJUANA USE; SUBSTANCE USE; ANTIRETROVIRAL THERAPY; PSYCHIATRIC-DISORDERS; SOCIOECONOMIC-STATUS; ADOLESCENT ALCOHOL AB Introduction: In addition to individual characteristics, there may be a wide range of environmental or neighborhood stressors that contribute to elevated cannabis use in groups of youth living with HIV/AIDS (YLHIV); however, the effects of social disorganization on cannabis use in YLHIV to date have not been studied. Methods: We examined the effects of individual-level and neighborhood-level factors by developing hierarchical generalized linear models estimating odds of current cannabis use (any use during the past 3 months) and daily cannabis use among a sample of YLHIV (N=1921) currently receiving medical care. Results: The final model for daily cannabis use in the past 3 months included significant positive effects associated with hostility (O.R. = 1.08, 95% C.I.: 1.05, 1.11), being older (O.R.= 1.12, 95% C.I.: 1.05, 1.20), being a bisexual male (O.R.= 1.72,95% C.I.: 1.10, 2.70), and residing in a community with a murder rate in the highest quartile (O.R. = 1.91,95% C.I.: 1.27, 2.87), second highest quartile (O.R.= 1.62,95% C.I.: 1.06, 2.46), or third highest quartile (O.R. = 1.52, 95% C.I.: 1.01, 2.30). Discussion: This paper advances our knowledge of the multilevel factors associated with elevated cannabis use among groups of YLHIV and furthers our understanding of social and structural determinants of health in this population. Future research into cannabis use among YLHIV should consider, not only cannabis use within the context of the adjustment of living with HIV/AIDS, but also the stressors that characterize the environments in which groups of YLHIV live. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Bruce, Douglas; Shea, Jaclyn] De Paul Univ, Dept Hlth Sci, Chicago, IL 60614 USA. [Kahana, Shoshana Y.] NIDA, Bethesda, MD 20892 USA. [Bauermeister, Jose A.; Heinze, Justin E.] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Nichols, Sharon L.] UC San Diego Sch Med, Dept Neurosci, San Diego, CA USA. [Hightow-Weidman, Lisa B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Div Infect Dis, Chapel Hill, NC USA. [Fernandez, M. Isabel] Nova SE Univ, Coll Osteopath Med, Davie, FL USA. RP Bruce, D (reprint author), De Paul Univ, Dept Hlth Sci, 1110W Belden,Suite 411, Chicago, IL 60614 USA. EM Dbruce1@depaul.edu OI Bauermeister, Jose/0000-0002-9276-2306 FU Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from the National Institutes of Health through the National Institute of Child Health and Human Development [U01 HD 040533, U01 HD 040474]; National Institute on Drug Abuse; National Institute on Mental Health [K01MH089838] FX This work was supported by The Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from the National Institutes of Health [U01 HD 040533 and U01 HD 040474] through the National Institute of Child Health and Human Development (B. Kapogiannis, S. Lee), with supplemental funding from the National Institutes on Drug Abuse (K. Davenny, S. Kahana) and Mental Health (P. Brouwers, S. Allison). Additional funding from the National Institute of Mental Health under grant K01MH089838 aided in the development of this paper. The NIH had no role in the study design; in the collection, analysis and interpretation of data; or in the writing of the manuscript. NR 62 TC 1 Z9 1 U1 7 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2015 VL 151 BP 173 EP 180 DI 10.1016/j.drugalcdep.2015.03.017 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CL1WX UT WOS:000356736700021 PM 25858786 ER PT J AU Cheung, GYC Villaruz, AE Joo, HS Duong, AC Yeh, AJ Nguyen, TH Sturdevant, DE Queck, SY Otto, M AF Cheung, Gordon Y. C. Villaruz, Amer E. Joo, Hwang-Soo Duong, Anthony C. Yeh, Anthony J. Nguyen, Thuan H. Sturdevant, Daniel E. Queck, S. Y. Otto, M. TI Genome-wide analysis of the regulatory function mediated by the small regulatory psm-mec RNA of methicillin-resistant Staphylococcus aureus (vol 304, pg 637, 2014) SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Correction C1 [Cheung, Gordon Y. C.; Villaruz, Amer E.; Joo, Hwang-Soo; Duong, Anthony C.; Yeh, Anthony J.; Nguyen, Thuan H.; Queck, S. Y.; Otto, M.] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. [Sturdevant, Daniel E.] NIAID, Genom Unit, Res Technol Branch, Rocky Mt Labs,NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1438-4221 EI 1618-0607 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD JUN-AUG PY 2015 VL 305 IS 4-5 BP 491 EP 491 DI 10.1016/j.ijmm.2015.03.006 PG 1 WC Microbiology; Virology SC Microbiology; Virology GA CL1WF UT WOS:000356734900007 ER PT J AU Kim, S Liu, HB Yeganova, LN Wilbur, WJ AF Kim, Sun Liu, Haibin Yeganova, Lana Wilbur, W. John TI Extracting drug-drug interactions from literature using a rich feature-based linear kernel approach SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Drug-drug interaction; Biomedical literature; Linear kernel approach ID PROTEIN INTERACTION EXTRACTION; BIOMEDICAL LITERATURE; NATURAL-LANGUAGE; CORPUS; TEXT AB Identifying unknown drug interactions is of great benefit in the early detection of adverse drug reactions. Despite existence of several resources for drug-drug interaction (DDI) information, the wealth of such information is buried in a body of unstructured medical text which is growing exponentially. This calls for developing text mining techniques for identifying DDIs. The state-of-the-art DDI extraction methods use Support Vector Machines (SVMs) with non-linear composite kernels to explore diverse contexts in literature. While computationally less expensive, linear kernel-based systems have not achieved a comparable performance in DDI extraction tasks. In this work, we propose an efficient and scalable system using a linear kernel to identify DDI information. The proposed approach consists of two steps: identifying DDIs and assigning one of four different DDI types to the predicted drug pairs. We demonstrate that when equipped with a rich set of lexical and syntactic features, a linear SVM classifier is able to achieve a competitive performance in detecting DDIs. In addition, the one-against-one strategy proves vital for addressing an imbalance issue in DDI type classification. Applied to the DDIExtraction 2013 corpus, our system achieves an F1 score of 0.670, as compared to 0.651 and 0.609 reported by the top two participating teams in the DDIExtraction 2013 challenge, both based on non-linear kernel methods. Published by Elsevier Inc. C1 [Kim, Sun; Liu, Haibin; Yeganova, Lana; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Liu, HB (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM sun.kim@nih.gov; haibin.liu@nih.gov; lana.yeganova@nih.gov; wilbur@ncbi.nlm.nih.gov FU Intramural Research Program of the NIH, National Library of Medicine FX The authors thank Isabel Segura-Bedmar for her help evaluating our preliminary results on the DDIExtraction 2013 dataset. Funding: This research was supported by the Intramural Research Program of the NIH, National Library of Medicine. NR 47 TC 11 Z9 12 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD JUN PY 2015 VL 55 BP 23 EP 30 DI 10.1016/j.jbi.2015.03.002 PG 8 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA CK9MR UT WOS:000356564700003 PM 25796456 ER PT J AU Ayvaz, S Horn, J Hassanzadeh, O Zhu, Q Stan, J Tatonetti, NP Vilar, S Brochhausen, M Samwald, M Rastegar-Mojarad, M Dumontier, M Boyce, RD AF Ayvaz, Serkan Horn, John Hassanzadeh, Oktie Zhu, Qian Stan, Johann Tatonetti, Nicholas P. Vilar, Santiago Brochhausen, Mathias Samwald, Matthias Rastegar-Mojarad, Majid Dumontier, Michel Boyce, Richard D. TI Toward a complete dataset of drug-drug interaction information from publicly available sources SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Drug-drug interaction; Record linkage; Natural language processing; Pharmacovigilance ID ELECTRONIC HEALTH RECORDS; METABOLISM; WIKIPEDIA; KNOWLEDGE; TOOL AB Although potential drug drug interactions (PDDIs) are a significant source of preventable drug-related harm, there is currently no single complete source of PDDI information. In the current study, all publically available sources of PDDI information that could be identified using a comprehensive and broad search were combined into a single dataset. The combined dataset merged fourteen different sources including 5 clinically-oriented information sources, 4 Natural Language Processing (NLP) Corpora, and 5 Bioinfor matics/Pharmacovigilance information sources. As a comprehensive PDDI source, the merged dataset might benefit the pharmacovigilance text mining community by making it possible to compare the representativeness of NLP corpora for PDDI text extraction tasks, and specifying elements that can be useful for future PDDI extraction purposes. An analysis of the overlap between and across the data sources showed that there was little overlap. Even comprehensive PDDI lists such as DrugBank, KEGG, and the NDF-RT had less than 50% overlap with each other. Moreover, all of the comprehensive lists had incomplete coverage of two data sources that focus on PDDIs of interest in most clinical settings. Based on this information, we think that systems that provide access to the comprehensive lists, such as APIs into RxNorm, should be careful to inform users that the lists may be incomplete with respect to PDDIs that drug experts suggest clinicians be aware of. In spite of the low degree of overlap, several dozen cases were identified where PDDI information provided in drug product labeling might be augmented by the merged dataset. Moreover, the combined dataset was also shown to improve the performance of an existing PDDI NLP pipeline and a recently published PDDI pharmacovigilance protocol. Future work will focus on improvement of the methods for mapping between PDDI information sources, identifying methods to improve the use of the merged dataset in PDDI NLP algorithms, integrating high-quality PDDI information from the merged dataset into Wikidata, and making the combined dataset accessible as Semantic Web Linked Data. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Ayvaz, Serkan] Kent State Univ, Dept Comp Sci, Kent, OH 44242 USA. [Horn, John] Univ Washington, Sch Pharm, Dept Pharm, Seattle, WA 98195 USA. [Horn, John] Univ Washington, Univ Washington Med, Serv Pharm, Seattle, WA 98195 USA. [Hassanzadeh, Oktie] IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA. [Zhu, Qian] Univ Maryland Baltimore Cty, Dept Informat Syst, Baltimore, MD 21250 USA. [Stan, Johann] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. [Tatonetti, Nicholas P.; Vilar, Santiago] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA. [Tatonetti, Nicholas P.; Vilar, Santiago] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA. [Tatonetti, Nicholas P.; Vilar, Santiago] Columbia Univ, Dept Med, New York, NY 10032 USA. [Brochhausen, Mathias] Univ Arkansas Med Sci, Div Biomed Informat, Little Rock, AR 72205 USA. [Samwald, Matthias] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, Sect Med Expert & Knowledge Based Syst, A-1090 Vienna, Austria. [Rastegar-Mojarad, Majid] Mayo Clin, Biomed Stat & Informat, Rochester, MN 55905 USA. [Dumontier, Michel] Stanford Ctr Biomed Informat Res, Stanford, CA 94305 USA. [Boyce, Richard D.] Dept Biomed Informat, Pittsburgh, PA 15206 USA. RP Ayvaz, S (reprint author), 2432 Echo Valley Dr, Stow, OH 44224 USA. EM sayvaz1@kent.edu; jrhorn@uw.edu; hassanzadeh@us.ibm.com; qianzhu@umbc.edu; johann.stan.phd@gmail.com; nick.tatonetti@columbia.edu; sav7003@dbmi.columbia.edu; mbrochhausen@uams.edu; matthias.samwald@meduniwien.ac.at; Mojarad.Majid@mayo.edu; michel.dumontier@stanford.edu; rdb20@pitt.edu OI Ayvaz, Serkan/0000-0003-2016-4443; Rastegar-Mojarad, Majid/0000-0001-6962-3554; Tatonetti, Nicholas/0000-0002-2700-2597 FU National Library of Medicine Grant [1R01LM011838-01]; National Institute on Aging [K01AG044433]; NIGMS [R01 GM107145]; Center for Expanded Data Annotation and Retrieval [NIH U54I117925]; Agency for Healthcare Research and Quality [K12HS019461]; NLM Research Participation Program; Austrian Science Fund (FWF) [PP 25608-N15] FX This work was supported primarily by National Library of Medicine Grant 1R01LM011838-01 and National Institute on Aging Grant K01AG044433. Additional support was provided by the NIGMS R01 GM107145, the Center for Expanded Data Annotation and Retrieval (NIH U54I117925), the Agency for Healthcare Research and Quality (K12HS019461), the NLM Research Participation Program (administered by the Oak Ridge Institute for Science and Education), and the Austrian Science Fund (FWF): [PP 25608-N15]. The content is solely the responsibility of the authors and does not represent the official views of the Agency for Healthcare Research and Quality or any of the other funding sources. NR 44 TC 12 Z9 12 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD JUN PY 2015 VL 55 BP 206 EP 217 DI 10.1016/j.jbi.2015.04.006 PG 12 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA CK9MR UT WOS:000356564700020 PM 25917055 ER PT J AU Xu, L Shan, SS Chen, YG Wane, XJ Nussinov, R Ma, BY AF Xu, Liang Shan, Shengsheng Chen, Yonggang Wane, Xiaojuan Nussinov, Ruth Ma, Buyong TI Coupling of Zinc-Binding and Secondary Structure in Nonfibrillar A beta 40 Peptide Oligomerization SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article; Proceedings Paper CT 10th International Conference on Chemical Structures (ICCS)/10th German Conference on Chemoinformatics (GCC) CY JUN 01-05, 2014 CL Noordwijkerhout, NETHERLANDS ID AMYLOID-BETA-PEPTIDE; MOLECULAR-DYNAMICS SIMULATIONS; ALZHEIMERS-DISEASE; ALPHA-HELIX; METAL-IONS; CONFORMATIONAL DISTRIBUTION; DIMERIZATION PROCESS; SHEET OLIGOMERS; DIMER FORMATION; ZN2+ BINDING AB Nonfibrillar neurotoxic amyloid beta (A beta) oligomer structures are typically rich in beta-sheets, which could be promoted by metal ions like Zn2+. Here, using molecular dynamics (MD) simulations, we systematically examined combinations of A beta 40 peptide conformations and Zn2+ binding modes to probe the effects of secondary structure on A beta dimerization energies and kinetics. We found that random conformations do not contribute to dimerization either thermodynamically or kinetically. Zn2+ couples with preformed secondary structures (alpha-helix and beta-hairpin) to speed dimerization and stabilize the resulting dimer. Partial a-helices increase the dimerization speed, and dimers with a-helix rich conformations have the lowest energy. When Zn2+ coordinates with residues D1, H6, H13, and H14, A beta 40 beta-hairpin monomers have the fastest dimerization speed. Dimers with experimentally observed zinc coordination (E11, H6, H13, and H14) form with slower rate but have lower energy. Zn2+ cannot stabilize fibril-like beta-arch dimers. However, Zn2+-bound beta-arch tetramers have the lowest energy. Collectively, zinc-stabilized beta-hairpin oligomers could be important in the nucleation-polymerization of cross-beta structures. Our results are consistent with experimental findings that a-helix to beta-structural transition should accompany A beta aggregation in the presence of zinc ions and that Zn2+ stabilizes nonfibrillar A beta oligomers and, thus, inhibits formation of less toxic A beta fibrils. C1 [Xu, Liang; Shan, Shengsheng] Dalian Univ Technol, Sch Chem, Dalian 116024, Peoples R China. [Chen, Yonggang] Dalian Univ Technol, Network & Informat Ctr, Dalian 116024, Peoples R China. [Wane, Xiaojuan] Dalian Univ Technol, Sch Chem Machinery, Dalian 116024, Peoples R China. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth; Ma, Buyong] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD 21702 USA. RP Xu, L (reprint author), Dalian Univ Technol, Sch Chem, Dalian 116024, Peoples R China. EM xuliang@dlut.edu.cn; mabuyong@mail.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Fundamental Research Funds for the Central Universities [DUT12LK38, 2100-852018]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research; China Scholarship Council FX Financial support from the Fundamental Research Funds for the Central Universities (grant no. DUT12LK38 and 2100-852018) is acknowledged. Computation time was provided by the High Performance Computing Department of Network and Information Center, Dalian University of Technology, and the high-performance computational facilities of the Biowulf PC/Linux cluster at the NIH. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. L.X. also thanks the China Scholarship Council for financial support. NR 118 TC 6 Z9 6 U1 5 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 EI 1549-960X J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD JUN PY 2015 VL 55 IS 6 BP 1218 EP 1230 DI 10.1021/acs.jcim.5b00063 PG 13 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA CL4DQ UT WOS:000356903200014 PM 26017140 ER PT J AU Lakatta, EG AF Lakatta, Edward G. TI So! What's aging? Is cardiovascular aging a disease? SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article ID RENIN-ANGIOTENSIN SYSTEM; MAJOR SHAREHOLDERS; TYPE-1 RECEPTOR; AEROBIC EXERCISE; IN-VITRO; RATS; ARTERIAL; AGE; HYPERTROPHY; ENTERPRISES AB "Inside every old person is a young person wondering what happened." So, what is aging? Aging is a manifestation of progressive, time-dependent failure of molecular mechanisms that create disorder within a system of DNA and its environment (nuclear, cytosolic, tissue, organ, organism, other organisms, society, terra firma, atmosphere, universe). Continuous signaling, transmitted with different kinetics across each of these environments, confers a "mutual enslavement" that creates ordered functions among the components within the system. Accrual of this molecular disorder overtime, i.e. during aging, causes progressive changes in the structure and function of the heart and arteries that are quite similar in humans, non-human primates, rabbits and rats that compromise cardiovascular reserve function, and confer a marked risk for incident cardiovascular disease. Nearly all aspects of signaling within the DNA environment system within the heart and arteries become disordered with advancing age: Signals change, as does sensing of the signals, transmission of signals and responses to signals, impaired cell renewal, changes in the proteome due to alterations in genomic transcription, mRNA translation, and proteostasis. The density of some molecules becomes reduced, and post-translational modifications, e.g. oxidation and nitration phosphorylation, lead to altered misfolding and disordered molecular interactions. The stoichiometry and kinetics of enzymatic and those reactions which underlie crucial cardiac and vascular cell functions and robust reserve mechanisms that remove damaged organelles and proteins deteriorate. The CV cells generate an inflammatory defense in an attempt to limit the molecular disorder. The resultant proinflammatory milieu is not executed by "professional" inflammatory cells (i.e. white blood cells), however, but by activation of renin-angiotensin-aldosterone endothelin signaling cascades that leads to endothelial and vascular smooth muscle and cardiac cells' phenotype shifts, resulting in production of inflammatory cytokines. Progressive molecular disorder within the heart and arteries over time leads to an excessive allostatic load on the CV system, that results in an increase and "overshoot" in the inflammatory defense signaling. This age-associated molecular disorder-induced inflammation that accrues in the heart and arteries does not, itself, cause clinical signs or symptoms of CVD. Clinical signs and symptoms of these CVDs begin to emerge, however, when the age-associated inflammation in the heart and arteries exceeds a threshold. Thus, an emerging school of thought is that accelerated age-associated alterations within the heart and arteries, per se, ought to be considered to be a type of CVD, because the molecular disorder and the inflammatory milieu it creates within the heart and arteries with advancing age are the roots of the pathophysiology of most cardiovascular diseases, e.g. athersclerosis and hypertension. Because many effects of aging on the CV system can be delayed or attenuated by changes in lifestyle, e.g. diet and exercise, or by presently available drugs, e.g. those that suppress Ang II signaling, CV aging is a promising frontier in preventive cardiology that is not only ripe for, but also in dire need of attention! There is an urgency to incorporate the concept of cardiovascular aging as a disease into clinical medicine. But, sadly, the reality of the age-associated molecular disorder within the heart and ateries has, for the most part, been kept outside of mainstream clinical medicine. This article is part of a Special Issue entitled CV Aging. Published by Elsevier Ltd. C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, Biomed Res Ctr,NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, Biomed Res Ctr,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov RI 刘, 李陆/H-8469-2015 FU Intramural Research Program of the NIH, National Institute on Aging FX The author would like to thank Ruth Sadler for editorial assistance and Harold Spurgeon and Jimmy Burril for work on figures. This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 69 TC 17 Z9 17 U1 6 U2 26 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 2015 VL 83 BP 1 EP 13 DI 10.1016/j.yjmcc.2015.04.005 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CL3GT UT WOS:000356839100001 PM 25870157 ER PT J AU Wang, MY Shah, AM AF Wang, Mingyi Shah, Ajay M. TI Age-associated pro-inflammatory remodeling and functional phenotype in the heart and large arteries SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Review DE Aging; Proinflammation; Cardiovascular remodeling; Ventricular-arterial coupling ID SMOOTH-MUSCLE-CELLS; NF-KAPPA-B; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CARDIAC-RESTRICTED OVEREXPRESSION; PRIMATE MACACA-MULATTA; NITRIC-OXIDE SYNTHASE; ANGIOTENSIN-II; OXIDATIVE-STRESS; ENDOTHELIAL DYSFUNCTION; MATRIX-METALLOPROTEINASE AB The aging population is increasing dramatically. Aging-associated stress simultaneously drives proinflammatory remodeling, involving angiotensin II and other factors, in both the heart and large arteries. The structural remodeling and functional changes that occur with aging include cardiac and vascular wall stiffening, systolic hypertension and suboptimal ventricular-arterial coupling, features that are often clinically silent and thus termed a silent syndrome. These age-related effects are the result of responses initiated by cardiovascular proinflammatory cells. Local proinflammatory signals are coupled between the heart and arteries due to common mechanical and humoral messengers within a closed circulating system. Thus, targeting proinflammatory signaling molecules would be a promising approach to improve age-associated suboptimal ventricular-arterial coupling, a major predisposing factor for the pathogenesis of clinical cardiovascular events such as heart failure. Published by Elsevier Ltd. C1 [Wang, Mingyi] NIA, Cardiovasc Sci Lab, NIH, BRC, Baltimore, MD 21224 USA. [Shah, Ajay M.] Kings Coll London, British Heart Fdn Ctr Excellence, Div Cardiovasc, London, England. RP Wang, MY (reprint author), NIA, Cardiovasc Sci Lab, NIH, BRC, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mingyiw@grc.nia.nih.gov; ajay.shah@kcl.ac.uk OI Shah, Ajay/0000-0002-6547-0631 FU British Heart Foundation; Foundation Leducq Transatlantic Network of Excellence Award; Department of Health via a National Institute for Health Research (NIHR) Biomedical Research Centre award; King's College London; King's College Hospital NHS Foundation Trust; National Institute on Aging, National Institutes of Health FX AMS is supported by the British Heart Foundation; a Foundation Leducq Transatlantic Network of Excellence Award; and the Department of Health via a National Institute for Health Research (NIHR) Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. MW is supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 156 TC 9 Z9 9 U1 0 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 2015 VL 83 BP 101 EP 111 DI 10.1016/j.yjmcc.2015.02.004 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CL3GT UT WOS:000356839100011 PM 25665458 ER PT J AU Greco, S Gorospe, M Martelli, F AF Greco, Simona Gorospe, Myriam Martelli, Fabio TI Noncoding RNA in age-related cardiovascular diseases SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Review DE MicroRNA; Long noncoding RNA; Aging; Cardiovascular disease ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; POSTTRANSCRIPTIONAL GENE-REGULATION; REGULATES CARDIAC-HYPERTROPHY; MODULATES TISSUE-RESPONSE; HEART-FAILURE PATIENTS; CIRCULATING MICRORNAS; OXIDATIVE STRESS; ENDOTHELIAL DYSFUNCTION; CALORIE RESTRICTION AB Eukaryotic gene expression is tightly regulated transcriptionally and post-transcriptionally by a host of noncoding (nc)RNAs. The best-studied class of short ncRNAs, microRNAs, mainly repress gene expression post-transcriptionally. Long noncoding (Inc)RNAs, which comprise RNAs differing widely in length and function, can regulate gene transcription as well as post-transcriptional mRNA fate. Collectively, ncRNAs affect a broad range of age-related physiologic deteriorations and pathologies, including reduced cardiovascular vigor and age-associated cardiovascular disease. This review presents an update of our understanding of regulatory ncRNAs contributing to cardiovascular health and disease as a function of advancing age. We will discuss (1) regulatory ncRNAs that control aging-associated cardiovascular homeostasis and disease, (2) the concepts, approaches, and methodologies needed to study regulatory ncRNAs in cardiovascular aging and (3) the challenges and opportunities that age-associated regulatory ncRNAs present in cardiovascular physiology and pathology. This article is part of a Special Issue entitled "CV Aging". (C) 2015 The Authors. Published by Elsevier Ltd. C1 [Greco, Simona; Martelli, Fabio] Policlin San Donato IRCCS, Mol Cardiol Lab, I-20097 Milan, Italy. [Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Martelli, F (reprint author), Policlin San Donato IRCCS, Mol Cardiol Lab, Via Morandi 30, I-20097 Milan, Italy. EM myriam-gorospe@nih.gov; fabio.martelli@grupposandonato.it RI greco, simona/J-5374-2016; OI greco, simona/0000-0002-0275-7221; Martelli, Fabio/0000-0002-8624-7738 FU Ministero della Salute; Fondazione Cariplo grant [2013-0887]; Telethon-Italy [GGP14092]; NIA-IRP, NIH [AG000393-07] FX This study was supported by Ministero della Salute (SG and FM), Fondazione Cariplo grant #2013-0887 (SG and FM) and Telethon-Italy GGP14092 (FM). KM Kim assisted with illustrations. MG was supported by the NIA-IRP, NIH (AG000393-07). NR 214 TC 27 Z9 31 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 2015 VL 83 BP 142 EP 155 DI 10.1016/j.yjmcc.2015.01.011 PG 14 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA CL3GT UT WOS:000356839100015 PM 25640162 ER PT J AU Genther, DJ Betz, J Pratt, S Martin, KR Harris, TB Satterfield, S Bauer, DC Newman, AB Simonsick, EM Lin, FR AF Genther, Dane J. Betz, Joshua Pratt, Sheila Martin, Kathryn R. Harris, Tamara B. Satterfield, Suzanne Bauer, Douglas C. Newman, Anne B. Simonsick, Eleanor M. Lin, Frank R. CA Hlth Aging Body Composition Study TI Association Between Hearing Impairment and Risk of Hospitalization in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hearing impairment; hospitalization; older adults; epidemiology ID QUICK DIAGNOSIS UNITS; ELDER LIFE PROGRAM; HEALTH-CARE USE; INCIDENT DEMENTIA; BODY-COMPOSITION; SOCIAL-ISOLATION; AGE; STATES; DISEASE; ADMISSION AB ObjectivesTo determine the association between hearing impairment (HI) and risk and duration of hospitalization in community-dwelling older adults in the United States. DesignProspective observational study. SettingHealth, Aging and Body Composition Study. ParticipantsWell-functioning community-dwelling white and black Medicare beneficiaries aged 70 to 79 at study enrollment in 1997-98 were followed for a median of 12years. MeasurementsIncidence, annual rate, and duration of hospitalization were the primary outcomes. Hearing was defined as the pure-tone average (PTA) of hearing thresholds in decibels re: hearing level (dB HL) at octave frequencies from 0.5 to 4.0kHz. Mild HI was defined as a PTA from 25 to 40dB HL, and moderate or greater HI was defined as a PTA greater than 40dB HL. ResultsOf the 2,148 participants included in the analysis, 1,801 (83.5%) experienced one or more hospitalizations, with 7,007 adjudicated hospitalization events occurring during the study period. Eight hundred eighty-two (41.1%) participants had normal hearing, 818 (38.1%) had mild HI, and 448 (20.9%) had moderate or greater HI. After adjusting for demographic characteristics and cardiovascular comorbidities, persons with mild HI experienced a 16% (hazard ratio (HR)=1.16, 95% confidence interval (CI) =1.04-1.29) greater risk of incident hospitalization and a 17% (incidence rate ratio (IRR)=1.17, 95% CI=1.04-1.32) greater annual rate of hospitalization, and those with moderate or greater HI experienced a 21% (HR=1.21, 95% CI=1.06-1.38) greater risk of incident hospitalization and a 19% (IRR=1.19, 95% CI=1.04-1.38) greater annual rate of hospitalization than persons with normal hearing. There was no significant association between HI and mean duration of hospitalization. ConclusionHearing-impaired older adults experience a greater incidence and annual rate of hospitalization than those with normal hearing. Investigating whether rehabilitative therapies could affect the risk of hospitalization in older adults requires further study. C1 [Genther, Dane J.; Lin, Frank R.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Genther, Dane J.; Betz, Joshua; Lin, Frank R.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD 21287 USA. [Betz, Joshua] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21287 USA. [Pratt, Sheila] Univ Pittsburgh, Geriatr Res Educ & Clin Ctr, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Pratt, Sheila] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [Martin, Kathryn R.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Martin, Kathryn R.] Univ Aberdeen, Sch Med & Dent, Epidemiol Grp, Aberdeen, Scotland. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Simonsick, Eleanor M.; Lin, Frank R.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. [Simonsick, Eleanor M.] Johns Hopkins Univ, NIA, Intramural Res Program, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. [Lin, Frank R.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. [Lin, Frank R.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. RP Genther, DJ (reprint author), Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,Suite 6210, Baltimore, MD 21287 USA. EM dgenthe2@jhmi.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Genther, Dane/0000-0002-7925-012X; Betz, Joshua/0000-0003-4488-9799 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050, K24AG031155]; National Institute of Nursing Research [R01-NR012459]; National Institutes of Health [T32DC000027]; National Institute on Deafness and Other Communication Disorders [K23DC011279]; Intramural Research Program of the NIA; Triological Society and American College of Surgeons through the Clinician Scientist Award; Eleanor Schwartz Charitable Foundation FX This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; NIA Grant R01-AG028050; and National Institute of Nursing Research Grant R01-NR012459. This study was further supported in part by National Institutes of Health Grant T32DC000027, NIA grant K24AG031155, National Institute on Deafness and Other Communication Disorders Grant K23DC011279, Intramural Research Program of the NIA, Triological Society and American College of Surgeons through the Clinician Scientist Award, and Eleanor Schwartz Charitable Foundation. Dr. Pratt was supported in part with resources and the use of facilities at the Department of Veterans Affairs Pittsburgh Healthcare System, although the contents do not represent the views of the Department of Veterans Affairs or the U.S. government. This work was presented as a poster display as part of the American Auditory Society Scientific and Technology Meeting, March 6-8, 2014, Scottsdale, Arizona. NR 42 TC 3 Z9 3 U1 2 U2 6 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 JUN PY 2015 VL 63 IS 6 BP 1146 EP 1152 DI 10.1111/jgs.13456 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CL1CG UT WOS:000356679500012 PM 26096388 ER PT J AU Tempero, M AF Tempero, Margaret TI Improving Access to Drugs-Big Pharma Comes to the Table SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Tempero, Margaret] UCSF Pancreas Ctr, San Francisco, CA 94143 USA. [Tempero, Margaret] NCI, Clin Oncol Study Sect CONC, Bethesda, MD 20892 USA. [Tempero, Margaret] NCI, Board Sci Counselors, Bethesda, MD 20892 USA. [Tempero, Margaret] Mayo Clin, External Advisory Boards Pancreas SPORES, Rochester, MN USA. [Tempero, Margaret] UAB Minnesota, Minneapolis, MN USA. [Tempero, Margaret] Univ Arizona, GI SPORE, Tucson, AZ 85721 USA. [Tempero, Margaret] V Fdn, Sci Advisory Boards Lustgarten Fdn, Pancreat Canc Act Network, Alberta Canada Canc Board, Edmonton, AB, Canada. [Tempero, Margaret] EORTC, Istanbul, Turkey. [Tempero, Margaret] UNMC, Eppley Canc Ctr, Omaha, NE USA. [Tempero, Margaret] UCFS, Div Med Oncol, Norwich, CT USA. [Tempero, Margaret] UCSF, Res Programs, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. RP Tempero, M (reprint author), UCSF Pancreas Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2015 VL 13 IS 6 BP 703 EP 703 PG 1 WC Oncology SC Oncology GA CL3IK UT WOS:000356843400001 PM 26085384 ER PT J AU Koo, OJ Ha, SK Park, SJ Park, HJ Kim, SJ Kwon, D Kang, JT Moon, JH Park, EJ Jang, G Lee, BC AF Koo, Ok Jae Ha, Seung-Kwon Park, Sol Ji Park, Hee Jung Kim, Su Jin Kwon, Daekee Kang, Jung Taek Moon, Joon Ho Park, Eun Jung Jang, Goo Lee, Byeong Chun TI Intrapancreatic ectopic splenic tissue found in a cloned miniature pig SO JOURNAL OF VETERINARY SCIENCE LA English DT Article DE cloned pig; intrapancreatic ectopic splenic tissue; somatic cell nuclear transfer ID ANIMALS AB Somatic cell nuclear transfer (SCNT) is a cost-effective technique for producing transgenic pigs. However, abnormalities in the cloned pigs might prevent use these animals for clinical applications or disease modeling. In the present study, we generated several cloned pigs. One of the pigs was found to have intrapancreatic ectopic splenic tissue during histopathology analysis although this animal was grossly normal and genetically identical to the other cloned pigs. Ectopic splenic tissue in the pancreas is very rare, especially in animals. To the best of our knowledge, this is the first such report for cloned pigs. C1 [Koo, Ok Jae; Park, Hee Jung] Samsung Biomed Res Inst, Lab Anim Res Ctr, Suwon 440746, South Korea. [Ha, Seung-Kwon] NIAAA, NIH, Bethesda, MD 20892 USA. [Park, Sol Ji; Kim, Su Jin; Kwon, Daekee; Kang, Jung Taek; Moon, Joon Ho; Park, Eun Jung; Jang, Goo; Lee, Byeong Chun] Seoul Natl Univ, Dept Theriogenol & Biotechnol, Coll Vet Med, Seoul 151742, South Korea. RP Lee, BC (reprint author), Seoul Natl Univ, Dept Theriogenol & Biotechnol, Coll Vet Med, Seoul 151742, South Korea. EM bclee@snu.ac.kr FU Cooperative Research Program for Agriculture Science and Technology Development, Rural Development Administration, Korea [PJ009802]; Ministry of Trade, Industry and Energy (MOTIE) [10048948]; Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) [311011-05-3-SB010]; Brain Korea 21 PLUS Program for Creative Veterinary Science Research; Research Institute for Veterinary Science FX This work was supported by the Cooperative Research Program for Agriculture Science and Technology Development (no. PJ009802), Rural Development Administration, Korea; Ministry of Trade, Industry and Energy (MOTIE; no. 10048948), Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET; no. 311011-05-3-SB010), the Brain Korea 21 PLUS Program for Creative Veterinary Science Research, and the Research Institute for Veterinary Science. We thank Dr. Jung Bin Lee for performing the microsatellite analysis, Kahee Cho for providing histopathologic analysis; Yoon-Sang Kwon, Ji-Ho Kim, and Hyunil Kim for animal management and sample collection; and Barry Bavister for English editing and providing comments. NR 8 TC 0 Z9 0 U1 0 U2 0 PU KOREAN SOC VETERINARY SCIENCE PI SEOUL PA SEOUL NATL UNIV, COLLEGE VETERINARY MEDICINE,, SEOUL, 151-742, SOUTH KOREA SN 1229-845X EI 1976-555X J9 J VET SCI JI J. Vet. Sci. PD JUN PY 2015 VL 16 IS 2 BP 241 EP 244 DI 10.4142/jvs.2015.16.2.241 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA CL4EO UT WOS:000356905600016 PM 25643801 ER PT J AU Leandro, GS Sykora, P Bohr, VA AF Leandro, Giovana S. Sykora, Peter Bohr, Vilhelm A. TI The impact of base excision DNA repair in age-related neurodegenerative diseases SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT 11th International Conference on Environmental Mutagens CY NOV 03-08, 2013 CL Foz do Iguassu, BRAZIL DE Aging; DNA repair; Oxidative damage; Oxidative stress; Neurodegeneration; Alzheimers disease ID STRAND BREAK REPAIR; MILD COGNITIVE IMPAIRMENT; INCREASED OXIDATIVE DAMAGE; DEPENDENT PROTEIN-KINASE; HUMAN DERMAL FIBROBLASTS; AGING RAT NEURONS; ALZHEIMERS-DISEASE; MITOCHONDRIAL-DNA; COCKAYNE-SYNDROME; POLYMERASE-BETA AB The aging process and several age-related neurodegenerative disorders have been linked to elevated levels of DNA damage induced by ROS and deficiency in DNA repair mechanisms. DNA damage induced by ROS is a byproduct of cellular respiration and accumulation of damage over time, is a fundamental aspect of a main theory of aging. Mitochondria have a pivotal role in generating cellular oxidative stress, and mitochondrial dysfunction has been associated with several diseases. DNA base excision repair is considered the major pathway for repair of oxidized bases in DNA both in the nuclei and in mitochondria, and in neurons this mechanism is particularly important because non-diving cells have limited backup DNA repair mechanisms. An association between elevated oxidative stress and a decrease in BER is strongly related to the aging process and has special relevance in age-related neurodegenerative diseases. Here, we review the role of DNA repair in aging, focusing on the implications of the DNA base excision repair pathways and how alterations in expression of these DNA repair proteins are related to the aging process and to age-related neurodegenerative diseases. (C) 2015 Elsevier B.V. All rights reserved. C1 [Leandro, Giovana S.; Sykora, Peter; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Intramural Res Program, Biomed Res Ctr, Baltimore, MD 21224 USA. [Leandro, Giovana S.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto, SP, Brazil. RP Sykora, P (reprint author), NIA, Lab Mol Gerontol, Intramural Res Program, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sykorap@mall.nih.gov; bohrv@grc.nia.nih.gov RI Leandro, Giovana/F-2374-2013 OI Leandro, Giovana/0000-0003-0063-3601 FU intramural program of the National Institute on Aging, National Institutes of Health, US; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP FX This work was supported by funds from the intramural program of the National Institute on Aging, National Institutes of Health, US. Giovana S Leandro was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP. NR 151 TC 3 Z9 3 U1 0 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 EI 1873-135X J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUN PY 2015 VL 776 SI SI BP 31 EP 39 DI 10.1016/j.mrfmmm.2014.12.011 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA CL1WP UT WOS:000356735900006 PM 26255938 ER PT J AU Cooch, NK Stalnaker, TA Wied, HM Bali-Chaudhary, S McDannald, MA Liu, TL Schoenbaum, G AF Cooch, Nisha K. Stalnaker, Thomas A. Wied, Heather M. Bali-Chaudhary, Sheena McDannald, Michael A. Liu, Tzu-Lan Schoenbaum, Geoffrey TI Orbitofrontal lesions eliminate signalling of biological significance in cue-responsive ventral striatal neurons SO NATURE COMMUNICATIONS LA English DT Article ID NUCLEUS-ACCUMBENS CORE; INSTRUMENTAL TRANSFER; CORTEX; AMYGDALA; ENCODE; ASSOCIATIONS; BEHAVIOR; STIMULUS; SHELL; RATS AB The ventral striatum has long been proposed as an integrator of biologically significant associative information to drive actions. Although inputs from the amygdala and hippocampus have been much studied, the role of prominent inputs from orbitofrontal cortex (OFC) are less well understood. Here, we recorded single-unit activity from ventral striatum core in rats with sham or ipsilateral neurotoxic lesions of lateral OFC, as they performed an odour-guided spatial choice task. Consistent with prior reports, we found that spiking activity recorded in sham rats during cue sampling was related to both reward magnitude and reward identity, with higher firing rates observed for cues that predicted more reward. Lesioned rats also showed differential activity to the cues, but this activity was unbiased towards larger rewards. These data support a role for OFC in shaping activity in the ventral striatum to represent the biological significance of associative information in the environment. C1 [Cooch, Nisha K.; Wied, Heather M.; McDannald, Michael A.; Liu, Tzu-Lan; Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Stalnaker, Thomas A.; Bali-Chaudhary, Sheena; Schoenbaum, Geoffrey] NIDA, Intramural Res Program, Cellular Neurobiol Res Branch, Behav Neurophysiol Res Sect, Baltimore, MD 21224 USA. [Schoenbaum, Geoffrey] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA. RP Stalnaker, TA (reprint author), NIDA, Intramural Res Program, Cellular Neurobiol Res Branch, Behav Neurophysiol Res Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM thomas.stalnaker@nih.gov; geoffrey.schoenbaum@nih.gov FU NIDA FX This work was supported by funding from NIDA. The opinions expressed in this article are the authors' own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services or the United States government. NR 39 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2015 VL 6 AR 7195 DI 10.1038/ncomms8195 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CL7QM UT WOS:000357166800001 PM 26006060 ER PT J AU McCree, R Giattas, MR Sahasrabuddhe, VV Jolly, PE Martin, EY Usdan, SL Kohler, C Lisovicz, N AF McCree, Renicha Giattas, Mary Rose Sahasrabuddhe, Vikrant V. Jolly, Pauline E. Martin, Emichelle Y. Usdan, Stuart Lawrence Kohler, Connie Lisovicz, Nedra TI Expanding Cervical Cancer Screening and Treatment in Tanzania: Stakeholders' Perceptions of Structural Influences on Scale-Up SO ONCOLOGIST LA English DT Article DE Cervical cancer; Health services research; Service delivery; Screening and treatment ID LOW-RESOURCE SETTINGS; MIDDLE-INCOME COUNTRIES; PREVENTION SERVICES; HUMAN-PAPILLOMAVIRUS; VISUAL INSPECTION; SOUTH-AFRICA; ACETIC-ACID; PROGRAMS; ZAMBIA; HIV AB Tanzania has the highest burden of cervical cancer in East Africa. This study aims to identify perceived barriers and facilitators that influence scale-up of regional and population-level cervical cancer screening and treatment programs in Tanzania. Convenience sampling was used to select participants for this qualitative study among 35 key informants. Twenty-eight stakeholders from public-sector health facilities, academia, government, and nongovernmental organizations completed in-depth interviews, and a seven-member municipal health management team participated in a focus group discussion. The investigation identified themes related to the infrastructure of health services for cervical cancer prevention, service delivery, political will, and sociocultural influences on screening and treatment. Decentralizing service delivery, improving access to screening and treatment, increasing the number of trained health workers, and garnering political will were perceived as key facilitators for enhancing and initiating screening and treatment services. In conclusion, participants perceived that system-level structural factors should be addressed to expand regional and population-level service delivery of screening and treatment. C1 [McCree, Renicha] Ctr Global Hlth, Rockville, MD USA. [McCree, Renicha; Sahasrabuddhe, Vikrant V.] NCI, Rockville, MD 20850 USA. [Giattas, Mary Rose] Jhpiego, Dar Es Salaam, Tanzania. [Sahasrabuddhe, Vikrant V.] Vanderbilt Univ, Dept Global Hlth, Nashville, TN 37235 USA. [Jolly, Pauline E.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Martin, Emichelle Y.; Lisovicz, Nedra] Univ Alabama Birmingham, Dept Prevent Med, Birmingham, AL USA. [Kohler, Connie] Univ Alabama Birmingham, Dept Hlth Behav, Birmingham, AL USA. [Usdan, Stuart Lawrence] Univ Alabama, Dept Human Sci, Tuscaloosa, AL USA. RP McCree, R (reprint author), NCI, Canc Prevent Program, 9609 Med Ctr Dr,Room 2W-160, Rockville, MD 20850 USA. EM renicha.mccree@nih.gov FU Rejoice and Hope Ministries International; University of Alabama at Birmingham Cancer Prevention and Control Training Program (R25 Grant) [CA47888] FX We thank Dr. Innocent Semali for his guidance and expertise during the planning of this study and Stanford Mwasongwe for his help with data collection and organization. We are grateful to Rejoice and Hope Ministries International for funding this study. Dr. McCree thanks the University of Alabama at Birmingham Cancer Prevention and Control Training Program (R25 Grant CA47888) for supporting this research as part of her dissertation fellowship. NR 33 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2015 VL 20 IS 6 BP 621 EP 626 DI 10.1634/theoncologist.2013-0305 PG 6 WC Oncology SC Oncology GA CL1EC UT WOS:000356684400012 PM 25926351 ER PT J AU Wang, BH He, MF Chao, A Engelgau, MM Saraiya, M Wang, LM Wang, LH AF Wang, Baohua He, Minfu Chao, Ann Engelgau, Michael M. Saraiya, Mona Wang, Limin Wang, Linhong TI Cervical Cancer Screening Among Adult Women in China, 2010 SO ONCOLOGIST LA English DT Article DE Cervical cancer; Papanicolaou test; Women; China; Epidemiology ID RANDOMIZED CONTROLLED-TRIAL; RURAL CHINA; HEALTH; PREVENTION; BEHAVIOR; INDIA; AGE AB Introduction. Cervical cancer is one of the most commonly diagnosed cancers among women in China. The World Health Organization ( WHO) recommends routine screening for cervical cancer, and the WHO Global Monitoring Framework suggests that every nation monitors cervical cancer screening. However, little information is available on cervical cancer screening behavior among women in China. Methods. We used data from the 2010 China Chronic Disease and Risk Factor Surveillance System that included 51,989 women aged 18 years and older. We report the proportion of women who reported ever having had a Papanicolaou ( Pap) test, stratified by sociodemographic characteristics and geographic region. Multivariable logistic regression modeling was performed to adjust for potential confounders. Results. Overall, 21% of 51,989 women reported having ever had a Pap test. The highest proportion was reported among women aged 30-39 years (30.1%, 95% confidence interval, 26.8%-33.4%). In all geographic regions, women in rural areas were consistently less likely than women in urban areas to report having had a Pap test. Among women who reported ever having a Pap test, 82% reported having the most recent test in the past 3 years. Factors associated with reporting ever having a test were being aged 30-49 years, higher education, being married, and having urban health insurance. Conclusion. Our results indicate that screening programs need to be strengthened along with a more intense focus on specific demographic groups. National cervical cancer screening guidelines and comprehensive implementation strategies are needed to make screening services available and accessible to all women. C1 [Wang, Baohua; He, Minfu; Wang, Limin; Wang, Linhong] Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommunicable Dis Control & Pr, Beijing, Peoples R China. [Chao, Ann] NCI, Ctr Global Hlth, Rockville, MD USA. [Engelgau, Michael M.] Ctr Dis Control & Prevent, Ctr Global Hlth, Atlanta, GA USA. [Saraiya, Mona] Ctr Dis Control & Prevent, Ctr Chron Dis Prevent & Hlth Promot, Div Canc Control & Prevent, Atlanta, GA USA. RP Wang, LH (reprint author), 27 Nanwei Rd, Beijing 100050, Peoples R China. EM linhong@chinawch.org.cn FU National Health and Family Planning Commission of the People's Republic of China FX This study was funded by the National Health and Family Planning Commission of the People's Republic of China. We thank all study participants for taking part in this study. We are grateful to all staff members of the provincial and local health administrative departments and the provincial and county Centers for Disease Control and Prevention and the more than 2,000 field interviewers for their support and hard work. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. NR 33 TC 6 Z9 9 U1 2 U2 5 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 JUN PY 2015 VL 20 IS 6 BP 627 EP 634 DI 10.1634/theoncologist.2014-0303 PG 8 WC Oncology SC Oncology GA CL1EC UT WOS:000356684400013 PM 25956407 ER PT J AU Katagiri, S Hayashi, T Yoshitake, K Sergeev, Y Akahori, M Furuno, M Nishino, J Ikeo, K Tsunoda, K Tsuneoka, H Iwata, T AF Katagiri, Satoshi Hayashi, Takaaki Yoshitake, Kazutoshi Sergeev, Yuri Akahori, Masakazu Furuno, Masaaki Nishino, Jo Ikeo, Kazuho Tsunoda, Kazushige Tsuneoka, Hiroshi Iwata, Takeshi TI Congenital Achromatopsia and Macular Atrophy Caused by a Novel Recessive PDE6C Mutation (p.E591K) SO OPHTHALMIC GENETICS LA English DT Article DE Achromatopsia; OPN1SW; PDE6C; RHO; whole-exome sequencing ID TOTAL COLOURBLINDNESS; PROGRESSIVE LOSS; ALPHA-SUBUNIT; GENETIC-BASIS; CONE; DISEASE; PHOSPHODIESTERASE; CHANNEL; MUTANT; MOUSE AB Purpose: We have previously reported clinical features of two siblings, a sister with complete achromatopsia (ACHM) and a brother with incomplete ACHM, in a consanguineous Japanese family. With the current study, we intended to identify a disease-causing mutation in the siblings and to investigate why the phenotypes of the siblings differed. Methods: We performed a comprehensive ophthalmic examination for each sibling and parent. Whole-exome and Sanger sequencing were performed on genomic DNA. Molecular modeling was analyzed in an in silica study. Results: The ophthalmic examination revealed severe macular atrophy in the older female sibling at 30 years of age and mild macular atrophy in the brother at 26 years of age. The genetic analysis identified a novel homozygous PDE6C mutation (p.E591K) as the disease-causing allele in the siblings. Each parent was heterozygous for the mutation. Molecular modeling showed that the mutation could cause a conformational change in the PDE6C protein and result in reduced phosphodiesterase activity. We also identified an OPN1SW mutation (p.G79R), which is associated with congenital tritan deficiencies, in the sister and the father but not in the brother. Conclusions: A novel homozygous PDE6C mutation was identified as the cause of ACHM. In addition, we identified an OPN1SW mutation in the sibling with complete ACHM, which might explain the difference in phenotype (complete versus incomplete ACHM) between the siblings. C1 [Katagiri, Satoshi; Akahori, Masakazu; Iwata, Takeshi] Natl Hosp Org, Tokyo Med Ctr, Natl Inst Sensory Organs, Div Mol & Cellular Biol, Tokyo, Japan. [Katagiri, Satoshi; Hayashi, Takaaki; Tsuneoka, Hiroshi] Jikei Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan. [Yoshitake, Kazutoshi; Nishino, Jo; Ikeo, Kazuho] Natl Inst Genet, Lab DNA Data Anal, Shizuoka, Japan. [Sergeev, Yuri] NEI, NIH, Bethesda, MD 20892 USA. [Furuno, Masaaki] RIKEN Ctr Life Sci Technol, Div Genom Technol, Life Sci Accelerator Technol Grp, Transcriptome Technol Team, Yokohama, Kanagawa, Japan. [Tsunoda, Kazushige] Natl Hosp Org, Tokyo Med Ctr, Natl Inst Sensory Organs, Lab Visual Physiol, Tokyo, Japan. RP Hayashi, T (reprint author), Jikei Univ, Sch Med, Dept Ophthalmol, Minato Ku, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan. EM taka@jikei.ac.jp OI Katagiri, Satoshi/0000-0001-7787-8194 NR 36 TC 1 Z9 1 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1381-6810 EI 1744-5094 J9 OPHTHALMIC GENET JI Ophthalmic Genet. PD JUN PY 2015 VL 36 IS 2 BP 137 EP 144 DI 10.3109/13816810.2014.991932 PG 8 WC Genetics & Heredity; Ophthalmology SC Genetics & Heredity; Ophthalmology GA CK9FG UT WOS:000356545400007 PM 25605338 ER PT J AU Mensah, GA Engelgau, M Stoney, C Mishoe, H Kaufmann, P Freemer, M Fine, L AF Mensah, George A. Engelgau, Michael Stoney, Catherine Mishoe, Helena Kaufmann, Peter Freemer, Michelle Fine, Lawrence CA Trans-NHLBI T4 Translation Res Wor TI News from NIH: a center for translation research and implementation science SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT News Item DE Translation research; Implementation science; Population health impact; Prevention; Behavior change; Systems science; NIH funding opportunity ID CARDIOVASCULAR-DISEASE; DISPARITIES C1 [Mensah, George A.; Engelgau, Michael; Stoney, Catherine; Mishoe, Helena; Kaufmann, Peter; Freemer, Michelle; Fine, Lawrence; Trans-NHLBI T4 Translation Res Wor] NHLBI, Ctr Translat Res & Implementat Sci CTRIS, NIH, Rockledge Ctr 1, Bethesda, MD 20892 USA. RP Mensah, GA (reprint author), NHLBI, Ctr Translat Res & Implementat Sci CTRIS, NIH, Rockledge Ctr 1, 6705 Rockledge Dr,Suite 6070, Bethesda, MD 20892 USA. EM George.Mensah@nih.gov NR 14 TC 5 Z9 5 U1 2 U2 3 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1869-6716 EI 1613-9860 J9 TRANSL BEHAV MED JI Transl. Behav. Med. PD JUN PY 2015 VL 5 IS 2 BP 127 EP 130 DI 10.1007/s13142-015-0310-7 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL2QI UT WOS:000356788700001 PM 26029274 ER PT J AU Volkow, ND Baler, RD AF Volkow, Nora D. Baler, Ruben D. TI NOW vs LATER brain circuits: implications for obesity and addiction SO TRENDS IN NEUROSCIENCES LA English DT Review DE delay discounting; striatum; dopamine; intertemporal trade-off ID NUCLEUS-ACCUMBENS DOPAMINE; CHILDHOOD SELF-CONTROL; DECISION-MAKING; ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; IMPULSIVE CHOICE; PATHOLOGICAL GAMBLERS; NEURAL MECHANISMS; CONDUCT DISORDER; CONSTRUAL-LEVEL AB Balancing behaviors that provide a reward NOW versus behaviors that provide an advantage LATER is critical for survival. We propose a model in which dopamine (DA) can favor NOW processes through phasic signaling in reward circuits or LATER processes through tonic signaling in control circuits. At the same time, through its modulation of the orbitofrontal cortex, which processes salience attribution, DA also enables shifting from NOW to LATER, while its modulation of the insula, which processes interoceptive information, influences the probability of selecting NOW vs LATER actions on the basis of an individual's physiological state. Disruptions along these circuits contribute to diverse pathologies, including obesity and addiction. C1 [Volkow, Nora D.; Baler, Ruben D.] NIDA, NIH, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 131 TC 18 Z9 18 U1 3 U2 31 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUN PY 2015 VL 38 IS 6 BP 345 EP 352 DI 10.1016/j.tins.2015.04.002 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CL5FM UT WOS:000356985200004 PM 25959611 ER PT J AU Marcum, CS Koehly, LM AF Marcum, Christopher Steven Koehly, Laura M. TI Inter-generational contact from a network perspective SO ADVANCES IN LIFE COURSE RESEARCH LA English DT Article DE Networks; Generations; Family communication ID SOCIAL NETWORKS; UNITED-STATES; IMMIGRANT FAMILIES; AGE; SIMULATION; GENERATION; SOCIOLOGY; MIGRATION; PATTERNS; CHILDREN AB Pathways for resource - or other - exchanges within families have long been known to be dependent on the structure of relations between generations (Agree et al., 2005; Fuller-Thomson et al., 1997; Silverstein, 2011; Treas & Marcum, 2011). Much life course research has theorized models of inter-generational exchange - including, the 'sandwich generation' (Miller, 1981) and the 'skipped generation' pathways (Chalfie, 1994) - but there is little work relating these theories to relevant network mechanisms such as liaison brokerage (Gould & Fernandez, 1989) and other triadic configurations (Davis & Leinhardt, 1972; Wasserman & Faust, 1994). To address this, a survey of models of resource allocation between members of inter-generational households from a network perspective is introduced in this paper. Exemplary data come from health discussion networks among Mexican-origin multi-generational households. Published by Elsevier Ltd. C1 [Marcum, Christopher Steven; Koehly, Laura M.] NIH, Bethesda, MD 20892 USA. RP Marcum, CS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM chris.marcum@nih.gov OI Marcum, Christopher/0000-0002-0899-6143 FU National Institutes of Health Intramural Research Program [Z01HG200335] FX We would like to thank the anonymous reviewers and Dr. Judith Treas, who offered useful feedback on drafts of this manuscript. This research is funded by the National Institutes of Health Intramural Research Program (grant number Z01HG200335 to L.M.K.). NR 70 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1569-4909 EI 1879-6974 J9 ADV LIFE COURSE RES JI Adv. Life Course Res. PD JUN PY 2015 VL 24 BP 10 EP 20 DI 10.1016/j.alcr.2015.04.001 PG 11 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA CL2CB UT WOS:000356750100002 PM 26047986 ER PT J AU Fahrmann, J Grapov, D Yang, J Hammock, B Fiehn, O Bell, GI Hara, M AF Fahrmann, Johannes Grapov, Dmitry Yang, Jun Hammock, Bruce Fiehn, Oliver Bell, Graeme I. Hara, Manami TI Systemic alterations in the metabolome of diabetic NOD mice delineate increased oxidative stress accompanied by reduced inflammation and hypertriglyceremia SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE diabetic mice; metabolomics; inflammation; oxidative stress ID BETA-CELL FUNCTION; INSULIN-SECRETION; ISLET AUTOIMMUNITY; HOMOCYSTEINE METABOLISM; MASS-SPECTROMETRY; ARACHIDONIC-ACID; AMINO-ACID; GLUCOSE; MELLITUS; IDENTIFICATION AB 1 diabetes (T1D). However, not all animals will develop overt diabetes despite undergoing similar autoimmune insult. In this study, a comprehensive metabolomic approach, consisting of gas chromatography time-of-flight (GC-TOF) mass spectrometry (MS), ultra-high-performance liquid chromatography-accurate mass quadruple time-of-flight (UHPLC-qTOF) MS and targeted UHPLC-tandem mass spectrometry-based methodologies, was used to capture metabolic alterations in the metabolome and lipidome of plasma from NOD mice progressing or not progressing to T1D. Using this multi-platform approach, we identified >1,000 circulating lipids and metabolites in male and female progressor and nonprogressor animals (n = 71). Statistical and multivariate analyses were used to identify age-and sex-independent metabolic markers, which best differentiated metabolic profiles of progressors and nonprogressors. Key T1D-associated perturbations were related with 1) increases in oxidation products glucono-delta-lactone and galactonic acid and reductions in cysteine, methionine and threonic acid, suggesting increased oxidative stress; 2) reductions in circulating polyunsaturated fatty acids and lipid signaling mediators, most notably arachidonic acid (AA) and AA-derived eicosanoids, implying impaired states of systemic inflammation; 3) elevations in circulating triacylglyercides reflective of hypertriglyceridemia; and 4) reductions in major structural lipids, most notably lysophosphatidylcholines and phosphatidylcholines. Taken together, our results highlight the systemic perturbations that accompany a loss of glycemic control and development of overt T1D. C1 [Fahrmann, Johannes; Grapov, Dmitry; Fiehn, Oliver] Univ Calif Davis, NIH, West Coast Metabol Ctr, Davis, CA 95616 USA. [Yang, Jun; Hammock, Bruce] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Yang, Jun; Hammock, Bruce] Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA. [Bell, Graeme I.; Hara, Manami] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Hara, M (reprint author), Univ Chicago, Dept Med, 5841 South Maryland Ave,MC1027, Chicago, IL 60637 USA. EM mhara@midway.uchicago.edu FU National Institutes of Health [U24 DK-097154]; NIEHS [R01 ES-002710, P42 ES-004699] FX This research is funded by the National Institutes of Health Grant U24 DK-097154, and is partially supported by NIEHS R01 ES-002710 and P42 ES-004699. NR 60 TC 6 Z9 6 U1 2 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN 1 PY 2015 VL 308 IS 11 BP E978 EP E989 DI 10.1152/ajpendo.00019.2015 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA CK5ID UT WOS:000356256100006 PM 25852003 ER PT J AU Hays, AG Iantorno, M Soleimanifard, S Steinberg, A Schar, M Gerstenblith, G Stuber, M Weiss, RG AF Hays, Allison G. Iantorno, Micaela Soleimanifard, Sahar Steinberg, Angela Schaer, Michael Gerstenblith, Gary Stuber, Matthias Weiss, Robert G. TI Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE endothelial function; coronary artery disease; magnetic resonance imaging ID MAGNETIC-RESONANCE ANGIOGRAPHY; ARTERY-DISEASE; BLOOD-FLOW; HEALTHY-SUBJECTS; BREATH-HOLD; DYSFUNCTION; HUMANS; VASODILATION; VELOCITY; INFLAMMATION AB Endothelial cell release of nitric oxide (NO) is a defining characteristic of nondiseased arteries, and abnormal endothelial NO release is both a marker of early atherosclerosis and a predictor of its progression and future events. Healthy coronaries respond to endothelial-dependent stressors with vasodilatation and increased coronary blood flow (CBF), but those with endothelial dysfunction respond with paradoxical vasoconstriction and reduced CBF. Recently, coronary MRI and isometric handgrip exercise (IHE) were reported to noninvasively quantify coronary endothelial function (CEF). However, it is not known whether the coronary response to IHE is actually mediated by NO and/or whether it is reproducible over weeks. To determine the contribution of NO, we studied the coronary response to IHE before and during infusion of N-G-monomethyl-L-arginine (L-NMMA, 0.3 mg.kg(-1).min(-1)), a NO-synthase inhibitor, in healthy volunteers. For reproducibility, we performed two MRI-IHE studies similar to 8 wk apart in healthy subjects and patients with coronary artery disease (CAD). Changes from rest to IHE in coronary cross-sectional area (%CSA) and diastolic CBF (%CBF) were quantified. L-NMMA completely blocked normal coronary vasodilation during IHE [%CSA, 12.9 +/- 2.5 (mean +/- SE, placebo) vs. -0.3 +/- 1.6% (L-NMMA); P < 0.001] and significantly blunted the increase in flow [%CBF, 47.7 +/- 6.4 (placebo) vs. 10.6 +/- 4.6% (L-NMMA); P < 0.001]. MRI-IHE measures obtained weeks apart strongly correlated for CSA (P < 0.0001) and CBF (P < 0.01). In conclusion, the normal human coronary vasoactive response to IHE is primarily mediated by NO. This noninvasive, reproducible MRI-IHE exam of NO-mediated CEF promises to be useful for studying CAD pathogenesis in low-risk populations and for evaluating translational strategies designed to alter CAD in patients. C1 [Hays, Allison G.; Iantorno, Micaela; Steinberg, Angela; Gerstenblith, Gary; Weiss, Robert G.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. [Iantorno, Micaela] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Soleimanifard, Sahar; Schaer, Michael; Stuber, Matthias; Weiss, Robert G.] Johns Hopkins Univ, Dept Radiol, Div Magnet Resonance Res, Baltimore, MD USA. [Soleimanifard, Sahar] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Stuber, Matthias] CHU Vaudois, Dept Radiol, Ctr Biomed Imaging, CH-1011 Lausanne, Switzerland. [Stuber, Matthias] Univ Lausanne, Lausanne, Switzerland. RP Weiss, RG (reprint author), Johns Hopkins Univ Hosp, Blalock 544,600 N Wolfe St, Baltimore, MD 21287 USA. EM rweiss@jhmi.edu RI Schar, Michael/C-8087-2015; OI Schar, Michael/0000-0002-7044-9941; Stuber, Matthias/0000-0001-9843-2028 FU National Heart, Lung, and Blood Institute [HL120905, HL125059]; American Heart Association [11SDG5200004]; Clarence Doodeman Endowment of Johns Hopkins FX This work was supported by National Heart, Lung, and Blood Institute Grants HL120905 and HL125059, American Heart Association Grant 11SDG5200004, and the Clarence Doodeman Endowment of Johns Hopkins. NR 36 TC 2 Z9 2 U1 0 U2 2 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 JUN 1 PY 2015 VL 308 IS 11 BP H1343 EP H1350 DI 10.1152/ajpheart.00023.2015 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA CK5MS UT WOS:000356269600005 PM 25820391 ER PT J AU Meterko, M Marfeo, EE McDonough, CM Jette, AM Ni, PS Bogusz, K Rasch, EK Brandt, DE Chan, L AF Meterko, Mark Marfeo, Elizabeth E. McDonough, Christine M. Jette, Alan M. Ni, Pengsheng Bogusz, Kara Rasch, Elizabeth K. Brandt, Diane E. Chan, Leighton TI Work Disability Functional Assessment Battery: Feasibility and Psychometric Properties SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Disability evaluation; Outcomes assessment (health care); Psychometrics; Rehabilitation; United States Social Security Administration; Validation studies ID BEHAVIORAL HEALTH FUNCTION; QUALITY-OF-LIFE; PHYSICAL FUNCTION INSTRUMENT; ITEM POOL CONSTRUCTION; SELF-REPORT; APPROPRIATENESS MEASUREMENT; VALIDITY; RELIABILITY; DISEASE; PAIN AB Objective: To assess the feasibility and psychometric properties of 8 scales covering 2 domains of the newly developed Work Disability Functional Assessment Battery (WD-FAB): physical function (PF) and behavioral health (BH) function. Design: Cross-sectional study. Setting: Community. Participants: Adults (N=973) unable to work because of a physical (n=497) or a mental (n=476) disability. Interventions: Not applicable. Main Outcome Measures: Each disability group responded to a survey consisting of the relevant WD-FAB scales and existing measures of established validity. The WD-FAB scales were evaluated with regard to data quality (score distribution, percentage of "I don't know" responses), efficiency of administration (number of items required to achieve reliability criterion, time required to complete the scale) by computerized adaptive testing (CAT), and measurement accuracy as tested by person fit. Construct validity was assessed by examining both convergent and discriminant correlations between the WD-FAB scales and scores on same-domain and cross-domain established measures. Results: Data quality was good, and CAT efficiency was high across both WD-FAB domains. Measurement accuracy was very good for PP scales; BH scales demonstrated more variability. Construct validity correlations, both convergent and divergent, between all WD-FAB scales and established measures were in the expected direction and range of magnitude. Conclusions: The data quality, CAT efficiency, person fit, and construct validity of the WD-FAB scales were well supported and suggest that the WD-FAB could be used to assess PP and BH function related to work disability. Variation in scale performance suggests the need for future work on item replenishment and refinement, particularly with regard to the Self-Efficacy scale. (C) 2015 by the American Congress of Rehabilitation Medicine C1 [Meterko, Mark; Marfeo, Elizabeth E.; McDonough, Christine M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara] Boston Univ, Hlth & Disabil Res Inst, Sch Publ Hlth, Boston, MA 02118 USA. [Meterko, Mark] Ctr Healthcare Org & Implementat Res, VA Boston Healthcare Syst, Boston, MA USA. [Rasch, Elizabeth K.; Brandt, Diane E.; Chan, Leighton] Mark O Hatfield Clin Res Ctr, NIH, Rehabil Med Dept, Bethesda, MD 20892 USA. RP Meterko, M (reprint author), Boston Univ, Hlth & Disabil Res Inst, Sch Publ Hlth, 715 Albany St T5W, Boston, MA 02118 USA. EM Meterkom@bu.edu FU Social Security Administration-National Institutes of Health Interagency Agreements under the National Institutes of Health [HHSN269200900004C, HHSN269201000011C, HHSN2692011000091]; National Institutes of Health Intramural Research Program FX Supported by Social Security Administration-National Institutes of Health Interagency Agreements under the National Institutes of Health (contract nos. HHSN269200900004C, HHSN269201000011C, and HHSN2692011000091) and by the National Institutes of Health Intramural Research Program. NR 26 TC 2 Z9 2 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2015 VL 96 IS 6 BP 1028 EP 1035 DI 10.1016/j.apmr.2014.11.025 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CK7FM UT WOS:000356398200009 PM 25528263 ER PT J AU Musich, T Demberg, T Morgan, IL Estes, JD Franchini, G Robert-Guroff, M AF Musich, Thomas Demberg, Thorsten Morgan, Ian L. Estes, Jacob D. Franchini, Genoveffa Robert-Guroff, Marjorie TI Purification and functional characterization of mucosal IgA from vaccinated and SIV-infected rhesus macaques SO CLINICAL IMMUNOLOGY LA English DT Article DE Non-human primate mucosal IgA; Feces; Peptide M; Neutralization; Phagocytosis; Transcytosis inhibition ID IMMUNE-RESPONSES; SECRETORY IGA; IMMUNOGLOBULIN-A; HIV-1 INFECTION; FECAL EXTRACTS; ANTIBODIES; FC; BINDING; IMMUNIZATION; CHALLENGE AB Vaccine-induced mucosal antibodies are often evaluated using small volumes of secretory fluids. However, fecal matter containing mucosal IgA is abundant. We purified fecal IgA from five SIV-vaccinated and five SIV-infected rhesus macaques by sequential affinity chromatography. The purified IgA was dimeric by native PAGE, contained secretory component, and was analogous to IgA in colostrum and vaginal fluid by western blot. IgA from one infected and four vaccinated animals neutralized H9-derived SIV(mac)251 with IC(50)s as low as 1 mu g/mL. Purified IgAs inhibited transcytosis and exhibited phagocytic activity, the latter significantly correlated with SIV(mac)251 Env-specific IgA in the purified samples. Among different affinity resins, peptide M was optimal compared to jacalin, anti-monkey IgA and SSL7 for IgA purification, as confirmed using tandem peptide M/anti-monkey IgA columns. Fecal IgA provided material sufficient for several assays relevant to protective efficacy, and was shown to be multifunctional. Our approach is potentially applicable to human clinical studies. Published by Elsevier Inc. C1 [Musich, Thomas; Demberg, Thorsten; Morgan, Ian L.; Franchini, Genoveffa; Robert-Guroff, Marjorie] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Estes, Jacob D.] Frederick Natl Lab Canc Res, Frederick, MD USA. RP Robert-Guroff, M (reprint author), NCI, Vaccine Branch, CCR, NIH, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN26100800001E]; Intramural Research Program of the National Institutes of Health, National Cancer Institute FX We gratefully acknowledge the animal caretakers at ABL and the NIH Animal Center for their excellent care of the animals and collection of samples. Rhesus IgA and IgG standards were obtained through the NIH Nonhuman Primate Reagent Resource. This work was supported in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract No. HHSN26100800001E, and in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. The content of this publication,does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 55 TC 2 Z9 2 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 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2015 VL 158 IS 2 BP 127 EP 139 DI 10.1016/j.clim.2015.03.020 PG 13 WC Immunology SC Immunology GA CK7FJ UT WOS:000356397900001 PM 25840105 ER PT J AU Shepperd, JA Waters, EA Weinstein, ND Klein, WMP AF Shepperd, James A. Waters, Erika A. Weinstein, Neil D. Klein, William M. P. TI A Primer on Unrealistic Optimism SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE LA English DT Article DE unrealistic optimism; comparative optimism; optimistic bias; risk judgments; risk perception ID PERSONAL RISK; HEART-DISEASE; SELF; BIAS; BEHAVIOR; EVENT; MODERATORS; POSITIVITY; PREDICTION; KNOWLEDGE AB People display unrealistic optimism in their predictions about countless events, believing that their personal future outcomes will be more desirable than can possibly be true. We summarize the vast literature on unrealistic optimism by focusing on four broad questions: What is unrealistic optimism, when does it occur, why does it occur, and what are its consequences? Unrealistic optimism can be operationalized in multiple ways; is commonplace yet has well-established boundary conditions; occurs for a variety of reasons; and has consequences for affect, decision making, and behavior. C1 [Shepperd, James A.] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [Waters, Erika A.] Washington Univ, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63130 USA. [Weinstein, Neil D.] Rutgers State Univ, Dept Human Ecol, Piscataway, NJ 08855 USA. [Klein, William M. P.] NCI, Bethesda, MD 20892 USA. RP Shepperd, JA (reprint author), Univ Florida, Dept Psychol, POB 112250, Gainesville, FL 32611 USA. EM shepperd@ufl.edu OI Waters, Erika/0000-0001-7402-0133 FU Intramural NIH HHS [Z99 CA999999]; NIDCR NIH HHS [U54 DE019261]; NIMHD NIH HHS [L60 MD006280] NR 40 TC 15 Z9 15 U1 3 U2 33 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0963-7214 EI 1467-8721 J9 CURR DIR PSYCHOL SCI JI Curr. Dir. Psychol. PD JUN PY 2015 VL 24 IS 3 BP 232 EP 237 DI 10.1177/0963721414568341 PG 6 WC Psychology, Multidisciplinary SC Psychology GA CK6AH UT WOS:000356309600012 PM 26089606 ER PT J AU Yin, LL Maddison, LA Li, MY Kara, N LaFave, MC Varshney, GK Burgess, SM Patton, JG Chen, WB AF Yin, Linlin Maddison, Lisette A. Li, Mingyu Kara, Nergis LaFave, Matthew C. Varshney, Gaurav K. Burgess, Shawn M. Patton, James G. Chen, Wenbiao TI Multiplex Conditional Mutagenesis Using Transgenic Expression of Cas9 and sgRNAs SO GENETICS LA English DT Article DE CRISPR/Cas9; conditional mutagenesis; glucose homeostasis; retinal regeneration; zebrafish ID GENE-EXPRESSION; GENOME-WIDE; BETA-CELLS; ZEBRAFISH; SYSTEM; DROSOPHILA; MICE; REGENERATION; CRISPR-CAS9; KNOCKOUT AB Determining the mechanism of gene function is greatly enhanced using conditional mutagenesis. However, generating engineered conditional alleles is inefficient and has only been widely used in mice. Importantly, multiplex conditional mutagenesis requires extensive breeding. Here we demonstrate a system for one-generation multiplex conditional mutagenesis in zebrafish (Danio rerio) using transgenic expression of both cas9 and multiple single guide RNAs (sgRNAs). We describe five distinct zebrafish U6 promoters for sgRNA expression and demonstrate efficient multiplex biallelic inactivation of tyrosinase and insulin receptor a and b, resulting in defects in pigmentation and glucose homeostasis. Furthermore, we demonstrate temporal and tissue-specific mutagenesis using transgenic expression of Cas9. Heat-shock-inducible expression of cas9 allows temporal control of tyr mutagenesis. Liver-specific expression of cas9 disrupts insulin receptor a and b, causing fasting hypoglycemia and postprandial hyperglycemia. We also show that delivery of sgRNAs targeting ascl1a into the eye leads to impaired damage-induced photoreceptor regeneration. Our findings suggest that CRISPR/Cas9-based conditional mutagenesis in zebrafish is not only feasible but rapid and straightforward. C1 [Yin, Linlin; Maddison, Lisette A.; Li, Mingyu; Chen, Wenbiao] Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA. [Kara, Nergis; Patton, James G.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37240 USA. [LaFave, Matthew C.; Varshney, Gaurav K.; Burgess, Shawn M.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA. RP Chen, WB (reprint author), 702 Light Hall,2215 Garland Ave, Nashville, TN 37232 USA. EM wenbiao.chen@vanderbilt.edu OI LaFave, Matthew/0000-0001-9165-041X; Varshney, Gaurav K./0000-0002-0429-1904 FU Vanderbilt Diabetes Research and Training Center; NIH [DK088686, R01 EY024354]; American Diabetes Association [1-13-BS-027] FX We thank Amanda Goodrich and Corey Guthrie of the Vanderbilt University Medical Center Zebrafish Facility for expert care of zebrafish; and Baishali Maskeri, Alice Young, and Robert Blakesley of National Institutes of Health Intramural Sequencing Center for providing sequencing data. This work was supported by the Vanderbilt Diabetes Research and Training Center, the NIH (DK088686 to W.C., R01 EY024354 to J.G.P., and intramural research grants to S.M.B.), and the American Diabetes Association (1-13-BS-027 to W.C.). NR 56 TC 24 Z9 26 U1 4 U2 27 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD JUN PY 2015 VL 200 IS 2 BP 431 EP + DI 10.1534/genetics.115.176917 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA CK8SR UT WOS:000356509100005 PM 25855067 ER PT J AU Marques, AR AF Marques, Adriana R. TI Laboratory Diagnosis of Lyme Disease Advances and Challenges SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Lyme disease; Borrelia burgdorferi; Laboratory diagnosis; Serology ID ACRODERMATITIS CHRONICA ATROPHICANS; LINKED-IMMUNOSORBENT-ASSAY; CONFIRMED ERYTHEMA MIGRANS; BURGDORFERI SENSU-STRICTO; BORRELIA-BURGDORFERI; CEREBROSPINAL-FLUID; UNITED-STATES; ANTIBIOTIC-TREATMENT; CLINICAL SPECTRUM; ANTIBODY-RESPONSE AB The majority of laboratory tests performed for the diagnosis of Lyme disease are based on detection of the antibody responses against B burgdorferi in serum. The sensitivity of antibody-based tests increases with the duration of the infection. Patients early in their illness are more likely to have a negative result. There is a need to simplify the testing algorithm for Lyme disease, improving sensitivity in early disease while still maintaining high specificity and providing information about the stage of infection. The development of a point of care assay and biomarkers for active infection would be major advances for the field. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Marques, AR (reprint author), NIAID, Lab Clin Infect Dis, NIH, 10-12C118 10 Ctr Dr, Bethesda, MD 20892 USA. EM amarques@niaid.nih.gov FU Intramural Research Program National Institute of Allergy and Infectious Diseases, NIH FX This research was supported by the Intramural Research Program National Institute of Allergy and Infectious Diseases, NIH. NR 100 TC 10 Z9 11 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 EI 1557-9824 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 2015 VL 29 IS 2 BP 295 EP + DI 10.1016/j.idc.2015.02.005 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CL0LT UT WOS:000356634900008 PM 25999225 ER PT J AU Johnson, TP Shariff-Marco, S Willis, G Cho, YI Breen, N Gee, GC Krieger, N Grant, D Alegria, M Mays, VM Williams, DR Landrine, H Liu, B Reeve, BB Takeuchi, D Ponce, NA AF Johnson, Timothy P. Shariff-Marco, Salma Willis, Gordon Cho, Young Ik Breen, Nancy Gee, Gilbert C. Krieger, Nancy Grant, David Alegria, Margarita Mays, Vickie M. Williams, David R. Landrine, Hope Liu, Benmei Reeve, Bryce B. Takeuchi, David Ponce, Ninez A. TI Sources of Interactional Problems in a Survey of Racial/Ethnic Discrimination SO INTERNATIONAL JOURNAL OF PUBLIC OPINION RESEARCH LA English DT Article ID HEALTH SURVEYS; RESPONDENT; COMPREHENSION; QUESTION AB Cross-cultural variability in respondent processing of survey questions may bias results from multiethnic samples. We analyzed behavior codes, which identify difficulties in the interactions of respondents and interviewers, from a discrimination module contained within a field test of the 2007 California Health Interview Survey. In all, 553 (English) telephone interviews yielded 13,999 interactions involving 22 items. Multilevel logistic regression modeling revealed that respondent age and several item characteristics (response format, customized questions, length, and first item with new response format), but not race/ethnicity, were associated with interactional problems. These findings suggest that item function within a multi-cultural, albeit English language, survey may be largely influenced by question features, as opposed to respondent characteristics such as race/ethnicity. C1 [Johnson, Timothy P.] Univ Illinois, Survey Res Lab, Chicago, IL 60607 USA. [Shariff-Marco, Salma] Canc Prevent Inst Calif, Fremont, CA USA. [Shariff-Marco, Salma] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Rockville, MD USA. [Liu, Benmei] Stanford Univ, Sch Med, Rockville, MD USA. [Willis, Gordon] NCI, Div Canc Control & Populat Sci, Appl Res Program, Rockville, MD USA. [Breen, Nancy] NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Rockville, MD USA. [Cho, Young Ik] Univ Wisconsin, Milwaukee, WI 53201 USA. [Gee, Gilbert C.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA. [Grant, David; Ponce, Ninez A.] Univ Calif Los Angeles, Calif Hlth Interview Survey, Ctr Hlth Policy & Res, Los Angeles, CA USA. [Ponce, Ninez A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Krieger, Nancy; Grant, David] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Alegria, Margarita] Ctr Multicultural Mental Hlth Res, Somerville, MA USA. [Mays, Vickie M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Landrine, Hope] E Carolina Univ, Ctr Hlth Dispar Res, Greenville, NC USA. [Reeve, Bryce B.] Univ N Carolina, Gillings Sch Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Takeuchi, David] Boston Coll, Grad Sch Social Work, Chestnut Hill, MA 02167 USA. RP Johnson, TP (reprint author), Univ Illinois, Survey Res Lab, MC 336,629 CUPPA Hall,412 S Peoria, Chicago, IL 60607 USA. EM timj@uic.edu OI Ponce, Ninez/0000-0001-5151-6718 FU NIMHD NIH HHS [P60 MD006923] NR 20 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0954-2892 EI 1471-6909 J9 INT J PUBLIC OPIN R JI Int. J. Public Opin. Res. PD SUM PY 2015 VL 27 IS 2 BP 244 EP 263 DI 10.1093/ijpor/edu024 PG 20 WC Communication SC Communication GA CK5BF UT WOS:000356236400005 PM 26166949 ER PT J AU Arai, AE AF Arai, Andrew E. TI Healing After Myocardial Infarction A Loosely Defined Process SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE acute MI; microvascular obstruction; T2-weighted MRI ID CARDIOVASCULAR MAGNETIC-RESONANCE; EDEMA; AREA; RISK C1 NHLBI, Adv Cardiovasc Imaging, NIH, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Adv Cardiovasc Imaging, NIH, Bldg 10,Room B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM araia@nih.gov FU Intramural NIH HHS; PHS HHS [ZIAHL006136] NR 11 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JUN PY 2015 VL 8 IS 6 BP 680 EP 683 DI 10.1016/j.jcmg.2015.02.012 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CK9LC UT WOS:000356560600008 PM 26068285 ER PT J AU Arem, H Moore, SC Patel, A Hartge, P de Gonzalez, AB Visvanathan, K Campbell, PT Freedman, M Weiderpass, E Adami, HO Linet, MS Lee, IM Matthews, CE AF Arem, Hannah Moore, Steven C. Patel, Alpa Hartge, Patricia de Gonzalez, Amy Berrington Visvanathan, Kala Campbell, Peter T. Freedman, Michal Weiderpass, Elisabete Adami, Hans Olov Linet, Martha S. Lee, I. -Min Matthews, Charles E. TI Leisure Time Physical Activity and Mortality A Detailed Pooled Analysis of the Dose-Response Relationship SO JAMA INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; VIGOROUS EXERCISE; BREAST-CANCER; WOMENS HEALTH; LIFE-STYLE; COHORT AB IMPORTANCE The 2008 Physical Activity Guidelines for Americans recommended a minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5 metabolic-equivalent hours per week) of aerobic activity for substantial health benefit and suggested additional benefits by doing more than double this amount. However, the upper limit of longevity benefit or possible harm with more physical activity is unclear. OBJECTIVE To quantify the dose-response association between leisure time physical activity and mortality and define the upper limit of benefit or harm associated with increased levels of physical activity. DESIGN, SETTING, AND PARTICIPANTS We pooled data from 6 studies in the National Cancer Institute Cohort Consortium (baseline 1992-2003). Population-based prospective cohorts in the United States and Europe with self-reported physical activity were analyzed in 2014. A total of 661 137 men and women (median age, 62 years; range, 21-98 years) and 116 686 deaths were included. We used Cox proportional hazards regression with cohort stratification to generate multivariable-adjusted hazard ratios (HRs) and 95% CIs. Median follow-up time was 14.2 years. EXPOSURES Leisure time moderate- to vigorous-intensity physical activity. MAIN OUTCOMES AND MEASURES The upper limit of mortality benefit from high levels of leisure time physical activity. RESULTS Compared with individuals reporting no leisure time physical activity, we observed a 20% lower mortality risk among those performing less than the recommended minimum of 7.5metabolic-equivalent hours per week (HR, 0.80 [95% CI, 0.78-0.82]), a 31% lower risk at 1 to 2 times the recommended minimum (HR, 0.69 [95% CI, 0.67-0.70]), and a 37% lower risk at 2 to 3 times the minimum (HR, 0.63 [95% CI, 0.62-0.65]). An upper threshold for mortality benefit occurred at 3 to 5 times the physical activity recommendation (HR, 0.61 [95% CI, 0.59-0.62]); however, compared with the recommended minimum, the additional benefit was modest (31% vs 39%). There was no evidence of harm at 10 or more times the recommended minimum (HR, 0.69 [95% CI, 0.59-0.78]). A similar dose-response relationship was observed for mortality due to cardiovascular disease and to cancer. CONCLUSIONS AND RELEVANCE Meeting the 2008 Physical Activity Guidelines for Americans minimum by either moderate- or vigorous-intensity activities was associated with nearly the maximum longevity benefit. We observed a benefit threshold at approximately 3 to 5 times the recommended leisure time physical activity minimum and no excess risk at 10 or more times the minimum. In regard to mortality, health care professionals should encourage inactive adults to perform leisure time physical activity and do not need to discourage adults who already participate in high-activity levels. C1 [Arem, Hannah; Moore, Steven C.; Hartge, Patricia; de Gonzalez, Amy Berrington; Freedman, Michal; Linet, Martha S.; Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Patel, Alpa; Campbell, Peter T.] Amer Canc Soc, Atlanta, GA 30329 USA. [Visvanathan, Kala] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Weiderpass, Elisabete; Adami, Hans Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Weiderpass, Elisabete] Arctic Univ Norway, Univ Tromso, Dept Community Med, Tromso, Norway. [Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway. [Weiderpass, Elisabete] Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki, Finland. [Adami, Hans Olov] Harvard Univ, Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lee, I. -Min] Harvard Univ, Harvard Med Sch, Dept Med, Boston, MA 02115 USA. RP Arem, H (reprint author), Natl Canc Inst Shady Grove, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E314,MSC 9768, Bethesda, MD 20892 USA. EM hannah.arem@nih.gov RI Moore, Steven/D-8760-2016; Weiderpass, Elisabete/M-4029-2016 OI Moore, Steven/0000-0002-8169-1661; Weiderpass, Elisabete/0000-0003-2237-0128 FU Division of Cancer Epidemiology and Genetics, US National Institutes of Health (NIH), National Cancer Institute (NCI); Division of Cancer Control and Population Sciences, US National Institutes of Health (NIH), National Cancer Institute (NCI); Intramural Research Program of the NCI; National Institute of Aging grant [U01 AG18033]; NCI grant [CA105069]; Intramural Research Program at the American Cancer Society; Intramural Research Program, Division of Cancer Epidemiology and Genetics, NCI; NCI [CA047988]; National Heart, Lung, and Blood Institute [HL043851, HL080467, HL099355]; Swedish Research Council grant [521-2011-2955] FX This study was supported in part by the Intramural Research Program in the Division of Cancer Epidemiology and Genetics and the Division of Cancer Control and Population Sciences, both of the US National Institutes of Health (NIH), National Cancer Institute (NCI). The NIH-AARP (formerly American Association of Retired Persons) Diet and Health study was supported by the Intramural Research Program of the NCI. The Campaign against Cancer and Stroke II was supported by National Institute of Aging grant U01 AG18033 and NCI grant CA105069. The CPS II was supported by the Intramural Research Program at the American Cancer Society. The US Radiologic Technologists study was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, NCI. The Women's Health Study was supported by grant CA047988 from the NCI and grants HL043851, HL080467, and HL099355 from the National Heart, Lung, and Blood Institute. The Swedish Women's Lifestyle and Health study is supported by Swedish Research Council grant 521-2011-2955. NR 42 TC 91 Z9 91 U1 17 U2 43 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN PY 2015 VL 175 IS 6 BP 959 EP 967 DI 10.1001/jamainternmed.2015.0533 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CK4GD UT WOS:000356180400022 PM 25844730 ER PT J AU Asvold, BO Vatten, LJ Bjoro, T Bauer, DC Bremner, A Cappola, AR Ceresini, G den Elzen, WPJ Ferrucci, L Franco, OH Franklyn, JA Gussekloo, J Iervasi, G Imaizumi, M Kearney, PM Khaw, KT Maciel, RMB Newman, AB Peeters, RP Psaty, BM Razvi, S Sgarbi, JA Stott, DJ Trompet, S Vanderpump, MPJ Volzke, H Walsh, JP Westendorp, RGJ Rodondi, N AF Asvold, Bjorn O. Vatten, Lars J. Bjoro, Trine Bauer, Douglas C. Bremner, Alexandra Cappola, Anne R. Ceresini, Graziano den Elzen, Wendy P. J. Ferrucci, Luigi Franco, Oscar H. Franklyn, Jayne A. Gussekloo, Jacobijn Iervasi, Giorgio Imaizumi, Misa Kearney, Patricia M. Khaw, Kay-Tee Maciel, Rui M. B. Newman, Anne. B. Peeters, Robin P. Psaty, Bruce M. Razvi, Salman Sgarbi, Jose A. Stott, David J. Trompet, Stella Vanderpump, Mark P. J. Voelzke, Henry Walsh, John P. Westendorp, Rudi G. J. Rodondi, Nicolas CA Thyroid Studies Collaboration TI Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease An Individual Participant Data Analysis of 14 Cohorts SO JAMA INTERNAL MEDICINE LA English DT Article ID THYROTROPIN REFERENCE RANGE; KANGBUK SAMSUNG HEALTH; ALL-CAUSE MORTALITY; 11-YEAR FOLLOW-UP; SUBCLINICAL HYPOTHYROIDISM; FREE-THYROXINE; STIMULATING HORMONE; CARDIOVASCULAR RISK; SERUM TSH; OLDER MEN AB IMPORTANCE Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). OBJECTIVE To assess the association between differences in thyroid function within the reference range and CHD risk. DESIGN, SETTING, AND PARTICIPANTS Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55 412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. EXPOSURES Thyroid function as expressed by serum thyrotropin levels at baseline. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. RESULTS Among 55 412 individuals, 1813 people (3.3%) died of CHD during 643 183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48 875 individuals (9.5%) experienced a first-time CHD event during 533 408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. CONCLUSIONS AND RELEVANCE Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit. C1 [Asvold, Bjorn O.; Vatten, Lars J.] Norwegian Univ Sci & Technol, Dept Publ Hlth, N-7491 Trondheim, Norway. [Asvold, Bjorn O.] Univ Trondheim Hosp, St Olavs Hosp, Dept Endocrinol, Trondheim, Norway. [Vatten, Lars J.] Harvard Univ, Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bjoro, Trine] Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway. [Bjoro, Trine] Univ Oslo, Fac Med, Oslo, Norway. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bremner, Alexandra] Univ Western Australia, Sch Populat Hlth, Crawley, WA, Australia. [Cappola, Anne R.] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Ceresini, Graziano] Univ Hosp Parma, Dept Clin & Expt Med, Geriatr Endocrine Unit, Parma, Italy. [den Elzen, Wendy P. J.; Gussekloo, Jacobijn] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands. [Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. [Franco, Oscar H.; Peeters, Robin P.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Franklyn, Jayne A.] Univ Birmingham, Coll Med & Dent Sci, Sch Clin & Expt Med, Birmingham, W Midlands, England. [Iervasi, Giorgio] Tuscany Reg G Monasterio Fdn, Natl Council Res Inst Clin Physiol, Pisa, Italy. [Imaizumi, Misa] Radiat Effects Res Fdn, Dept Clin Studies, Nagasaki, Japan. [Kearney, Patricia M.] Natl Univ Ireland Univ Coll Cork, Dept Epidemiol & Publ Hlth, Cork, Ireland. [Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Maciel, Rui M. B.; Sgarbi, Jose A.] Univ Fed Sao Paulo, Dept Med, Div Endocrinol, Sao Paulo, SP, Brazil. [Newman, Anne. B.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Rotterdam Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Rotterdam Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Rotterdam Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Razvi, Salman] Gateshead Hlth Fdn Natl Hlth Serv Trust, Dept Endocrinol, Gateshead, England. [Sgarbi, Jose A.] Fac Med Marilia, Div Endocrinol, Marilia, Brazil. [Stott, David J.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Trompet, Stella] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Trompet, Stella; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Vanderpump, Mark P. J.] Royal Free Hosp, Dept Endocrinol, London NW3 2QG, England. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Study Hlth Pomerania Clin Epidemiol Res, Greifswald, Germany. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, German Ctr Cardiovasc Res, Greifswald, Germany. [Walsh, John P.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia. [Walsh, John P.] Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia. [Westendorp, Rudi G. J.] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Westendorp, Rudi G. J.] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark. [Rodondi, Nicolas] Univ Bern, Inselspital, Dept Gen Internal Med, CH-3010 Bern, Switzerland. RP Asvold, BO (reprint author), Norwegian Univ Sci & Technol, Dept Publ Hlth, Postboks 8905 MTFS, N-7491 Trondheim, Norway. EM bjorn.o.asvold@ntnu.no RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU Swiss National Science Foundation (SNSF) [320030-138267, 320030-150025]; Swiss Heart Foundation; Research Council of Norway; UK Department of Health; Erasmus MC; Erasmus University, Rotterdam, the Netherlands; Netherlands Organisation for Scientific Research; Netherlands Organisation for the Health Research and Development; Research Institute for Diseases in the Elderly; Ministry of Education, Culture, and Science; Ministry for Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; AXA Research Fund; Netherlands Organisation for Health Research and Development (HTA grant) [80.82500.98.10208]; Nestle Nutrition (Nestec Ltd); Metagenics Inc; AXA; Dutch Ministry of Health, Welfare, and Sports; Radiation Effects Research Foundation, Hiroshima, Japan; Radiation Effects Research Foundation, Nagasaki, Japan; Japanese Ministry of Health, Labor, and Welfare; US Department of Energy; National Academy of Sciences; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA grant [R01-AG028050]; National Institute of Nursing Research grant [R01-NR012459]; Intramural Research Program of the NH NIA; National Heart, Lung, and Blood Institute [HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute of Neurological Disorders and Stroke; NIA [AG-032317, AG-023629]; Wallac Oy (Turku, Finland); Medical Research Council UK; Cancer Research UK; Sao Paulo State Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo grant) [6/59737-9]; Federal Ministry of Education and Research; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; German Research Foundation [DFG Vo 955/12-1]; Bristol-Myers Squibb; Netherlands Heart Foundation [2001 D 032]; National Institutes of Health (NIH); NIA; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Center for Advancing Translational Sciences; NIH Roadmap for Medical Research [U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128] FX The Thyroid Studies Collaboration was supported by grants from the Swiss National Science Foundation (SNSF 320030-138267 and 320030-150025) and partially supported by a grant from the Swiss Heart Foundation (all to Dr Rodondi). Dr Asvold is supported by the Research Council of Norway. The Whickham Survey was supported by the UK Department of Health. The Rotterdam Study is funded by Erasmus MC and Erasmus University, Rotterdam, the Netherlands; the Netherlands Organisation for Scientific Research; the Netherlands Organisation for the Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture, and Science; the Ministry for Health, Welfare, and Sports; the European Commission; and the Municipality of Rotterdam. Maryam Kavousi, MD, PhD (Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands), is supported by the AXA Research Fund. Maarten J. G. Leening, MD, MSc, and Bruno H. Stricker, MMed, PhD (both with Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands), are supported by a grant from the Netherlands Organisation for Health Research and Development (HTA grant 80.82500.98.10208). Dr Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestle Nutrition (Nestec Ltd), Metagenics Inc, and AXA. The Leiden 85-Plus Study was partly funded by the Dutch Ministry of Health, Welfare, and Sports. The Nagasaki Adult Health Study was supported by the Radiation Effects Research Foundation, Hiroshima and Nagasaki, Japan, a private, nonprofit foundation funded by the Japanese Ministry of Health, Labor, and Welfare and the US Department of Energy, the latter in part through the National Academy of Sciences. The Health, Aging, and Body Composition Study was supported by National Institute on Aging (NIA) contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; NIA grant R01-AG028050; and National Institute of Nursing Research grant R01-NR012459. The research was supported in part by the Intramural Research Program of the NH NIA. Principal investigators and staff of the Health, Aging, and Body Composition Study are Anne B. Newman, MD, MPH, and Diane Ives, MPH, University of Pittsburgh; Suzanne Satterfield, MD, DrPH, and Jan Elam, BS, University of Tennessee, Memphis; Steven R. Cummings, MD, Michael C. Nevitt, PhD, and Susan M. Rubin, MPH, University of California, San Francisco; and Tamara B. Harris, MD, and Melissa E. Garcia, MPH, National Institute on Aging. The Cardiovascular Health Study (CHS) is supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 as well as grant HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-032317 and AG-023629 from the NIA (see also https://chs-nhlbi.org/). The Nord-Trondelag Health Study (HUNT Study) is a collaborative effort of HUNT Research Center, Faculty of Medicine, Norwegian University of Science and Technology; Nord-Trondelag County Council; Central Norway Health Authority; and the Norwegian Institute of Public Health. Data were provided by the HUNT Research Center, Statistics Norway, and the Department for Research and Development, Nord-Trondelag Hospital Trust. The thyroid function testing in the HUNT Study was financially supported by Wallac Oy (Turku, Finland).; The EPIC-Norfolk Study was supported by research grants from the Medical Research Council UK and Cancer Research UK. The Brazilian Thyroid Study was supported by an unrestricted grant from the Sao Paulo State Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo grant 6/59737-9 to Dr Maciel). The Study of Health in Pomerania is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research, the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Analyses were further supported by a grant of the German Research Foundation (DFG Vo 955/12-1). The Prospective Study of Pravastatin in the Elderly at Risk study was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. Dr Jukema is an established clinical investigator of the Netherlands Heart Foundation (grant 2001 D 032). The Osteoporotic Fractures in Men Study is supported by National Institutes of Health (NIH) funding. The following institutes provide support: the NIA, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. NR 66 TC 11 Z9 11 U1 1 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN PY 2015 VL 175 IS 6 BP 1037 EP 1047 DI 10.1001/jamainternmed.2015.0930 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CK4GD UT WOS:000356180400036 PM 25893284 ER PT J AU Baker, SG AF Baker, Stuart G. TI RE: Combined Associations of Genetic and Environmental Risk Factors: Implications for Prevention of Breast Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID RELATIVE UTILITY CURVES; PREDICTION C1 [Baker, Stuart G.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, 9609 Med Ctr Dr,5E638,MSC 9789, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 6 TC 0 Z9 0 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUN PY 2015 VL 107 IS 6 AR djv127 DI 10.1093/jnci/djv127 PG 2 WC Oncology SC Oncology GA CK5EG UT WOS:000356244500021 PM 25957379 ER PT J AU Beaber, EF Kim, JJ Schapira, MM Tosteson, ANA Zauber, AG Geiger, AM Kamineni, A Weaver, DL Tiro, JA AF Beaber, Elisabeth F. Kim, Jane J. Schapira, Marilyn M. Tosteson, Anna N. A. Zauber, Ann G. Geiger, Ann M. Kamineni, Aruna Weaver, Donald L. Tiro, Jasmin A. CA Population-Based Res Optimizing TI Unifying Screening Processes Within the PROSPR Consortium: A Conceptual Model for Breast, Cervical, and Colorectal Cancer Screening SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SERVICES TASK-FORCE; COMMON DATA ELEMENTS; TIMELY FOLLOW-UP; RECOMMENDATION STATEMENT; PERSONALIZED REGIMENS; RESEARCH PERSPECTIVE; SOCIETY GUIDELINES; MULTILEVEL FACTORS; CARE CONTINUUM; TISSUE-BANK AB General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites. C1 [Beaber, Elisabeth F.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Kim, Jane J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Schapira, Marilyn M.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Tosteson, Anna N. A.] Dartmouth & Norris Cotton Canc Ctr, Geisel Sch Med, Dept Med, Lebanon, NH USA. [Tosteson, Anna N. A.] Dartmouth & Norris Cotton Canc Ctr, Geisel Sch Med, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Geiger, Ann M.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Kamineni, Aruna] Grp Hlth Res Inst, Seattle, WA USA. [Weaver, Donald L.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Weaver, Donald L.] Univ Vermont, Ctr Canc, Burlington, VT USA. [Tiro, Jasmin A.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. RP Beaber, EF (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-A306,POB 19024, Seattle, WA 98109 USA. EM ebeaber@fredhutch.org OI Tiro, Jasmin/0000-0001-8300-0441 FU NCI NIH HHS [U54CA163308-04S1, 54CA163262-04S1, P30 CA008748, P30 CA023108, U01 CA163304, U01CA163304, U54 CA163261, U54 CA163262, U54 CA163303, U54 CA163307, U54 CA163308, U54 CA163313, U54 CA164336, U54CA163261, U54CA163261-04S1, U54CA163262, U54CA163303, U54CA163307, U54CA163308, U54CA163313, U54CA164336] NR 67 TC 6 Z9 6 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUN PY 2015 VL 107 IS 6 AR djv120 DI 10.1093/jnci/djv120 PG 8 WC Oncology SC Oncology GA CK5EG UT WOS:000356244500019 PM 25957378 ER PT J AU Consonni, D Pierobon, M Gail, MH Rubagotti, M Rotunno, M Goldstein, A Goldin, L Lubin, J Wacholder, S Caporaso, NE Bertazzi, PA Tucker, MA Pesatori, AC Landi, MT AF Consonni, Dario Pierobon, Mariaelena Gail, Mitchell H. Rubagotti, Maurizia Rotunno, Melissa Goldstein, Alisa Goldin, Lynn Lubin, Jay Wacholder, Sholom Caporaso, Neil E. Bertazzi, Pier Alberto Tucker, Margaret A. Pesatori, Angela C. Landi, Maria Teresa TI Lung Cancer Prognosis Before and After Recurrence in a Population-Based Setting SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FORTHCOMING 7TH EDITION; LOCAL RECURRENCE; INTERNATIONAL ASSOCIATION; TNM CLASSIFICATION; COMPLETE RESECTION; MALIGNANT-TUMORS; BRAIN METASTASES; STAGE GROUPINGS; RISK-FACTORS; SURGERY AB Background: Population-based estimates of absolute risk of lung cancer recurrence, and of mortality rates after recurrence, can inform clinical management. Methods: We evaluated prognostic factors for recurrences and survival in 2098 lung cancer case patients from the general population of Lombardy, Italy, from 2002 to 2005. We conducted survival analyses and estimated absolute risks separately for stage IA to IIIA surgically treated and stage IIIB to IV non-surgically treated patients. Results: Absolute risk of metastases exceeded that of local recurrence in every stage and cell type, highlighting the systemic threat of lung cancer. In stage I, the probability of dying within the first year after diagnosis was 2.7%, but it was 48.3% within first year after recurrence; in stage IV, the probabilities were 57.3% and 80.6%, respectively. Over half the patients died within one year of first metastasis. Although in stages IA to IB about one-third of patients had a recurrence, stage IIA patients had a recurrence risk (61.2%) similar to stage IIB (57.9%) and IIIA (62.8%) patients. Risk of brain metastases in stage IA to IIIA surgically treated non-small cell lung cancer patients increased with increasing tumor grade. Absolute risk of recurrence was virtually identical in adenocarcinoma and squamous cell carcinoma patients. Conclusions: This population-based study provides clinically useful estimates of risks of lung cancer recurrence and mortality that are applicable to the general population. These data highlight the need for more effective adjuvant treatments overall and within specific subgroups. The estimated risks of various endpoints are useful for designing clinical trials, whose power depends on absolute numbers of events. C1 [Consonni, Dario; Bertazzi, Pier Alberto; Pesatori, Angela C.] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, Milan, Italy. [Pierobon, Mariaelena] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. [Pierobon, Mariaelena; Rotunno, Melissa; Goldstein, Alisa; Goldin, Lynn; Caporaso, Neil E.; Tucker, Margaret A.; Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Gail, Mitchell H.; Lubin, Jay; Wacholder, Sholom] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Biostat Branch, Bethesda, MD 20892 USA. [Rubagotti, Maurizia; Bertazzi, Pier Alberto; Pesatori, Angela C.] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,RM 6-E446,MSC 9780, Rockville, MD 20850 USA. EM gailm@mail.nih.gov; landim@mail.nih.gov RI Consonni, Dario/K-7943-2016; bertazzi, pietro alberto/D-5039-2017; OI Consonni, Dario/0000-0002-8935-3843; bertazzi, pietro alberto/0000-0003-3475-2449; pesatori, angela/0000-0002-0261-3252 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute, Division of Cancer Epidemiology and Genetics; Lombardy Region, Italy [14013-2010]; Italian Ministry of Health and INAIL [PMS/42/06] FX This work was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics; the Lombardy Region, Italy (program 14013-2010); and the Italian Ministry of Health and INAIL (PMS/42/06). NR 32 TC 7 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUN PY 2015 VL 107 IS 6 AR djv059 DI 10.1093/jnci/djv059 PG 12 WC Oncology SC Oncology GA CK5EG UT WOS:000356244500005 PM 25802059 ER PT J AU Giuliano, AR Kreimer, AR de Sanjose, S AF Giuliano, Anna R. Kreimer, Aimee R. de Sanjose, Silvia TI The Beginning of the End: Vaccine Prevention of HPV-Driven Cancers SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID IMMUNIZATION PRACTICES ACIP; HUMAN-PAPILLOMAVIRUS; INTRAEPITHELIAL NEOPLASIA; ADVISORY-COMMITTEE; NECK-CANCER; INFECTION; HEAD; RECOMMENDATIONS; EFFICACY; TRENDS C1 [Giuliano, Anna R.] H Lee Moffitt Canc Ctr & Res Inst, Ctr Infect Res Canc, Tampa, FL 33612 USA. [Kreimer, Aimee R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [de Sanjose, Silvia] IDIBELL, Canc Epidemiol Res Programme, Catalan Inst Oncol, Barcelona, Spain. [de Sanjose, Silvia] CIBER Epidemiol & Salut Publ, Barcelona, Spain. RP Giuliano, AR (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Ctr Infect Res Canc, MRC CAN CONT, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM anna.giuliano@moffitt.org RI de Sanjose Llongueras, Silvia/H-6339-2014 NR 22 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUN PY 2015 VL 107 IS 6 AR djv128 DI 10.1093/jnci/djv128 PG 2 WC Oncology SC Oncology GA CK5EG UT WOS:000356244500022 PM 25911509 ER PT J AU Kohler, BA Sherman, RL Howlader, N Jemal, A Ryerson, AB Henry, KA Boscoe, FP Cronin, KA Lake, A Noone, AM Henley, SJ Eheman, CR Anderson, RN Penberthy, L AF Kohler, Betsy A. Sherman, Recinda L. Howlader, Nadia Jemal, Ahmedin Ryerson, A. Blythe Henry, Kevin A. Boscoe, Francis P. Cronin, Kathleen A. Lake, Andrew Noone, Anne-Michelle Henley, S. Jane Eheman, Christie R. Anderson, Robert N. Penberthy, Lynne TI Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID AFRICAN-AMERICAN WOMEN; AGE-SPECIFIC INCIDENCE; DISPARITIES GEOCODING PROJECT; BLACK-WHITE CROSSOVER; UNITED-STATES; INCIDENCE RATES; SOCIOECONOMIC-STATUS; COLORECTAL-CANCER; SURVEILLANCE DATA; PROSTATE-CANCER AB Background: The American Cancer Society (ACS), Centers for Disease Control and Prevention (CDC), National Cancer Institute (NCI), and North American Association of Central Cancer Registries (NAACCR) collaborate annually to produce updated, national cancer statistics. This Annual Report includes a focus on breast cancer incidence by subtype using new, national-level data. Methods: Population-based cancer trends and breast cancer incidence by molecular subtype were calculated. Breast cancer subtypes were classified using tumor biomarkers for hormone receptor (HR) and human growth factor-neu receptor (HER2) expression. Results: Overall cancer incidence decreased for men by 1.8% annually from 2007 to 2011. Rates for women were stable from 1998 to 2011. Within these trends there was racial/ethnic variation, and some sites have increasing rates. Among children, incidence rates continued to increase by 0.8% per year over the past decade while, like adults, mortality declined. Overall mortality has been declining for both men and women since the early 1990's and for children since the 1970's. HR+/HER2-breast cancers, the subtype with the best prognosis, were the most common for all races/ethnicities with highest rates among non-Hispanic white women, local stage cases, and low poverty areas (92.7, 63.51, and 98.69 per 100 000 non-Hispanic white women, respectively). HR+/HER2-breast cancer incidence rates were strongly, positively correlated with mammography use, particularly for non-Hispanic white women (Pearson 0.57, two-sided P <.001). Triple-negative breast cancers, the subtype with the worst prognosis, were highest among non-Hispanic black women (27.2 per 100 000 non-Hispanic black women), which is reflected in high rates in southeastern states. Conclusions: Progress continues in reducing the burden of cancer in the United States. There are unique racial/ethnic-specific incidence patterns for breast cancer subtypes; likely because of both biologic and social risk factors, including variation in mammography use. Breast cancer subtype analysis confirms the capacity of cancer registries to adjust national collection standards to produce clinically relevant data based on evolving medical knowledge. C1 [Kohler, Betsy A.; Sherman, Recinda L.; Henry, Kevin A.; Boscoe, Francis P.] North Amer Assoc Cent Canc Registries, Springfield, IL 62704 USA. [Howlader, Nadia; Cronin, Kathleen A.; Noone, Anne-Michelle; Penberthy, Lynne] NCI, Bethesda, MD 20892 USA. [Jemal, Ahmedin] Amer Canc Soc, Atlanta, GA 30329 USA. [Ryerson, A. Blythe; Henley, S. Jane; Eheman, Christie R.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Henry, Kevin A.] Temple Univ, Dept Geog, Philadelphia, PA 19122 USA. [Boscoe, Francis P.] New York State Canc Registry, New York, NY USA. [Lake, Andrew] Information Management Serv Inc, Rockville, MD USA. [Anderson, Robert N.] Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Kohler, BA (reprint author), North Amer Assoc Cent Canc Registries, 2121 West White Oaks Dr,Suite B, Springfield, IL 62704 USA. EM bkohler@naaccr.org FU American Cancer Society; Centers for Disease Control and Prevention; National Cancer Institute; North American Association of Central Cancer Registries FX This work was supported by the American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries. NR 105 TC 87 Z9 89 U1 11 U2 30 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUN PY 2015 VL 107 IS 6 AR djv048 DI 10.1093/jnci/djv048 PG 25 WC Oncology SC Oncology GA CK5EG UT WOS:000356244500002 PM 25825511 ER PT J AU Saraiya, M Unger, ER Thompson, TD Lynch, CF Hernandez, BY Lyu, CW Steinau, M Watson, M Wilkinson, EJ Hopenhayn, C Copeland, G Cozen, W Peters, ES Huang, YJ Saber, MS Altekruse, S Goodman, MT AF Saraiya, Mona Unger, Elizabeth R. Thompson, Trevor D. Lynch, Charles F. Hernandez, Brenda Y. Lyu, Christopher W. Steinau, Martin Watson, Meg Wilkinson, Edward J. Hopenhayn, Claudia Copeland, Glenn Cozen, Wendy Peters, Edward S. Huang, Youjie Saber, Maria Sibug Altekruse, Sean Goodman, Marc T. CA HPV Typing Canc Workgrp TI US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-PAPILLOMAVIRUS TYPES; INVASIVE CERVICAL-CANCER; UNITED-STATES; INTRAEPITHELIAL NEOPLASIA; VACCINATION COVERAGE; PREVALENCE; INFECTION; WORLDWIDE; IMPACT; ATTRIBUTION AB Background: This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. Methods: The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. Results: HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. Conclusions: In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine. C1 [Saraiya, Mona; Thompson, Trevor D.; Watson, Meg] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Unger, Elizabeth R.; Steinau, Martin] Ctr Dis Control & Prevent, Div High Consequence Pathogens & Pathol, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30341 USA. [Hernandez, Brenda Y.; Goodman, Marc T.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Cozen, Wendy] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Cozen, Wendy; Saber, Maria Sibug] Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. [Peters, Edward S.] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Dept Epidemiol, New Orleans, LA USA. [Wilkinson, Edward J.] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. [Copeland, Glenn] Michigan Dept Community Hlth, Lansing, MI USA. [Hopenhayn, Claudia] Univ Kentucky, Coll Publ Hlth, Dept Epidemiol, Lexington, KY USA. [Huang, Youjie] Florida Dept Hlth, Tallahassee, FL USA. [Altekruse, Sean] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Lyu, Christopher W.] Battelle Mem Inst, Durham, NC USA. [Altekruse, Sean] NCI, Bethesda, MD 20892 USA. RP Saraiya, M (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Hwy,MS F-76, Atlanta, GA 30341 USA. EM msaraiya@cdc.gov OI /0000-0003-4928-6532 FU National Program of Cancer Registries and Surveillance, Epidemiology, and End Results (SEER); Centers for Disease Control and Prevention via in-kind funds [200-2002-00573]; California Department of Health Services; National Cancer Institute, National Institutes of Health, Department of Health and Human Services [N01-PC-2010-00035, 1U58DP000807-3]; SEER Program, National Institutes of Health, Department of Health and Human Services [N01-PC-35139, N01-PC-35143, N01-PC-35137] FX The support for collection of original specimens from non-repositories (Kentucky, Florida, Michigan, Louisiana); coordination of genotyping data from registries funded, in part, by the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results (SEER); and genotyping was largely supported by the Centers for Disease Control and Prevention (CDC).; This project was largely supported by the Centers for Disease Control and Prevention via in-kind funds, intramural funds to CDC human papillomavirus (HPV) lab, and contract (# 200-2002-00573, Task Order 0018). The support for coordination of genotyping data and genotyping was largely supported by CDC intramural funds via a contract. The collection of routine cancer registry data from California was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services under Contract N01-PC-2010-00035, and cooperative agreement number 1U58DP000807-3. The support of the repositories and staff came from the SEER Program, National Institutes of Health, Department of Health and Human Services, under Contracts N01-PC-35139 (Los Angeles), N01-PC-35143 (Iowa), and N01-PC-35137 (Hawaii). NR 46 TC 29 Z9 30 U1 9 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUN PY 2015 VL 107 IS 6 AR djv086 DI 10.1093/jnci/djv086 PG 12 WC Oncology SC Oncology GA CK5EG UT WOS:000356244500013 PM 25925419 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI The Turbulent Network Dynamics of Microbial Evolution and the Statistical Tree of Life SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Review DE Microbial evolution; Phylogenetic trees; Horizontal gene transfer; Muller's ratchet; Evolvability ID HORIZONTAL GENE-TRANSFER; UNIVERSAL COMMON ANCESTOR; GENOME EVOLUTION; FREQUENCY DISTRIBUTIONS; PHYLOGENETIC FOREST; MULLERS RATCHET; PAN-GENOME; MODEL; PROKARYOTES; ARCHAEA AB The wide spread and high rate of gene exchange and loss in the prokaryotic world translate into "network genomics". The rates of gene gain and loss are comparable with the rate of point mutations but are substantially greater than the duplication rate. Thus, evolution of prokaryotes is primarily shaped by gene gain and loss. These processes are essential to prevent mutational meltdown of microbial populations by stopping Muller's ratchet and appear to trigger emergence of major novel clades by opening up new ecological niches. At least some bacteria and archaea seem to have evolved dedicated devices for gene transfer. Despite the dominance of gene gain and loss, evolution of genes is intrinsically tree-like. The significant coherence between the topologies of numerous gene trees, particularly those for (nearly) universal genes, is compatible with the concept of a statistical tree of life, which forms the framework for reconstruction of the evolutionary processes in the prokaryotic world. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU US Department of Health and Human Services FX The author's research is supported by intramural Funds of the US Department of Health and Human Services (to the National Library of Medicine). NR 56 TC 6 Z9 6 U1 8 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 EI 1432-1432 J9 J MOL EVOL JI J. Mol. Evol. PD JUN PY 2015 VL 80 IS 5-6 BP 244 EP 250 DI 10.1007/s00239-015-9679-7 PG 7 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA CK9AQ UT WOS:000356532400002 PM 25894542 ER PT J AU Lewis, MA Zhao, FM Jones, D Loprinzi, CL Brell, J Weiss, M Fisch, MJ AF Lewis, Mark A. Zhao, Fengmin Jones, Desiree Loprinzi, Charles L. Brell, Joanna Weiss, Matthias Fisch, Michael J. TI Neuropathic Symptoms and Their Risk Factors in Medical Oncology Outpatients With Colorectal vs. Breast, Lung, or Prostate Cancer: Results From a Prospective Multicenter Study SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Colorectal cancer; neuropathy; neuropathic pain; numbness/tingling; oxaliplatin ID ADJUVANT TREATMENT; COLON-CANCER; OXALIPLATIN; PAIN; NEUROTOXICITY; FLUOROURACIL; LEUCOVORIN; TRIAL AB Context. Few studies have examined the prevalence and severity of treatment-induced neuropathic symptoms in patients across different cancer types. Objectives. This study aimed to report the prevalence of numbness/tingling (N/T) and neuropathic pain in patients with colorectal cancer (CRC) vs. other cancers, describe the prevalence of moderate-to-severe N/T by specific clinical variables, and examine factors associated with the presence of these symptoms. Methods. A total of 3106 outpatients with colorectal (n = 718), breast (n = 1544), lung (n = 524), or prostate (n = 320) cancer were enrolled at any point in their treatment. Assessments were conducted at the initial visit and 28-35 days later. Patients reported pain and N/T; clinicians reported mechanism of pain and ranked the top three symptoms causing difficulties. Results. Moderate-to-severe N/T was higher in patients with CRC relative to other cancer types (25.8% vs. 17.1%, P < 0.001); 25% vs. 10.5% of clinicians rated N/T as a top three symptom for patients with CRC relative to other cancers (P < 0.001). The prevalence of neuropathic pain was comparable between patients with CRC and other cancers (P = 0.654). Patients with CRC, longer duration of cancer, prior therapy, on current therapy, older patients, and patients of black race experienced worse N/T. Conclusion. Patients with CRC experience significantly higher rates of N/T but comparable neuropathic pain, relative to patients with other cancers. Awareness of the prevalence and severity of neuropathic symptoms and their associated risk factors in this patient population is critical for both clinicians and patients. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Lewis, Mark A.; Jones, Desiree; Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA. [Zhao, Fengmin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Loprinzi, Charles L.] Mayo Clin, Breast Dept, Rochester, MN USA. [Loprinzi, Charles L.] Mayo Clin, Dept Oncol, Rochester, MN USA. [Brell, Joanna] NCI, Rockville, MD USA. [Weiss, Matthias] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. RP Jones, D (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, 1515 Holcombe Blvd,Unit 410, Houston, TX 77030 USA. EM djones1@mdanderson.org FU Public Health Service [CA37604, CA17145, CA45809]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was supported in part by Public Health Service grants CA37604, CA17145, and CA45809 as well as grants from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Drs. Fisch and Zhao had full access to the data. The authors have no disclosures. NR 24 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUN PY 2015 VL 49 IS 6 BP 1016 EP 1024 DI 10.1016/j.jpainsymman.2014.11.300 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CL0BY UT WOS:000356604700010 PM 25596011 ER PT J AU Gibbs, KD Mahon, MM Truss, M Eyring, K AF Gibbs, Kenneth D., Jr. Mahon, Margaret M. Truss, Meredith Eyring, Kira TI An Assessment of Hospital-Based Palliative Care in Maryland: Infrastructure, Barriers, and Opportunities SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; infrastructure; state-level data; barriers and supports; departments of health ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; LUNG-CANCER; INTEGRATION; INTERVENTION; BENEFITS; MEDICINE; SERVICE; COSTS; TEAM AB Context. Maryland recently passed legislation mandating that hospitals with more than 50 beds have palliative care (PC) programs. Although the state's health agency can play a key role in ensuring successful implementation of this measure, there is little actionable information from which it can guide resource allocation for enhancing PC delivery statewide. Objectives. To assess the PC infrastructure at Maryland's 46 community-based nonspecialty hospitals and to describe providers' perspectives on barriers to PC and supports that could enhance PC delivery. Methods. Data on PC programs were collected using two mechanisms. First, a survey was sent to all 46 community-based hospital chief executive officers by the Maryland Cancer Collaborative. The Maryland Health Care Commission provided supplementary survey and semistructured interview data. Results. Twenty-eight hospitals (60.9%) provided information on their PC services. Eighty-nine percent of these hospitals reported the presence of a structured PC program. The profile of services provided by PC programs was largely conserved across hospital geography and size. The most common barriers reported to PC delivery were lack of knowledge among patients and/or families and lack of physician buy-in; most hospitals reported that networks and/or conferences to promote best practice sharing in PC would be useful supports. Conclusion. Systematic collection of state-level PC infrastructure data can be used to guide state health agencies' understanding of extant resources and challenges, using those data to determine resource allocation to promote the timely receipt of PC for patients and families. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Gibbs, Kenneth D., Jr.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [Gibbs, Kenneth D., Jr.] NCI, Sci Res & Technol Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Mahon, Margaret M.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Truss, Meredith] Maryland Dept Hlth & Mental Hyg, Baltimore, MD USA. [Eyring, Kira] Amer Canc Soc, Atlanta, GA 30329 USA. RP Gibbs, KD (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM kenneth.gibbs@nih.gov OI Gibbs, Kenneth/0000-0002-3532-5396 FU Centers for Disease Control and Prevention [5U58DP003919-02]; National Cancer Institute FX This work was supported by Centers for Disease Control and Prevention Cooperative Agreement Number 5U58DP003919-02. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention. Dr. Gibbs is supported by the Cancer Prevention Fellowship from the National Cancer Institute. This work was completed while Dr. Gibbs was a Master of Public Health candidate at the Johns Hopkins Bloomberg School of Public Health. The authors declare no conflicts of interest. NR 27 TC 1 Z9 1 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUN PY 2015 VL 49 IS 6 BP 1102 EP 1108 DI 10.1016/j.jpainsymman.2014.12.004 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CL0BY UT WOS:000356604700020 PM 25640276 ER PT J AU Rosendorff, C Lackland, DT Allison, M Aronow, WS Black, HR Blumenthal, RS Cannon, CP de Lemos, JA Elliott, WJ Findeiss, L Gersh, BJ Gore, JM Levy, D Long, JB O'Connor, CM O'Gara, PT Ogedegbe, O Oparil, S White, WB AF Rosendorff, Clive Lackland, Daniel T. Allison, Matthew Aronow, Wilbert S. Black, Henry R. Blumenthal, Roger S. Cannon, Christopher P. de Lemos, James A. Elliott, William J. Findeiss, Laura Gersh, Bernard J. Gore, Joel M. Levy, Daniel Long, Janet B. O'Connor, Christopher M. O'Gara, Patrick T. Ogedegbe, Olugbenga Oparil, Suzanne White, William B. CA Amer Heart Assoc Amer Coll Cardiology Amer Soc Hypertension TI Treatment of hypertension in patients with coronary artery disease SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Article DE AHA Scientific Statements; blood pressure; coronary artery disease; epidemiology; hypertension; secondary prevention ID CHRONIC HEART-FAILURE; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; ASSOCIATION TASK-FORCE; CONVERTING-ENZYME-INHIBITORS; LEFT-VENTRICULAR HYPERTROPHY; HIGH BLOOD-PRESSURE; ISOLATED SYSTOLIC HYPERTENSION; LIPID-LOWERING TREATMENT; HIGH-RISK PATIENTS C1 [Rosendorff, Clive; Lackland, Daniel T.; Allison, Matthew; Aronow, Wilbert S.; Black, Henry R.; Blumenthal, Roger S.; Cannon, Christopher P.; de Lemos, James A.; Elliott, William J.; Findeiss, Laura; Gersh, Bernard J.; Gore, Joel M.; Levy, Daniel; Long, Janet B.; O'Connor, Christopher M.; O'Gara, Patrick T.; Ogedegbe, Olugbenga; Oparil, Suzanne; White, William B.; Amer Heart Assoc; Amer Coll Cardiology; Amer Soc Hypertension] NHLBI, NIH, Bethesda, MD 20824 USA. RP Rosendorff, C (reprint author), NHLBI, NIH, Bethesda, MD 20824 USA. FU NHLBI NIH HHS [K24 HL111315] NR 284 TC 13 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 EI 1878-7436 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD JUN PY 2015 VL 9 IS 6 BP 453 EP 498 DI 10.1016/j.jash.2015.03.002 PG 46 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CK8EA UT WOS:000356470100008 PM 25840695 ER PT J AU Zhang, Q Pan, J Lubet, RA Wang, Y You, M AF Zhang, Qi Pan, Jing Lubet, Ronald A. Wang, Yian You, Ming TI Targeting the insulin-like growth factor-1 receptor by picropodophyllin for lung cancer chemoprevention SO MOLECULAR CARCINOGENESIS LA English DT Article DE IGF-1R; picropodophyllin (PPP); benzo(a)pyrene; aerosol; mouse lung tumorigenesis; chemoprevention; apoptosis ID CYCLOLIGNAN PPP; TYROSINE KINASE; POLYPHENON-E; A/J MICE; CELL; INHIBITOR; TUMORIGENESIS; APOPTOSIS; PROLIFERATION; CHEMOTHERAPY AB Insulin-like growth factor-1 receptor (IGF-1R) is a transmembrane heterotetramer that is activated by Insulin-like growth factor 1 and is crucial for tumor transformation and survival of malignant cells. Importantly, IGF-1R overexpression has been reported in many different cancers, implicating this receptor as a potential target for anticancer therapy. Picropodophyllin (PPP) is a potent inhibitor of IGF-1R and has antitumor efficacy in several cancer types. However, the chemopreventive effect of PPP in lung tumorigenesis has not been investigated. In this study, we investigated the chemopreventive activity of PPP in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and PPP was given by nasal inhalation to female A/J mice. Lung tumorigenesis was assessed by tumor multiplicity and tumor load. PPP significantly decreased tumor multiplicity and tumor load. Tumor multiplicity and load were decreased by 52% and 78% respectively by 4mg/ml aerosolized PPP. Pharmacokinetics analysis showed good bioavailability of PPP in lung and plasma. Treatment with PPP increased staining for cleaved caspase-3 and decreased Ki-67 in lung tumors, suggesting that the lung tumor inhibitory effects of PPP were partially through inhibition of proliferation and induction of apoptosis. In human lung cancer cell lines, PPP inhibited cell proliferation, and also inhibited phosphorylation of IGF-1R downstream targets, AKT and MAPK, ultimately resulting in increased apoptosis. PPP also reduced cell invasion in lung cancer cell lines. In view of our data, PPP merits further investigation as a promising chemopreventive agent for human lung cancer. (c) 2014 Wiley Periodicals, Inc. C1 [Zhang, Qi; Pan, Jing; Wang, Yian; You, Ming] Med Coll Wisconsin, Ctr Canc, Milwaukee, WI 53226 USA. [Zhang, Qi; Pan, Jing; Wang, Yian; You, Ming] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. [Lubet, Ronald A.] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RP You, M (reprint author), Med Coll Wisconsin, Ctr Canc, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. NR 36 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUN PY 2015 VL 54 SU 1 SI SI BP E129 EP E137 DI 10.1002/mc.22206 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA CK8UG UT WOS:000356513600015 PM 25163779 ER PT J AU Spong, CY AF Spong, Catherine Y. TI Prevention of the First Cesarean Delivery SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Prevention; Cesarean; Vaginal delivery; Maternal and fetal health ID MATERNAL MORTALITY; RATES; MODE AB Education of providers and patients on the importance of vaginal delivery, for the current pregnancy as well as future pregnancies, is essential to reverse the current trend of primary cesareans. When discussing cesarean with patients, counseling should include the effect on subsequent pregnancy risks including the possibility of uterine rupture and placentation abnormalities. In addition, counseling must include the concept that normal labor takes time. Re-education on the natural process of labor, the importance of allowing the time needed, and patience with the duration of pregnancy and process of labor is essential. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Spong, CY (reprint author), NICHHD, NIH, 31 Ctr Dr,Room 2A03, Bethesda, MD 20892 USA. EM spongc@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 17 TC 1 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8545 EI 1558-0474 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD JUN PY 2015 VL 42 IS 2 BP 377 EP + DI 10.1016/j.ogc.2015.01.010 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CL0LQ UT WOS:000356634600015 PM 26002173 ER PT J AU Silveira, C Muccioli, C Nussenblatt, R Belfort, R AF Silveira, Claudio Muccioli, Cristina Nussenblatt, Robert Belfort, Rubens, Jr. TI The Effect of Long-term Intermittent Trimethoprim/Sulfamethoxazole Treatment on Recurrences of Toxoplasmic Retinochoroiditis: 10 Years of Follow-up SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Editorial Material C1 [Silveira, Claudio] Clin Silveira, Erechim, RS, Brazil. [Muccioli, Cristina; Belfort, Rubens, Jr.] Univ Fed Sao Paulo, Escola Paulista Med, Dept Ophthalmol, Sao Paulo, Brazil. [Nussenblatt, Robert] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Nussenblatt, Robert] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. RP Belfort, R (reprint author), R Botucatu 821, BR-04023062 Sao Paulo, Brazil. FU Intramural NIH HHS NR 3 TC 3 Z9 3 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0927-3948 EI 1744-5078 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD JUN PY 2015 VL 23 IS 3 BP 246 EP 247 DI 10.3109/09273948.2014.964422 PG 2 WC Ophthalmology SC Ophthalmology GA CK9BZ UT WOS:000356536700009 PM 25325434 ER PT J AU Zadeh, S Pao, M Wiener, L AF Zadeh, Sima Pao, Maryland Wiener, Lori TI Opening end-of-life discussions: How to introduce Voicing My CHOiCES (TM), an advance care planning guide for adolescents and young adults SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE End of life; Palliative care; Adolescents and young adults; Advance care planning; Communication ID DECISION-MAKING; PALLIATIVE CARE; TERMINALLY-ILL; CANCER; PREFERENCES; BARRIERS; ONCOLOGY; DIGNITY AB Objective: Each year, more than 11,000 adolescents and young adults (AYAs), aged 15-34, die from cancer and other life-threatening conditions. In order to facilitate the transition from curative to end-of-life (EoL) care, it is recommended that EoL discussions be routine, begin close to the time of diagnosis, and continue throughout the illness trajectory. However, due largely to discomfort with the topic of EoL and how to approach the conversation, healthcare providers have largely avoided these discussions. Method: We conducted a two-phase study through the National Cancer Institute with AYAs living with cancer or pediatric HIV to assess AYA interest in EoL planning and to determine in which aspects of EoL planning AYAs wanted to participate. These results provided insight regarding what EoL concepts were important to AYAs, as well as preferences in terms of content, design, format, and style. The findings from this research led to the development of an age-appropriate advance care planning guide, Voicing My CHOiCES (TM). Results: Voicing My CHOiCES (TM): An Advanced Care Planning Guide for AYA became available in November 2012. This manuscript provides guidelines on how to introduce and utilize an advance care planning guide for AYAs and discusses potential barriers. Significance of Results: Successful use of Voicing My CHOiCES (TM) will depend on the comfort and skills of the healthcare provider. The present paper is intended to introduce the guide to providers who may utilize it as a resource in their practice, including physicians, nurses, social workers, chaplains, psychiatrists, and psychologists. We suggest guidelines on how to: incorporate EoL planning into the practice setting, identify timepoints at which a patient's goals of care are discussed, and address how to empower the patient and incorporate the family in EoL planning. Recommendations for introducing Voicing My CHOiCES (TM) and on how to work through each section alongside the patient are provided. C1 [Zadeh, Sima; Wiener, Lori] NCI, NIH, Bethesda, MD 20892 USA. [Pao, Maryland] NIMH, NIH, Bethesda, MD USA. RP Zadeh, S (reprint author), NCI, NIH, 10 Ctr Dr,Bldg 10,1-H Pediat Clin,Room 1-5460, Bethesda, MD 20892 USA. EM zadehsl@mail.nih.gov FU National Institutes of Health; Pediatric Oncology Branch; National Cancer Institute; Center for Cancer Research; National Institute of Mental Health FX This research was supported (in part) by the Intramural Research Programs of the National Institutes of Health, the Pediatric Oncology Branch, the National Cancer Institute, the Center for Cancer Research, and the National Institute of Mental Health. Voicing My CHOiCES (TM) was developed by the authors within the National Institute of Cancer and the National Institute of Mental Health, with the very appreciated assistance of Kathleen Samiy, Haven Battles, Ph.D, Elizabeth Ballard, Ph.D., and Melinda Merchant, M.D. NR 29 TC 8 Z9 8 U1 4 U2 17 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD JUN PY 2015 VL 13 IS 3 BP 591 EP 599 DI 10.1017/S1478951514000054 PG 9 WC Health Policy & Services SC Health Care Sciences & Services GA CK9DD UT WOS:000356539900021 PM 24622210 ER PT J AU Young, WC Nadarajah, SR Skeath, PR Berger, AM AF Young, William C. Nadarajah, Sheeba R. Skeath, Perry R. Berger, Ann M. TI Spirituality in the context of life-threatening illness and life-transforming change SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE Spirituality; Cancer; Cardiac illness; Meaning and purpose; Qualitative research ID QUALITY-OF-LIFE; CANCER SURVIVORS; CARE; PSYCHOLOGY; ONCOLOGY; RELIGION; HOSPICE; ADULTS AB Objective: Individuals with life-threatening illness often engage in some form of spirituality to meet increased needs for meaning and purpose. This study aimed to identify the role of spirituality in persons who had reported positive, life-transforming change in relation to life-threatening cancer or cardiac events, and to connect these roles to palliative and supportive care. Method: A purposive sample of 10 cardiac survivors and 9 cancer survivors was recruited. Once the participants had given informed consent and passed screening in relation to life-transforming change and distress, they engaged in a semistructured one-hour qualitative interview on the theme of how their life-transforming change occurred in the context of their life-threatening illness. In the present article, our phenomenological analysis focuses on participants' references to purpose and meaning in their lives, with particular attention to the role and context of participants' spirituality. Results: Participants mentioned spirituality, meaning, and purpose in many contexts, including connecting with family and friends, nature, art, music, and sometimes creating a relationship with God. Participants often accessed spirituality by enhancing connections in their own lives: with a higher power, people, their work, or themselves. These enhanced connections gave participants greater meaning and purpose in their lives, and substantially helped participants to adjust to their life-threatening illnesses. Significance of results: Understanding the roles and contexts of spirituality among patients with a life-threatening illness allows us to develop better palliative and supportive care plans. Spiritually oriented supportive care may include support groups, yoga, meditation, nature, music, prayer, or referral to spiritual or religious counselors. A quantitative scale is needed to help healthcare clinicians assess the spiritual and coping needs of individuals with life-threatening illness. C1 [Young, William C.; Berger, Ann M.] NIH, Pain & Palliat Care Serv, Ctr Clin, Bethesda, MD 20892 USA. [Nadarajah, Sheeba R.] Bowie State Univ, Dept Nursing, Bowie, MD USA. [Skeath, Perry R.] Univ Arizona, Arizona Ctr Integrat Med, Tucson, AZ USA. RP Berger, AM (reprint author), NIH, Pain & Palliat Care Serv, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2-1733, Bethesda, MD 20892 USA. EM aberger@cc.nih.gov FU Intramural Research training awards FX This work was funded by Intramural Research training awards to William C. Young, Sheeba Nadarajah, and Perry R. Skeath. The authors would like to thank the staff at Sub-urban Hospital and the Smith Farm Center for Healing and the Arts for their assistance. NR 39 TC 4 Z9 4 U1 3 U2 14 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD JUN PY 2015 VL 13 IS 3 BP 653 EP 660 DI 10.1017/S1478951514000340 PG 8 WC Health Policy & Services SC Health Care Sciences & Services GA CK9DD UT WOS:000356539900028 PM 24774033 ER PT J AU Holder, GN Young, WC Nadarajah, SR Berger, AM AF Holder, Gerard N. Young, William C. Nadarajah, Sheeba R. Berger, Ann M. TI Psychosocial experiences in the context of life-threatening illness: The cardiac rehabilitation patient SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE Mortality; Life-threatening illness; Cardiac illness; Qualitative research ID CORONARY-ARTERY-DISEASE; QUALITY-OF-LIFE; SOCIAL SUPPORT; HEART-DISEASE; PSYCHOLOGICAL RECOVERY; MYOCARDIAL-INFARCTION; CANCER SURVIVORS; BREAST-CANCER; DEPRESSION; DISTRESS AB Objective: One of the most prevalent life-threatening illnesses is heart disease. The initial trauma of being diagnosed with a life-threatening illness or having a cardiac event can begin a psychosocial chain reaction that results in a transformation of the lives of these patients. The goal of our study was to investigate the lived experiences of psychosocial healing in rehabilitation of cardiac patients using a qualitative written interview. Method: A purposive sample of 14 cardiac event survivors was recruited. Participants were interviewed after informed consent and screening. We used a qualitative analysis and model-revision approach similar to the procedure outlined by Charmaz (2006). Results: Participants consistently mentioned that a heightened awareness of mortality was a motivating factor that led to participants focusing more on their family and relationships, having an enhanced outlook on life, and making healthy lifestyle changes. Significance of results: If clinicians are able to employ a measure to better understand the nature of a patient's progression from cardiac event to successful recovery, interventions such as cardiac rehabilitation can be implemented earlier and more effectively during the course of the illness and recovery phases of treatment. Theoretically, this early detection of a patient's progression could reduce the time spent recovering from a cardiac event, and it would allow treatments for these conditions to better alleviate the psychosocial concerns faced by patients. C1 [Holder, Gerard N.; Young, William C.; Berger, Ann M.] NIH, Pain & Palliat Care Serv, Ctr Clin, Bethesda, MD 20892 USA. [Nadarajah, Sheeba R.] Bowie State Univ, Dept Nursing, Bowie, MD USA. RP Berger, AM (reprint author), NIH, Pain & Palliat Care Serv, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2-1733, Bethesda, MD 20892 USA. EM aberger@cc.nih.gov NR 51 TC 1 Z9 1 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD JUN PY 2015 VL 13 IS 3 BP 749 EP 756 DI 10.1017/S1478951514000583 PG 8 WC Health Policy & Services SC Health Care Sciences & Services GA CK9DD UT WOS:000356539900038 PM 24892820 ER PT J AU Goldstein, DS Sullivan, P Holmes, C Kopin, IJ Sharabi, Y Mash, DC AF Goldstein, David S. Sullivan, Patricia Holmes, Courtney Kopin, Irwin J. Sharabi, Yehonatan Mash, Deborah C. TI Decreased vesicular storage and aldehyde dehydrogenase activity in multiple system atrophy SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Multiple system atrophy; Parkinson disease; Putamen; Dopamine; Norepinephrine; DOPAL ID GLIAL CYTOPLASMIC INCLUSIONS; TOXIC DOPAMINE METABOLITE; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; CLINICAL-DIAGNOSIS; ACCURACY; DOPAL; 3,4-DIHYDROXYPHENYLACETALDEHYDE; DEFICIENCY; BIOMARKERS AB Background: Parkinson disease (PD) and multiple system atrophy (MSA) share some neuropathologic features (nigrostriatal dopaminergic lesion, alpha-synuclein deposition) but not others (Lewy bodies in PD, glial cytoplasmic inclusions in MSA). In PD evidence has accrued for a vesicular storage defect and decreased aldehyde dehydrogenase (ALDH) activity in residual dopaminergic terminals, resulting in accumulation of the toxic dopamine (DA) metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). In this study we asked whether MSA entails a similar abnormal neurochemical pattern. Methods: DA and its main neuronal metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and its main neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG), the catecholamine precursor DOPA, and DOPAL were measured in striatal and frontal cortical tissue from patients with pathologically proven end-stage MSA (N = 15), sporadic PD (N = 17), and control subjects (N = 18). Results: Compared to the control group, the MSA and PD groups had similarly decreased putamen DA (by 96% and 93%, p < 0.0001), DOPAC (97% and 95%, p < 0.0001), NE (91% and 74%, p < 0.0001), and DHPG (81% and 74%, p < 0.0001). In the MSA and PD groups, ratios of DOPAL:DA were 2.3 and 3.5 times control and DHPG:NE 3.1 and 2.6 times control, while DOPAC:DOPAL ratios were decreased by 61% and 74%. In both diseases cortical NE and DHPG were decreased, while DA and DOPAC were not. Conclusions: MSA and PD entail a catecholamine metabolic profile indicating impaired vesicular storage, decreased ALDH activity, and DOPAL buildup, which might be part of a common pathway in catecholamine neuronal death. Targeting this pathway by interfering with catecholaldehyde production or effects constitutes a novel treatment approach. Published by Elsevier Ltd. C1 [Goldstein, David S.; Sullivan, Patricia; Holmes, Courtney; Kopin, Irwin J.] NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res, Bethesda, MD 20892 USA. [Sharabi, Yehonatan] Chaim Sheba Med Ctr, Dept Internal Med, IL-52621 Tel Hashomer, Israel. [Sharabi, Yehonatan] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Mash, Deborah C.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 9000 Rockville Pike MSC-1620,Bldg 10 Room 5N220, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke (NINDS); National Institute of Mental Health (NIMH); NINDS; National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Department of Health and Human Services [HHSN271201300028C] FX The research reported here was supported by the intramural research program of the National Institute of Neurological Disorders and Stroke (NINDS).; The University of Miami Brain Endowment BankTM is funded by National Institute of Mental Health (NIMH), NINDS and National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN271201300028C. NR 28 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JUN PY 2015 VL 21 IS 6 BP 567 EP 572 DI 10.1016/j.parkreldis.2015.03.006 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CK3GX UT WOS:000356105700003 PM 25829070 ER PT J AU Jang, MK Anderson, DE van Doorslaer, K McBride, AA AF Jang, Moon Kyoo Anderson, D. Eric van Doorslaer, Koenraad McBride, Alison A. TI A proteomic approach to discover and compare interacting partners of papillomavirus E2 proteins from diverse phylogenetic groups SO PROTEOMICS LA English DT Article DE BRD4; E2; HPV; Microbiology; Papillomavirus; Virus ID RNA-BINDING; TRANSCRIPTIONAL ACTIVATION; MITOTIC CHROMOSOMES; CRYSTAL-STRUCTURE; SPLICING FACTORS; CHROMATIN; BRD4; PHOSPHORYLATION; REPLICATION; COMPLEX AB Papillomaviruses are a very successful group of viruses that replicate persistently in localized regions of the stratified epithelium of their specific host. Infection results in pathologies ranging from asymptomatic infection, benign warts, to malignant carcinomas. Despite this diversity, papillomavirus genomes are small (7-8 kbp) and contain at most eight genes. To sustain the complex papillomaviral life cycle, each viral protein has multiple functions and interacts with and manipulates a plethora of cellular proteins. In this study, we use tandem affinity purification and MS to identify host factors that interact with 11 different papillomavirus E2 proteins from diverse phylogenetic groups. The E2 proteins function in viral transcription and replication and correspondingly interact with host proteins involved in transcription, chromatin remodeling and modification, replication, and RNA processing. C1 [Jang, Moon Kyoo; van Doorslaer, Koenraad; McBride, Alison A.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. [Anderson, D. Eric] NIAID, NIH, Adv Mass Spectrometry Core, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, NIH, Room 3W20B-4,33 North Dr,MSC3209, Bethesda, MD 20892 USA. EM amcbride@nih.gov OI Van Doorslaer, Koenraad/0000-0002-2985-0733; McBride, Alison/0000-0001-5607-5157 FU Intramural Research Program of the NIAID, NIH [ZIAAI000713] FX We are grateful to Caleb McKinney and Katherine Hussmann for comments on the manuscript. This research was supported by the Intramural Research Program of the NIAID, NIH (grant number ZIAAI000713). NR 63 TC 7 Z9 7 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1615-9853 EI 1615-9861 J9 PROTEOMICS JI Proteomics PD JUN PY 2015 VL 15 IS 12 SI SI BP 2038 EP 2050 DI 10.1002/pmic.201400613 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CK6NN UT WOS:000356344900009 PM 25758368 ER PT J AU Miao, ZC Adamiak, RW Blanchet, MF Boniecki, M Bujnicki, JM Chen, SJ Cheng, C Chojnowski, G Chou, FC Cordero, P Cruz, JA Ferre-D'amare, AR Das, R Ding, F Dokholyan, NV Dunin-Horkawicz, S Kladwang, W Krokhotin, A Lach, G Magnus, M Major, F Mann, TH Masquida, B Matelska, D Meyer, M Peselis, A Popenda, M Purzycka, KJ Serganov, A Stasiewicz, J Szachniuk, M Tandon, A Tian, S Wang, J Xia, Y Xu, XJ Zhang, JW Zha, PN Zok, T Westhof, E AF Miao, Zhichao Adamiak, Ryszard W. Blanchet, Marc-Frederick Boniecki, Michal Bujnicki, Janusz M. Chen, Shi-Jie Cheng, Clarence Chojnowski, Grzegorz Chou, Fang-Chieh Cordero, Pablo Cruz, Jose Almeida Ferre-D'amare, Adrian R. Das, Rhiju Ding, Feng Dokholyan, Nikolay V. Dunin-Horkawicz, Stanislaw Kladwang, Wipapat Krokhotin, Andrey Lach, Grzegorz Magnus, Marcin Major, Francois Mann, Thomas H. Masquida, Benoit Matelska, Dorota Meyer, Melanie Peselis, Alla Popenda, Mariusz Purzycka, Katarzyna J. Serganov, Alexander Stasiewicz, Juliusz Szachniuk, Marta Tandon, Arpit Tian, Siqi Wang, Jian Xia, Yi Xu, Xiaojun Zhang, Jinwei Zha, Peinan Zok, Tomasz Westhof, Eric TI RNA-Puzzles Round II: assessment of RNA structure prediction programs applied to three large RNA structures SO RNA LA English DT Article DE 3D prediction; bioinformatics; force fields; X-ray structures; models; structure quality ID DISCRETE MOLECULAR-DYNAMICS; SECONDARY STRUCTURE PREDICTION; CRYSTAL-STRUCTURE; FOLDING THERMODYNAMICS; STRUCTURE VALIDATION; MAPPING EXPERIMENTS; GENE-EXPRESSION; ATOMIC-ACCURACY; MESSENGER-RNA; SHAPE AB This paper is a report of a second round of RNA-Puzzles, a collective and blind experiment in three-dimensional (3D) RNA structure prediction. Three puzzles, Puzzles 5, 6, and 10, represented sequences of three large RNA structures with limited or no homology with previously solved RNA molecules. A lariat-capping ribozyme, as well as riboswitches complexed to adenosylcobalamin and tRNA, were predicted by seven groups using RNAComposer, ModeRNA/SimRNA, Vfold, Rosetta, DMD, MC-Fold, 3dRNA, and AMBER refinement. Some groups derived models using data from state-of-the-art chemical-mapping methods (SHAPE, DMS, CMCT, and mutate-and-map). The comparisons between the predictions and the three subsequently released crystallographic structures, solved at diffraction resolutions of 2.5-3.2 A, were carried out automatically using various sets of quality indicators. The comparisons clearly demonstrate the state of present-day de novo prediction abilities as well as the limitations of these state-of-the-art methods. All of the best prediction models have similar topologies to the native structures, which suggests that computational methods for RNA structure prediction can already provide useful structural information for biological problems: However, the prediction accuracy for non-Watson-Crick interactions, key to proper folding of RNAs, is low and some predicted models had high Clash Scores. These two difficulties point to some of the continuing bottlenecks in RNA structure prediction. All submitted models are available for download at http://ahsoka.u-strasbg.fr/rnapuzzles/. C1 [Miao, Zhichao; Cruz, Jose Almeida; Westhof, Eric] Univ Strasbourg, Architecture & Reactiv ARN, Inst Biol Mol & Cellulaire, CNRS, F-67000 Strasbourg, France. [Adamiak, Ryszard W.; Popenda, Mariusz; Purzycka, Katarzyna J.] Polish Acad Sci, Inst Bioorgan Chem, Struct Chem Nucle Acids Lab, Dept Struct Chem & Biol Nucle Acids, PL-61704 Poznan, Poland. [Blanchet, Marc-Frederick; Major, Francois] Univ Montreal, Dept Comp Sci & Operat Res, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada. [Boniecki, Michal; Bujnicki, Janusz M.; Chojnowski, Grzegorz; Dunin-Horkawicz, Stanislaw; Lach, Grzegorz; Magnus, Marcin; Matelska, Dorota; Stasiewicz, Juliusz] Int Inst Mol & Cell Biol Warsaw, Lab Bioinformat & Prot Engn, PL-02109 Warsaw, Poland. [Bujnicki, Janusz M.] Adam Mickiewicz Univ, Fac Biol, Inst Mol Biol & Biotechnol, Lab Bioinformat, PL-61614 Poznan, Poland. [Chen, Shi-Jie; Xu, Xiaojun; Zha, Peinan] Univ Missouri, Dept Biochem, Dept Phys & Astron, Columbia, MO 65211 USA. [Chen, Shi-Jie; Xu, Xiaojun; Zha, Peinan] Univ Missouri, Inst Informat, Columbia, MO 65211 USA. [Cheng, Clarence; Chou, Fang-Chieh; Cordero, Pablo; Kladwang, Wipapat; Mann, Thomas H.; Tian, Siqi] Stanford Univ, Dept Phys, Stanford, CA 94305 USA. [Ferre-D'amare, Adrian R.; Zhang, Jinwei] NHLBI, Bethesda, MD 20892 USA. [Ding, Feng] Clemson Univ, Dept Phys & Astron, Coll Engn & Sci, Clemson, SC 29634 USA. [Dokholyan, Nikolay V.; Krokhotin, Andrey; Tandon, Arpit] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. [Masquida, Benoit] Inst Physiol & Chim Biol, Genet Mol Genom Microbiol, F-67084 Strasbourg, France. [Meyer, Melanie] Inst Genet & Biol Mol & Cellulaire, F-67400 Strasbourg, France. [Peselis, Alla; Serganov, Alexander] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA. [Szachniuk, Marta; Zok, Tomasz] Poznan Univ Tech, Inst Comp Sci, PL-60965 Poznan, Poland. [Wang, Jian] Huazhong Univ Sci & Technol, Dept Phys, Wuhan 430074, Peoples R China. RP Westhof, E (reprint author), Univ Strasbourg, Architecture & Reactiv ARN, Inst Biol Mol & Cellulaire, CNRS, F-67000 Strasbourg, France. EM e.westhof@ibmc-cnrs.unistra.fr RI Ding, Feng/G-6029-2011; Zok, Tomasz/M-1714-2014; Szachniuk, Marta/N-1991-2014; OI Ding, Feng/0000-0003-1850-6336; Zok, Tomasz/0000-0003-4103-9238; Szachniuk, Marta/0000-0002-8724-7908; Mann, Thomas/0000-0002-3821-1466; Miao, Zhichao/0000-0002-5777-9815 FU French Government [ANR-10-BINF-02-02]; French National Research Agency; National Institutes of Health (NIH) [2R01GM064803-09, 5 T32 GM007276, R01 GM102519, T32 GM088118, R21MH103655]; Burroughs-Wellcome Foundation (CAST); Bio-X fellowship; HHMI international fellowship; Stanford Graduate Fellowship; Conacyt fellowship; European Research Council [RNA+P=123D]; Foundation for Polish Science [TEAM/2009-4/2]; European Commission (EU structural funds) [POIG.02.03.00-00-003/09]; Polish National Science Centre [2012/06/A/ST6/00384, 2012/04/A/NZ2/00455]; Polish Ministry of Science and Higher Education [0492/IP1/2013/72]; NYU Whitehead fellowship; Intramural Program of the National Heart, Lung and Blood Institute-NIH FX This work (Z.M. and E.W.) is supported by the French Government grant ANR-10-BINF-02-02 BACNET. This work (E.W.) has been published under the framework of the LABEX: ANR-10-LABX-0036_NETRNA and benefits from a funding managed by the French National Research Agency as part of the Investments for the future program. N.V.D. acknowledges support of the National Institutes of Health (NIH) grant 2R01GM064803-09 (PI: K.M. Weeks). The 3D structure modeling was supported by the NIH (5 T32 GM007276 to C.C.; R01 GM102519 to R.D.), the Burroughs-Wellcome Foundation (CAST to R.D.), Bio-X and HHMI international fellowships (F.C.C.), a Stanford Graduate Fellowship (S.T.), a Conacyt fellowship (P.C.), European Research Council (grant RNA+P=123D to J.M.B.), Foundation for Polish Science (grant TEAM/2009-4/2 to J.M.B.), European Commission (EU structural funds, POIG.02.03.00-00-003/09 to J.M.B.), by the Polish National Science Centre (2012/06/A/ST6/00384 to R.W.A. and 2012/04/A/NZ2/00455 to J.M.B.) and Polish Ministry of Science and Higher Education (0492/IP1/2013/72 to K.J.P.). A.P. was supported by the NIH grant T32 GM088118. A.S. was supported by NYU Whitehead fellowship and the NIH grant R21MH103655. A.R.F. and J.Z. were supported by the Intramural Program of the National Heart, Lung and Blood Institute-NIH. NR 74 TC 36 Z9 36 U1 7 U2 31 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 EI 1469-9001 J9 RNA JI RNA PD JUN PY 2015 VL 21 IS 6 BP 1066 EP 1084 DI 10.1261/rna.049502.114 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CK6CN UT WOS:000356316200002 PM 25883046 ER PT J AU Roberts, CC Roberts, WC AF Roberts, Carey Camille Roberts, William Clifford TI Large Patent Ductus Arteriosus in a 44-Year-Old Woman Leading to Calcium Deposition in the Left Atrium and Mitral and Aortic Valves SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE Adult; calcinosis/pathology; cardiomegaly/etiology/radiography; ductus arteriosus, patent/surgery; heart atria/pathology; heart diseases/physiopathology AB This report describes unusual autopsy findings in a 44-year-old woman who had a large, calcified patent ductus arteriosus that produced substantial left-to-right shunting. The patient died in 1962, 7 days after patch closure of the aortic orifice of the ductus. Numerous calcific deposits were present in the mural left atrial endocardium, the mitral valve leaflets and annulus, and the aortic valve cusps. The cause of the left-sided calcific deposits was perhaps related to the patient's several-decades-old giant aortopulmonary shunt, causing a major increase in the volume of blood passing through the left-sided cardiac chambers in comparison with the volume in the right side. To our knowledge, such findings in a patient with patent ductus arteriosus have not been reported previously. C1 [Roberts, Carey Camille] Georgetown Univ, Sch Med, Washington, DC 20057 USA. [Roberts, Carey Camille; Roberts, William Clifford] Baylor Heart & Vasc Inst, Dallas, TX 75246 USA. [Roberts, Carey Camille] Baylor Univ, Med Ctr, Dept Internal Med, Div Cardiol, Dallas, TX 75246 USA. [Roberts, Carey Camille] Baylor Univ, Med Ctr, Dept Pathol, Dallas, TX 75246 USA. [Roberts, Carey Camille] NHLBI, Pathol Branch, Bethesda, MD 20205 USA. RP Roberts, WC (reprint author), Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, 3500 Gaston Ave, Dallas, TX 75246 USA. EM wc.roberts@baylorhealth.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 EI 1526-6702 J9 TEX HEART I J JI Tex. Heart Inst. J. PD JUN PY 2015 VL 42 IS 3 BP 262 EP 264 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CK4VZ UT WOS:000356222700018 PM 26175644 ER PT J AU Purvey, S Lu, K Mukkamalla, SK Anandi, P Dumitriu, B Kranick, S Hammoud, DA O'Connell, E Oh, AL Barrett, J Mahanty, S Battiwalla, M AF Purvey, S. Lu, K. Mukkamalla, S. K. Anandi, P. Dumitriu, B. Kranick, S. Hammoud, D. A. O'Connell, E. Oh, A. L. Barrett, J. Mahanty, S. Battiwalla, M. TI Conservative management of neurocysticercosis in a patient with hematopoietic stem cell transplantation: a case report and review SO TRANSPLANT INFECTIOUS DISEASE LA English DT Review DE allogeneic hematopoietic stem cell transplantation; neurocysticercosis; parasite; tapeworm; anthelmintics; Taenia solium ID LINKED IMMUNOELECTROTRANSFER BLOT; CEREBRAL CYSTICERCUS GRANULOMA; DOUBLE-BLIND TRIAL; TAENIA-SOLIUM; ALBENDAZOLE THERAPY; EXTRAPARENCHYMAL NEUROCYSTICERCOSIS; ANTIPARASITIC TREATMENT; SEIZURE RECURRENCE; EPILEPSY; CHILDREN AB Neurocysticercosis, an infection of the central nervous system with the larval stage of the cestode Taenia solium, is common in developing countries but its occurrence and management in allogeneic hematopoietic stem cell transplantation (HSCT) has not been reported previously, to our knowledge. We report the case of an immigrant female patient who underwent a matched-related allogeneic HSCT for acute lymphoblastic leukemia and was incidentally found to have a solitary viable neurocysticercosis lesion. However, despite severe immunosuppression, the size of the cyst did not increase. More importantly, restoration of the immune system did not induce significant inflammation or seizures. Subsequent follow-up demonstrated complete resolution of the neurocysticercosis lesion. Thus, in the setting of HSCT, an asymptomatic patient with a single neurocysticercosis lesion was successfully managed without the use of anthelmintics, steroids, or anti-epileptics. C1 [Purvey, S.; Lu, K.; Mukkamalla, S. K.; Anandi, P.; Dumitriu, B.; Barrett, J.; Battiwalla, M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Kranick, S.] NINDS, NIH, Bethesda, MD 20892 USA. [Hammoud, D. A.] NIH, Ctr Infect Dis Imaging CIDI Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [O'Connell, E.; Mahanty, S.] NIAID, NIH, Bethesda, MD 20892 USA. [Oh, A. L.] Univ Illinois, Chicago, IL USA. RP Battiwalla, M (reprint author), NHLBI, Hematol Branch, 10 Ctr Dr,Room 5-3581, Bethesda, MD 20892 USA. EM battiwam@mail.nih.gov FU NIH (National Heart, Lung, Blood Institute, National Institutes of Health); NIH (National Institute of Neurological Disorders and Stroke, Clinical Center); NIH (National Institute of Allergy and Infectious Diseases) FX This research was supported by the Intramural Research Program of the NIH (National Heart, Lung, Blood Institute, National Institutes of Health; National Institute of Neurological Disorders and Stroke, Clinical Center; National Institute of Allergy and Infectious Diseases). NR 52 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-2273 EI 1399-3062 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD JUN PY 2015 VL 17 IS 3 BP 456 EP 462 DI 10.1111/tid.12392 PG 7 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA CK2YW UT WOS:000356082600019 PM 25850995 ER PT J AU Perez, VL Caspi, RR AF Perez, Victor L. Caspi, Rachel R. TI Immune mechanisms in inflammatory and degenerative eye disease SO TRENDS IN IMMUNOLOGY LA English DT Review DE AMD; uveitis; degeneration; inflammation; parainflammation ID DELTA T-CELLS; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; OXIDATIVE DAMAGE; FAS LIGAND; AUTOIMMUNE UVEORETINITIS; TRANSGENIC MICE; ANIMAL-MODEL; MURINE MODEL; PRIVILEGE AB It has recently been recognized that pathology of age-associated degenerative eye diseases such as adult macular degeneration (AMD), glaucoma and diabetic retinopathy, have strong immunological underpinnings. Attempts have been made to extrapolate to age-related degenerative disease insights from inflammatory processes associated with non-infectious uveitis, but these have not yet been sufficiently informative. Here we review recent findings on the immune processes underlying uveitis and those that have been shown to contribute to AMD, discussing in this context parallels and differences between overt inflammation and para-inflammation in the eye. We propose that mechanisms associated with ocular immune privilege, in combination with paucity of age-related antigen(s) within the target tissue, dampen what could otherwise be overt inflammation and result in the para-inflammation that characterizes age-associated neurodegenerative disease. C1 [Perez, Victor L.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Perez, VL (reprint author), Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. EM vperez4@med.miami.edu; caspir@nei.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 FU Intramural NIH HHS [ZIA EY000184-27] NR 93 TC 18 Z9 18 U1 3 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 EI 1471-4981 J9 TRENDS IMMUNOL JI Trends Immunol. PD JUN PY 2015 VL 36 IS 6 BP 354 EP 363 DI 10.1016/j.it.2015.04.003 PG 10 WC Immunology SC Immunology GA CL0MK UT WOS:000356636600005 PM 25981967 ER PT J AU Lopata, A Jambrina, PG Sharma, PK Brooks, BR Toth, J Vertessy, BG Rosta, E AF Lopata, Anna Jambrina, Pablo G. Sharma, Pankaz K. Brooks, Bernard R. Toth, Judit Vertessy, Beata G. Rosta, Edina TI Mutations Decouple Proton Transfer from Phosphate Cleavage in the dUTPase Catalytic Reaction SO ACS CATALYSIS LA English DT Article DE QM/MM (quantum mechanics/molecular mechanics); dUTPase; continuous symmetry measure; one-metal ion catalytic mechanism; ab initio; DFT (density functional theory); coupled proton transfer ID BIFUNCTIONAL DCTP DEAMINASE; DEPENDENT PROTEIN-KINASE; INFECTIOUS-ANEMIA VIRUS; ESTER HYDROLYSIS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; LEISHMANIA-MAJOR; ACTIVE-SITE; TRIPHOSPHATE NUCLEOTIDOHYDROLASE; METHANOCALDOCOCCUS-JANNASCHII AB Most enzymes present a catalytic mechanism where one or more proton transfer events occur coupled tightly together with the enzymatic chemical reaction. We show here that inactivating mutations decouple this proton transfer step from the phosphate cleavage reaction in dUTPase. Homotrimeric dUTPase enzymes catalyze the hydrolysis of dUTP to dUMP and pyrophosphate, using largely similar structural and functional groups as most AAA+ enzymes. dUTPases typically use a single Mg2+ ion as a cofactor in the active site that is formed by direct protein protein contacts including all three protomers. Here we focus on the C-terminal arm structural motif, which has sequence and functional similarities to P-loop motifs and is required for catalysis. In this work, we have studied the functional roles of the C-terminal arm in ligand binding and catalysis by using QM/MM (quantum mechanics/molecular mechanics) calculations in conjunction with site-directed mutagenesis experiments. We also present a new method to assess the metal ion coordination symmetry during the catalytic reaction. Using this new implementation, we identified that the coordination symmetry follows a consistent pattern in the three systems studied, reaching the most symmetrical state near the transition states. We found that the phosphate cleavage proceeds with a concerted bimolecular (A(N)D(N)) mechanism with a loose dissociative transition state and that it is coupled with a proton transfer step involving a unanimously conserved Asp residue. We show that the main mechanistic effect of the lack of the C-terminal ann is to decouple the phosphate cleavage from the subsequent proton transfer step, resulting in a high-barrier altered reaction pathway. C1 [Lopata, Anna; Toth, Judit; Vertessy, Beata G.] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, H-1113 Budapest, Hungary. [Jambrina, Pablo G.; Rosta, Edina] Kings Coll London, Dept Chem, London SE1 1DB, England. [Sharma, Pankaz K.] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Seoul 120750, South Korea. [Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Rockville, MD 20892 USA. [Vertessy, Beata G.] Budapest Univ Technol & Econ, Dept Appl Biotechnol & Food Sci, H-1111 Budapest, Hungary. RP Toth, J (reprint author), Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, H-1113 Budapest, Hungary. EM tothj@enzim.hu; Vertessy.Beata@ttk.mta.hu; Edina.Rosta@kcl.ac.uk RI Jambrina, Pablo/G-8177-2015; Vertessy, Beata/H-6202-2012 OI Jambrina, Pablo/0000-0001-8846-3998; FU Intramural Research Program of the National Institutes of Health; Hungarian Scientific Research Fund [OTKA NK 84008, K109486]; Baross program of the New Hungary Development Plan [3DSTRUCT, OMFB-00266/2010 REG-KM-09-1-2009-0050]; Hungarian Academy of Sciences [TTK IF-28/2012]; European Commission FP7 Biostruct-X project [283570]; Budapest University of Technology and Economics; Korean Federation of Science and Technology Societies (KOFST) under the Brain Pool program FX This work was supported by the Intramural Research Program of the National Institutes of Health, the Hungarian Scientific Research Fund (OTKA NK 84008, K109486), the Baross program of the New Hungary Development Plan (3DSTRUCT, OMFB-00266/2010 REG-KM-09-1-2009-0050), the Hungarian Academy of Sciences (TTK IF-28/2012), and the European Commission FP7 Biostruct-X project (contract no. 283570). This work used the computational resources of the NIH biowulf duster, and the CCPBioSim via the ARCHER U.K. National Supercomputing Service. A.L. was awarded the student travel grant of the Budapest University of Technology and Economics. P.K.S. thanks Prof. Sun Choi at Ewha Womans University for laboratory facilities and the Korean Federation of Science and Technology Societies (KOFST) for a research fellowship under the Brain Pool program. NR 98 TC 6 Z9 6 U1 3 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2155-5435 J9 ACS CATAL JI ACS Catal. PD JUN PY 2015 VL 5 IS 6 BP 3225 EP 3237 DI 10.1021/cs502087f PG 13 WC Chemistry, Physical SC Chemistry GA CK1JT UT WOS:000355964300009 ER PT J AU Ma, DY Francischetti, IMB Ribeiro, JMC Andersen, JF AF Ma, Dongying Francischetti, Ivo M. B. Ribeiro, Jose M. C. Andersen, John F. TI The structure of hookworm platelet inhibitor (HPI), a CAP superfamily member from Ancylostoma caninum SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS LA English DT Article DE antigen V; hemostasis; parasitism ID NECATOR-AMERICANUS; IN-VITRO; PROTEIN; AGGREGATION; PARASITE; ANTIGEN; ALPHA(IIB)BETA(3); ANGIOGENESIS; DISINTEGRINS; REFINEMENT AB Secreted protein components of hookworm species include a number of representatives of the cysteine-rich/antigen 5/pathogenesis-related 1 (CAP) protein family known as Ancylostoma-secreted proteins (ASPs). Some of these have been considered as candidate antigens for the development of vaccines against hookworms. The functions of most CAP superfamily members are poorly understood, but one form, the hookworm platelet inhibitor (HPI), has been isolated as a putative antagonist of the platelet integrins alpha(IIb)beta(3) and alpha(2)beta(1). Here, the crystal structure of HPI is described and its structural features are examined in relation to its possible function. The HPI structure is similar to those of other ASPs and shows incomplete conservation of the sequence motifs CAP1 and CAP2 that are considered to be diagnostic of CAP superfamily members. The asymmetric unit of the HPI crystal contains a dimer with an extensive interaction interface, but chromatographic measurements indicate that it is primarily monomeric in solution. In the dimeric structure, the putative active-site cleft areas from both monomers are united into a single negatively charged depression. A potential Lys-Gly-Asp disintegrin-like motif was identified in the sequence of HPI, but is not positioned at the apex of a tight turn, making it unlikely that it interacts with the integrin. Recombinant HPI produced in Escherichia coli was found not to inhibit the adhesion of human platelets to collagen or fibrinogen, despite having a native structure as shown by X-ray diffraction. This result corroborates previous analyses of recombinant HPI and suggests that it might require post-translational modification or have a different biological function. C1 [Ma, Dongying; Francischetti, Ivo M. B.; Ribeiro, Jose M. C.; Andersen, John F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Andersen, JF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM john.andersen@nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; NIAID, National Institutes of Health FX The authors thank D. Garboczi and A. Gittis for discussions and Van Pham for technical assistance. We also thank the staff of the Southeast Regional Collaborative Access Team, Advanced Photon Source, Argonne National Laboratory for assistance with X-ray data collection. Use of the Advanced Photon Source beamlines was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under contract No. W-31-109-Eng-38. This work was supported by the intramural research program of the NIAID, National Institutes of Health. NR 32 TC 3 Z9 3 U1 0 U2 7 PU INT UNION CRYSTALLOGRAPHY PI CHESTER PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND SN 2053-230X J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Commun. PD JUN PY 2015 VL 71 BP 643 EP 649 DI 10.1107/S2053230X1500271X PN 6 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA CK1SD UT WOS:000355986700002 PM 26057788 ER PT J AU Lountos, GT Austin, BP Tropea, JE Waugh, DS AF Lountos, George T. Austin, Brian P. Tropea, Joseph E. Waugh, David S. TI Structure of human dual-specificity phosphatase 7, a potential cancer drug target SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS LA English DT Article DE dual-specificity phosphatase; DUSP; DUSP7; MAP kinase phosphatase; PTP ID PROTEIN-TYROSINE-PHOSPHATASE; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; ACUTE-LEUKEMIA; PYST2; ACTIVATION; INHIBITORS; MODEL; VHR; MAP AB Human dual-specificity phosphatase 7 (DUSP7/Pyst2) is a 320-residue protein that belongs to the mitogen-activated protein kinase phosphatase (MKP) subfamily of dual-specificity phosphatases. Although its precise biological function is still not fully understood, previous reports have demonstrated that DUSP7 is overexpressed in myeloid leukemia and other malignancies. Therefore, there is interest in developing DUSP7 inhibitors as potential therapeutic agents, especially for cancer. Here, the purification, crystallization and structure determination of the catalytic domain of DUSP7 (Ser141-Ser289/C232S) at 1.67 angstrom resolution are reported. The structure described here provides a starting point for structure-assisted inhibitor-design efforts and adds to the growing knowledge base of three-dimensional structures of the dual-specificity phosphatase family. C1 [Lountos, George T.] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Lountos, George T.; Austin, Brian P.; Tropea, Joseph E.; Waugh, David S.] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD 21702 USA. EM waughd@mail.nih.gov FU Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health under contract HHSN261200800001E and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the US Government. We thank the Biophysics Resource in the Structural Biophysics Laboratory, NCI at Frederick for use of the LC/ESMS instrument. X-ray diffraction data were collected at the Southeast Regional Collaborative Access Team (SER-CAT) beamline 22-BM of the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at http://www.ser-cat.org/members.html. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract No. W-31-109-Eng-38. NR 48 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Commun. PD JUN PY 2015 VL 71 BP 650 EP 656 DI 10.1107/S2053230X1500504X PN 6 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA CK1SD UT WOS:000355986700003 PM 26057789 ER PT J AU Aschebrook-Kilfoy, B DellaValle, CT Purdue, M Kim, C Zhang, YW Sjodin, A Ward, MH AF Aschebrook-Kilfoy, Briseis DellaValle, Curt T. Purdue, Mark Kim, Christopher Zhang, Yawei Sjodin, Andreas Ward, Mary H. TI Polybrominated Diphenyl Ethers and Thyroid Cancer Risk in the Prostate, Colorectal, Lung, and Ovarian Cancer Screening Trial Cohort SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE brominated diphenyl ethers; flame retardants; thyroid cancer risk ID BROMINATED FLAME RETARDANTS; IN-HOUSE DUST; HORMONE-LEVELS; POLYCHLORINATED-BIPHENYLS; ASSOCIATIONS; PREGNANCY; EXPOSURE; TRENDS; GLAND; SERUM AB Polybrominated diphenyl ethers (PBDEs) alter thyroid hormone homeostasis, but their relationship with thyroid cancer is unknown. To investigate whether serum concentrations of PBDE were associated with thyroid cancer, we conducted a nested, case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter clinical trial in the United States. Cases with thyroid cancer (n = 104) were recruited from 1992 to 2001 and diagnosed through 2009, and controls (n = 208) were individually matched (2: 1) to cases by race, sex, birth date (within 1 year), center, and blood collection date (within 15 days). We used gas chromatography isotope dilution high-resolution mass spectrometry to measure 10 tri-to heptabrominated diphenyl eithers in serum samples. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for lipid-adjusted PBDE levels detected in more than 50% of controls and for the sum of these BDEs (Sigma PBDEs). We observed no significant differences between cases and controls in lipid-adjusted concentrations of Sigma PBDEs (for cases, median = 12.8 ng/g lipid (interquartile range, 6.2-42.1); for controls, median = 19.4 ng/g lipid (interquartile range, 7.6-50.2)) or for individual congeners. Increasing quartiles of Sigma PBDEs and 4 BDE congeners were not associated with risk of thyroid cancer (for the fourth vs. first quartile of Sigma PBDEs, adjusted odd ratio = 0.62, 95% confidence interval: 0.29, 1.30; P for trend = 0.56). Our study does not support an association between exposure to PBDEs and thyroid cancer. C1 [Aschebrook-Kilfoy, Briseis] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA. [Aschebrook-Kilfoy, Briseis; DellaValle, Curt T.; Purdue, Mark; Kim, Christopher; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA. [Zhang, Yawei] Yale Univ, Sch Epidemiol & Publ Hlth, New Haven, CT USA. [Sjodin, Andreas] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Ward, MH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH DHHS, 9609 Med Ctr Dr,6E-138,MSC 9771, Rockville, MD 20850 USA. EM wardm@mail.nih.gov FU Intramural Research Program of the National Cancer Institute, National Institutes of Health FX This work was funded by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 24 TC 2 Z9 2 U1 5 U2 23 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 JUN 1 PY 2015 VL 181 IS 11 BP 883 EP 888 DI 10.1093/aje/kwu358 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CK4GC UT WOS:000356180300007 PM 25939348 ER PT J AU Yang, K Lu, WJ Jia, J Zhang, J Zhao, MM Wang, S Jiang, HY Xu, L Wang, J AF Yang, Kai Lu, Wenju Jia, Jing Zhang, Jie Zhao, Mingming Wang, Sabrina Jiang, Haiyang Xu, Lei Wang, Jian TI Noggin inhibits hypoxia-induced proliferation by targeting store-operated calcium entry and transient receptor potential cation channels SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE noggin; TRPC; store-operated calcium entry; pulmonary hypertension ID ARTERIAL SMOOTH-MUSCLE; BONE-MORPHOGENETIC PROTEIN; MATRIX GLA PROTEIN; PRIMARY PULMONARY-HYPERTENSION; JAK-STAT PATHWAY; CELL-PROLIFERATION; SIGNAL-TRANSDUCTION; ANTAGONIST GREMLIN; INTRACELLULAR CA2+; ENDOTHELIAL-CELLS AB Abnormally elevated bone morphogenetic protein 4 (BMP4) expression and mediated signaling play a critical role in the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH). In this study, we investigated the expression level and functional significance of four reported naturally occurring BMP4 antagonists, noggin, follistatin, gremlin1, and matrix gla protein (MGP), in the lung and distal pulmonary arterial smooth muscle cell (PASMC). A 21-day chronic hypoxic (10% O-2) exposure rat model was utilized, which has been previously shown to successfully establish experimental CHPH. Among the four antagonists, noggin, but not the other three, was selectively downregulated by hypoxic exposure in both the lung tissue and PASMC, in correlation with markedly elevated BMP4 expression, suggesting that the loss of noggin might account for the hypoxiatriggered BMP4 signaling transduction. Then, by using treatment of extrogenous recombinant noggin protein, we further found that noggin significantly normalized 1) BMP4-induced phosphorylation of cellular p38 and ERK1/2; 2) BMP4-induced phosphorylation of cellular JAK2 and STAT3; 3) hypoxia-induced PASMC proliferation; 4) hypoxia-induced store-operated calcium entry (SOCE), and 5) hypoxiaincreased expression of transient receptor potential cation channels (TRPC1 and TRPC6) in PASMC. In combination, these data strongly indicated that the hypoxia-suppressed noggin accounts, at least partially, for hypoxia-induced excessive PASMC proliferation, while restoration of noggin may be an effective way to inhibit cell proliferation by suppressing SOCE and TRPC expression. C1 [Yang, Kai; Lu, Wenju; Jia, Jing; Zhang, Jie; Xu, Lei; Wang, Jian] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Dis, State Key Lab Resp Dis, Guangzhou 510230, Guangdong, Peoples R China. [Yang, Kai; Wang, Sabrina; Jiang, Haiyang; Xu, Lei; Wang, Jian] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. [Zhao, Mingming] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. RP Wang, J (reprint author), Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, 151 Yanjiang Rd, Guangzhou 510230, Guangdong, Peoples R China. EM wlu92@yahoo.com; jwang31@jhmi.edu FU National Institutes of Health (National Heart, Lung, and Blood Institute) [R01 HL-093020]; National Natural Science Foundation of China [81173112, 81470246, 81170052, 81220108001]; Guangzhou Department of Education Yangcheng Scholarship [12A001S]; Guangzhou Department of Natural Science [2014Y2-00167]; Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme; China Scholarship Council [201208440091] FX This work was supported by National Institutes of Health (National Heart, Lung, and Blood Institute Grant R01 HL-093020), National Natural Science Foundation of China (81173112, 81470246, 81170052, 81220108001), Guangzhou Department of Education Yangcheng Scholarship (12A001S), Guangzhou Department of Natural Science (2014Y2-00167) and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2014, W. Lu), and China Scholarship Council (201208440091 for K. Yang). NR 50 TC 3 Z9 3 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN 1 PY 2015 VL 308 IS 11 BP C869 EP C878 DI 10.1152/ajpcell.00349.2014 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA CK5CO UT WOS:000356240000003 PM 25740156 ER PT J AU Nayyar, GML Breman, JG Herrington, JE AF Nayyar, Gaurvika M. L. Breman, Joel G. Herrington, James E. TI The Global Pandemic of Falsified Medicines: Laboratory and Field Innovations and Policy Perspectives: Summary SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material ID SUB-SAHARAN AFRICA; SUBSTANDARD ANTIMALARIALS; SOUTHEAST-ASIA; QUALITY; ANTIBIOTICS; HEALTH; DRUGS C1 [Nayyar, Gaurvika M. L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Nayyar, Gaurvika M. L.] Johns Hopkins Carey Business Sch, Baltimore, MD USA. [Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Herrington, James E.] Univ N Carolina, Gillings Sch Global Publ Hlth, Gillings Global Gateway, Chapel Hill, NC 27599 USA. RP Herrington, JE (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Gillings Global Gateway, 135 Dauer Dr,104 Rosenau Hall, Chapel Hill, NC 27599 USA. EM gaurvika@gmail.com; jbreman@nih.gov; jim.herrington@unc.edu NR 34 TC 6 Z9 6 U1 1 U2 9 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 2015 VL 92 IS 6 SU S BP 2 EP 7 DI 10.4269/ajtmh.15-0221 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CJ8XA UT WOS:000355785600002 PM 25897072 ER PT J AU Nayyar, GML Attaran, A Clark, JP Culzoni, MJ Fernandez, FM Herrington, JE Kendall, M Newton, PN Breman, JG AF Nayyar, Gaurvika M. L. Attaran, Amir Clark, John P. Culzoni, M. Julia Fernandez, Facundo M. Herrington, James E. Kendall, Megan Newton, Paul N. Breman, Joel G. TI Responding to the Pandemic of Falsified Medicines SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID GLOBAL HEALTH; COUNTERFEIT; GOVERNANCE AB Over the past decade, the number of countries reporting falsified (fake, spurious/falsely labeled/counterfeit) medicines and the types and quantities of fraudulent drugs being distributed have increased greatly. The obstacles in combating falsified pharmaceuticals include 1) lack of consensus on definitions, 2) paucity of reliable and scalable technology to detect fakes before they reach patients, 3) poor global and national leadership and accountability systems for combating this scourge, and 4) deficient manufacturing and regulatory challenges, especially in China and India where fake products often originate. The major needs to improve the quality of the world's medicines fall into three main areas: 1) research to develop and compare accurate and affordable tools to identify high-quality drugs at all levels of distribution; 2) an international convention and national legislation to facilitate production and utilization of high-quality drugs and protect all countries from the criminal and the negligent who make, distribute, and sell life-threatening products; and 3) a highly qualified, well-supported international science and public health organization that will establish standards, drug-quality surveillance, and training programs like the U.S. Food and Drug Administration. Such leadership would give authoritative guidance for countries in cooperation with national medical regulatory agencies, pharmaceutical companies, and international agencies, all of which have an urgent interest and investment in ensuring that patients throughout the world have access to good quality medicines. The organization would also advocate strongly for including targets for achieving good quality medicines in the United Nations Millennium Development Goals and Sustainable Development Goals. C1 [Nayyar, Gaurvika M. L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Nayyar, Gaurvika M. L.] Johns Hopkins Carey Business Sch, Baltimore, MD USA. [Attaran, Amir] Univ Ottawa, Populat Hlth & Global Dev Policy, Ottawa, ON, Canada. [Clark, John P.] Pfizer Global Secur, Pfizer Pharmaceut, New York, NY USA. [Culzoni, M. Julia; Fernandez, Facundo M.] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA. [Herrington, James E.] Univ N Carolina, Gillings Global Gateway, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Kendall, Megan] Univ Ottawa, Sch Law, Ottawa, ON, Canada. [Newton, Paul N.] Mahosot Hosp, Lao Oxford Mahosot Hosp Wellcome Trust Res Unit, Microbiol Lab, Viangchan, Laos. [Newton, Paul N.] Univ Oxford, Nuffield Dept Med, Ctr Trop Med, Churchill Hosp, Oxford, England. [Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM gaurvika@gmail.com; aattaran@uottawa.ca; john.clark@pfizer.com; jculzoni3@mail.gatech.edu; femandez@chemistry.gatech.edu; jim.herrington@unc.edu; megan_kendall@hotmail.com; paul@tropmedres.ac; jbreman@nih.gov OI Clark, Jocalyn/0000-0002-8014-3989 FU Fogarty International Center, National Institutes of Health; Wellcome Trust of Great Britain FX This study was funded by the Fogarty International Center, National Institutes of Health. Paul N. Newton is supported by the Wellcome Trust of Great Britain. NR 39 TC 3 Z9 3 U1 3 U2 11 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 2015 VL 92 IS 6 SU S BP 113 EP 118 DI 10.4269/ajtmh.14-0393 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CJ8XA UT WOS:000355785600015 PM 25897060 ER PT J AU Hong, CS Ho, W Zhang, C Yang, CZ Elder, JB Zhuang, ZP AF Hong, Christopher S. Ho, Winson Zhang, Chao Yang, Chunzhang Elder, J. Bradley Zhuang, Zhengping TI LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential SO CANCER BIOLOGY & THERAPY LA English DT Review DE cell cycle; chemosensitization; mitotic catastrophe; protein phosphatase 2A; small molecule inhibitor; radiosensitizationreview ID PROTEIN PHOSPHATASE 2A; SOFT-TISSUE SARCOMAS; SYNTHETIC CANTHARIDIN ANALOG; WNT/BETA-CATENIN PATHWAY; METASTATIC BREAST-CANCER; BLOOD-BRAIN-BARRIER; CELL-LINE PANC-1; A-ALPHA SUBUNIT; PANCREATIC-CANCER; DNA-DAMAGE AB Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that plays a significant role in mitotic progression and cellular responses to DNA damage. While traditionally viewed as a tumor suppressor, inhibition of PP2A has recently come to attention as a novel therapeutic means of driving senescent cancer cells into mitosis and promoting cell death via mitotic catastrophe. These findings have been corroborated in numerous studies utilizing naturally produced compounds that selectively inhibit PP2A. To overcome the known human toxicities associated with these compounds, a water-soluble small molecule inhibitor, LB100, was recently developed to competitively inhibit the PP2A protein. This review summarizes the pre-clinical studies to date that have demonstrated the anti-cancer activity of LB100 via its chemo- and radio-sensitizing properties. These studies demonstrate the tremendous therapeutic potential of LB100 in a variety of cancer types. The results of an ongoing phase 1 trial are eagerly anticipated. C1 [Hong, Christopher S.; Elder, J. Bradley] Ohio State Univ, Wexner Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. [Hong, Christopher S.; Ho, Winson; Zhang, Chao; Yang, Chunzhang; Zhuang, Zhengping] NINDS, NIH, Surg Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), NINDS, NIH, Surg Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH). NR 152 TC 6 Z9 6 U1 7 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUN PY 2015 VL 16 IS 6 BP 821 EP 833 DI 10.1080/15384047.2015.1040961 PG 13 WC Oncology SC Oncology GA CK5XT UT WOS:000356302100002 PM 25897893 ER PT J AU Hatch, M Ostroumova, E Brenner, A Federenko, Z Gorokh, Y Zvinchuk, O Shpak, V Tereschenko, V Tronko, M Mabuchi, K AF Hatch, M. Ostroumova, E. Brenner, A. Federenko, Z. Gorokh, Y. Zvinchuk, O. Shpak, V. Tereschenko, V. Tronko, M. Mabuchi, K. TI Non-thyroid cancer in Northern Ukraine in the post-Chernobyl period: Short report SO CANCER EPIDEMIOLOGY LA English DT Article DE Ionizing radiation; Chernobyl accident; Cancer incidence; Standardized incidence ratio; Ecological study ID RADIATION-INDUCED LEUKEMIA; IN-UTERO EXPOSURE; INFANT LEUKEMIA; CHILDHOOD LEUKEMIA; THYROID-DISEASES; ACCIDENT; EUROPE; POPULATION; BYELARUS; COHORT AB The Chernobyl nuclear power plant accident in Ukraine in 1986 led to widespread radioactive releases into the environment - primarily of radioiodines and cesium - heavily affecting the northern portions of the country, with settlement-averaged thyroid doses estimated to range from 10 mGy to more than 10 Gy. The increased risk of thyroid cancer among exposed children and adolescents is well established but the impact of radioactive contamination on the risk of other types of cancer is much less certain. To provide data on a public health issue of major importance, we have analyzed the incidence of nonthyroid cancers during the post-Chernobyl period in a well-defined cohort of 13,203 individuals who were < 18 years of age at the time of the accident. The report is based on standardized incidence ratio (SIR) analysis of 43 non-thyroid cancers identified through linkage with the National Cancer Registry of Ukraine for the period 1998 through 2009. We compared the observed and expected number of cases in three cancer groupings: all solid cancers excluding thyroid, leukemia, and lymphoma. Our analyses found no evidence of a statistically significant elevation in cancer risks in this cohort exposed at radiosensitive ages, although the cancer trends, particularly for leukemia (SIR = 1.92, 95% confidence interval: 0.69; 4.13), should continue to be monitored. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Hatch, M.; Ostroumova, E.; Brenner, A.; Mabuchi, K.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zvinchuk, O.; Shpak, V.; Tereschenko, V.; Tronko, M.] Inst Endocrinol & Metab, Kiev, Ukraine. [Federenko, Z.; Gorokh, Y.] Natl Canc Inst, Natl Canc Registry Ukraine, Kiev, Ukraine. RP Hatch, M (reprint author), NCI, Radiat Epidemiol Branch, 9609 Med Ctr, Bethesda, MD 20892 USA. EM hatchm@mail.nih.gov OI Zvinchuk, Alexander/0000-0001-7163-1932 FU Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This research was supported by the Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. We wish to acknowledge the critical role of the late Dr. Geoffrey Howe in establishing the Ukraine National Cancer Registry and in developing procedures for record linkage. NR 20 TC 2 Z9 4 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 EI 1877-783X J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD JUN PY 2015 VL 39 IS 3 BP 279 EP 283 DI 10.1016/j.canep.2015.02.002 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CJ9LA UT WOS:000355822600003 PM 25794878 ER PT J AU Sholler, GLS Bond, JP Bergendahl, G Dutta, A Dragon, J Neville, K Ferguson, W Roberts, W Eslin, D Kraveka, J Kaplan, J Mitchell, D Parikh, N Merchant, M Ashikaga, T Hanna, G Lescault, PJ Siniard, A Corneveaux, J Huentelman, M Trent, J AF Sholler, Giselle L. Saulnier Bond, Jeffrey P. Bergendahl, Genevieve Dutta, Akshita Dragon, Julie Neville, Kathleen Ferguson, William Roberts, William Eslin, Don Kraveka, Jacqueline Kaplan, Joel Mitchell, Deanna Parikh, Nehal Merchant, Melinda Ashikaga, Takamaru Hanna, Gina Lescault, Pamela Jean Siniard, Ashley Corneveaux, Jason Huentelman, Matthew Trent, Jeffrey TI Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma SO CANCER MEDICINE LA English DT Article DE Genomic profiling; molecular-guided therapy; molecular tumor board; neuroblastoma; pediatric oncology ID HIGH-RISK NEUROBLASTOMA; PHASE-I; SOLID TUMORS; PEDIATRIC-PATIENTS; MULTIVARIATE-ANALYSIS; DRUG TARGETS; CANCERS; RECURRENT; GENES; TRANSPLANTATION AB The primary objective of the study was to evaluate the feasibility and safety of a process which would utilize genome-wide expression data from tumor biopsies to support individualized treatment decisions. Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%. Molecular profiling may provide data which will enable the practitioner to select the most appropriate therapeutic option for individual patients, thus improving outcomes. Sixteen patients with neuroblastoma were enrolled of which fourteen were eligible for this study. Feasibility was defined as completion of tumor biopsy, pathological evaluation, RNA quality control, gene expression profiling, bioinformatics analysis, generation of a drug prediction report, molecular tumor board yielding a treatment plan, independent medical monitor review, and treatment initiation within a 21day period. All eligible biopsies passed histopathology and RNA quality control. Expression profiling by microarray and RNA sequencing were mutually validated. The average time from biopsy to report generation was 5.9days and from biopsy to initiation of treatment was 12.4days. No serious adverse events were observed and all adverse events were expected. Clinical benefit was seen in 64% of patients as stabilization of disease for at least one cycle of therapy or partial response. The overall response rate was 7% and the progression free survival was 59days. This study demonstrates the feasibility and safety of performing real-time genomic profiling to guide treatment decision making for pediatric neuroblastoma patients. C1 [Sholler, Giselle L. Saulnier; Bergendahl, Genevieve; Dutta, Akshita; Mitchell, Deanna] Helen DeVos Childrens Hosp, Grand Rapids, MI 49503 USA. [Sholler, Giselle L. Saulnier] Michigan State Univ, Coll Med, Grand Rapids, MI USA. [Bond, Jeffrey P.; Dragon, Julie] Univ Vermont, Dept Microbiol & Mol Genet, Coll Med, Burlington, VT 05405 USA. [Neville, Kathleen] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Ferguson, William] St Louis Univ, Cardinal Glennon Childrens Hosp, St Louis, MO USA. [Roberts, William] Univ Calif San Diego, Sch Med, San Diego, CA USA. [Roberts, William] Rady Childrens Hosp, San Diego, CA USA. [Eslin, Don; Hanna, Gina] Arnold Palmer Hosp Children, Orlando, FL USA. [Kraveka, Jacqueline] Med Univ S Carolina, Charleston, SC 29425 USA. [Kaplan, Joel] Levine Childrens Hosp, Charlotte, NC USA. [Parikh, Nehal] Connecticut Childrens Med Ctr, Hartford, CT USA. [Merchant, Melinda] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Ashikaga, Takamaru] Univ Vermont, Coll Med, Med Biostat, Burlington, VT USA. [Lescault, Pamela Jean] Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Marine Biol Lab, Woods Hole, MA USA. [Siniard, Ashley; Corneveaux, Jason; Huentelman, Matthew; Trent, Jeffrey] Translat Genom Res Inst, Phoenix, AZ USA. RP Sholler, GLS (reprint author), 100 Michigan Ave NE MC 272, Grand Rapids, MI 49503 USA. EM Giselle.SaulnierSholler@helendevoschildrens.org FU Dell Corporation; Beat NB; Arms Wide Open Foundation; Charles and Meryl Witmer Foundation; Owen Moscone Foundation; Because of Ezra Foundation; Max's Ring of Fire, Lillie's Friends Foundation; Brooke's Blossoming Hope Foundation; Melina's White Light; Ishan Gala Foundation; Ethan's Rodeo; Daxton's Fish FX We thank the Dell Corporation for their grant support for this clinical trial and their computational expertise. We thank Maja Sholler for her support in editing of this manuscript. We would also like to thank the pediatric advocate foundations supporting our work to advance science including Beat NB, Arms Wide Open Foundation, Charles and Meryl Witmer Foundation, Owen Moscone Foundation, Because of Ezra Foundation, Max's Ring of Fire, Lillie's Friends Foundation, Brooke's Blossoming Hope Foundation, Melina's White Light, Ishan Gala Foundation, Ethan's Rodeo, Daxton's Fish. NR 43 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD JUN PY 2015 VL 4 IS 6 BP 871 EP 886 DI 10.1002/cam4.436 PG 16 WC Oncology SC Oncology GA CK1SQ UT WOS:000355988000010 ER PT J AU Iwakawa, R Kohno, T Totoki, Y Shibata, T Tsuchihara, K Mimaki, S Tsuta, K Narita, Y Nishikawa, R Noguchi, M Harris, CC Robles, AI Yamaguchi, R Imoto, S Miyano, S Totsuka, H Yoshida, T Yokota, J AF Iwakawa, Reika Kohno, Takashi Totoki, Yasushi Shibata, Tatsuhiro Tsuchihara, Katsuya Mimaki, Sachiyo Tsuta, Koji Narita, Yoshitaka Nishikawa, Ryo Noguchi, Masayuki Harris, Curtis C. Robles, Ana I. Yamaguchi, Rui Imoto, Seiya Miyano, Satoru Totsuka, Hirohiko Yoshida, Teruhiko Yokota, Jun TI Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing SO CARCINOGENESIS LA English DT Article ID GENOMIC ANALYSIS; IDENTIFICATION; FRAMEWORK; HETEROGENEITY; METASTASES; EVOLUTION; TUMOR AB Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. Only 15% of SCLC patients survive beyond 2 years after diagnosis. Therefore, for the improvement of patients' outcome in this disease, it is necessary to identify genetic alterations applicable as therapeutic targets in SCLC cells. The purpose of this study is the identification of genes frequently mutated and expressed in SCLCs that will be targetable for therapy of SCLC patients. Exome sequencing was performed in 28 primary tumors and 16 metastatic tumors from 38 patients with SCLCs. Expression of mutant alleles was verified in 19 cases by RNA sequencing. TP53, RB1 and PTEN were identified as being significantly mutated genes. Additional 36 genes were identified as being frequently (>= 10%) mutated in SCLCs by combining the results of this study and two recent studies. Mutated alleles were expressed in 8 of the 36 genes, TMEM132D, SPTA1, VPS13B, CSMD2, ANK2, ASTN1, ASPM and FBN3. In particular, the TMEM132D, SPTA1 and VPS13B genes were commonly mutated in both early and late stage tumors, primary tumors and metastases, and tumors before and after chemotherapy, as in the case of the TP53 and RB1 genes. Therefore, in addition to TP53, RB1 and PTEN, TMEM132D, SPTA1 and VPS13B could be also involved in SCLC development, with the products from their mutated alleles being potential therapeutic targets in SCLC patients. C1 [Iwakawa, Reika; Kohno, Takashi; Yokota, Jun] Natl Canc Ctr, Res Inst, Div Genome Biol, Tokyo 1040045, Japan. [Kohno, Takashi; Tsuchihara, Katsuya; Mimaki, Sachiyo] Natl Canc Ctr, Div Translat Res, Exploratory Oncol Res & Clin Trial Ctr, Tokyo 1040045, Japan. [Totoki, Yasushi; Shibata, Tatsuhiro] Natl Canc Ctr, Res Inst, Div Canc Genom, Tokyo 1040045, Japan. [Tsuta, Koji] Natl Canc Ctr, Pathol Div, Tokyo 1040045, Japan. [Narita, Yoshitaka] Natl Canc Ctr, Dept Neurosurg & Neurooncol, Tokyo 1040045, Japan. [Nishikawa, Ryo] Saitama Med Univ, Dept Neurooncol Neurosurg, Int Med Ctr, Saitama 3501298, Japan. [Noguchi, Masayuki] Univ Tsukuba, Dept Pathol, Fac Med, Ibaraki 3058575, Japan. [Harris, Curtis C.; Robles, Ana I.] NCI, Lab Human Carcinogenesis, NIH, Bethesda, MD 20892 USA. [Yamaguchi, Rui; Imoto, Seiya; Miyano, Satoru] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Tokyo 1088639, Japan. [Totsuka, Hirohiko] Hitachi Govt & Publ Corp Syst Engn Ltd, Solut Div 4, Ctr Res & Dev, Bioinfomat Grp, Tokyo 1358633, Japan. [Yoshida, Teruhiko] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 1040045, Japan. [Yokota, Jun] Inst Predict & Personalized Med Canc, Canc Genome Biol Grp, Barcelona 08916, Spain. RP Yokota, J (reprint author), Natl Canc Ctr, Res Inst, Div Genome Biol, Chuo Ku, Tsukiji 5-1-1, Tokyo 1040045, Japan. EM jyokota@ncc.go.jp FU Ministry of Health, Labor, and Welfare, Japan [H26-practical-general-007/094]; ISIS grant (Institute of Health Carlos III) in Spain [IIS13/00849]; FIS grant (Institute of Health Carlos III) in Spain [PI13/00849]; European Regional Development Funds (FEDER) of the European Union FX Ministry of Health, Labor, and Welfare, Japan, for Practical Research for Innovative Cancer Control (H26-practical-general-007/094); ISIS (IIS13/00849) and FIS (PI13/00849) grants (Institute of Health Carlos III) in Spain, co-financed by the European Regional Development Funds (FEDER) of the European Union. NR 23 TC 15 Z9 15 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2015 VL 36 IS 6 BP 616 EP 621 DI 10.1093/carcin/bgv026 PG 6 WC Oncology SC Oncology GA CK4GK UT WOS:000356181700002 PM 25863124 ER PT J AU Shastri, N Yewdell, JW AF Shastri, Nilabh Yewdell, Jonathan W. TI Editorial overview: Antigen processing and presentation: Where cellular immunity begins SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material ID TRANSLATION; GENERATION C1 [Shastri, Nilabh] Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol & Pathogenesis, Berkeley, CA 94720 USA. [Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Shastri, N (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol & Pathogenesis, 229 Stanley Hall, Berkeley, CA 94720 USA. EM nshastri@berkeley.edu; JYEWDELL@nih.gov FU Intramural NIH HHS NR 6 TC 0 Z9 0 U1 1 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2015 VL 34 BP V EP VII DI 10.1016/j.coi.2015.04.004 PG 3 WC Immunology SC Immunology GA CK3NH UT WOS:000356122300001 PM 25964203 ER PT J AU Mittal, SK Roche, PA AF Mittal, Sharad K. Roche, Paul A. TI Suppression of antigen presentation by IL-10 SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MHC CLASS-II; DENDRITIC CELLS; ANTIINFLAMMATORY RESPONSE; TYROSINE PHOSPHORYLATION; NEGATIVE REGULATION; PEPTIDE COMPLEXES; INTERFERON-GAMMA; INDUCED GENES; B-CELLS; INTERLEUKIN-10 AB Regulated antigen presentation to immune cells determines the effectiveness of an immune response. IL-10 is an immunosuppressive cytokine that regulates immune responses by inhibiting the ability of APCs to present antigens to T cells in a variety of ways. The mechanisms of IL-10-mediated immunosuppression include interference in TLR-mediated or IFN gamma-mediated dendritic cell (DC) and macrophage activation as well as direct induction of genes that suppress APC function. In this review we will discuss current studies exploring the molecular mechanisms by which IL-10 suppresses APC function. C1 [Mittal, Sharad K.; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM paul.roche@nih.gov FU Intramural Research Program of the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institutes of Health. NR 48 TC 19 Z9 21 U1 2 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2015 VL 34 BP 22 EP 27 DI 10.1016/j.coi.2014.12.009 PG 6 WC Immunology SC Immunology GA CK3NH UT WOS:000356122300006 PM 25597442 ER PT J AU Fukushima, M Chao, ZC Fujii, N AF Fukushima, Makoto Chao, Zenas C. Fujii, Naotaka TI Studying brain functions with mesoscopic measurements: Advances in electrocorticography for non-human primates SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID CORTICAL-NEURONS; ELECTRODE ARRAY; VISUAL-CORTEX; MONKEYS; FIELDS; AREAS; ATTENTION; MACAQUE; ECOG AB Our brain is organized in a modular structure. Information in different modalities is processed within distinct cortical areas. However, individual cortical areas cannot enable complex cognitive functions without interacting with other cortical areas. Electrocorticography (ECoG) has recently become an important tool for studying global network activity across cortical areas in animal models. With stable recordings of electrical field potentials from multiple cortical areas, ECoG provides an opportunity to systematically study large-scale cortical activity at a mesoscopic spatiotemporal resolution under various experimental conditions. Recent developments in thin, flexible ECoG electrodes permit recording field potentials from not only gyral but intrasulcal cortical surfaces. Our review here focuses on the recent advances of ECoG applications to non-human primates. C1 [Fukushima, Makoto] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Chao, Zenas C.; Fujii, Naotaka] RIKEN, Brain Sci Inst, Lab Adapt Intelligence, Wako, Saitama 3510198, Japan. RP Fujii, N (reprint author), RIKEN, Brain Sci Inst, Lab Adapt Intelligence, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. EM na@brain.riken.jp OI Fukushima, Makoto/0000-0002-8809-7892 FU Ministry of Education, Culture, Sports, Science and Technology of Japan [23118003]; Intramural Research Program of the National Institute of Mental Health (NIMH), NIH, DHHS FX This work was supported by Grant-in-Aid for Scientific Research on Innovative Areas (23118003; Adolescent Mind & Self-Regulation) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Intramural Research Program of the National Institute of Mental Health (NIMH), NIH, DHHS. M.F. thanks Mortimer Mishkin for support, and Bruno Averbeck and Richard Saunders for comments on the manuscript. NR 55 TC 2 Z9 2 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD JUN PY 2015 VL 32 BP 124 EP 131 DI 10.1016/j.conb.2015.03.015 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CK4MW UT WOS:000356198900017 PM 25889531 ER PT J AU Jarcho, JM Romer, AL Shechner, T Galvan, A Guyer, AE Leibenluft, E Pine, DS Nelson, EE AF Jarcho, Johanna M. Romer, Adrienne L. Shechner, Tomer Galvan, Adriana Guyer, Amanda E. Leibenluft, Ellen Pine, Daniel S. Nelson, Eric E. TI Forgetting the best when predicting the worst: Preliminary observations on neural circuit function in adolescent social anxiety SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Development; Striatum; Medial prefrontal cortex; Prediction error; Peer feedback; Learning ID OBSESSIVE-COMPULSIVE DISORDER; ANTICIPATED PEER EVALUATION; PSYCHOPHYSIOLOGICAL INTERACTIONS; PREFRONTAL CORTEX; AMYGDALA SENSITIVITY; PUBERTAL DEVELOPMENT; SELF-EVALUATIONS; FEAR EXTINCTION; HUMAN STRIATUM; REWARD AB Social anxiety disorder typically begins in adolescence, a sensitive period for brain development, when increased complexity and salience of peer relationships requires novel forms of social learning. Disordered social learning in adolescence may explain how brain dysfunction promotes social anxiety. Socially anxious adolescents (n = 15) and adults (n = 19) and non-anxious adolescents (n = 24) and adults (n = 32) predicted, then received, social feedback from high and low-value peers while undergoing functional magnetic resonance imaging (fMRI). A surprise recall task assessed memory biases for feedback. Neural correlates of social evaluation prediction errors (PEs) were assessed by comparing engagement to expected and unexpected positive and negative feedback. For socially anxious adolescents, but not adults or healthy participants of either age group, PEs elicited heightened striatal activity and negative fronto-striatal functional connectivity. This occurred selectively to unexpected positive feedback from high-value peers and corresponded with impaired memory for social feedback. While impaired memory also occurred in socially-anxious adults, this impairment was unrelated to brain-based PE activity. Thus, social anxiety in adolescence may relate to altered neural correlates of PEs that contribute to impaired learning about social feedback. Small samples necessitate replication. Nevertheless, results suggest that the relationship between learning and fronto-striatal function may attenuate as development progresses. Published by Elsevier Ltd. C1 [Jarcho, Johanna M.; Pine, Daniel S.; Nelson, Eric E.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Romer, Adrienne L.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27706 USA. [Shechner, Tomer] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel. [Galvan, Adriana] Univ Los Angeles, Dept Psychol, Los Angeles, CA USA. [Guyer, Amanda E.] Univ Davis, Ctr Mind & Brain, Dept Human Ecol, Davis, CA USA. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA. RP Jarcho, JM (reprint author), NIMH, Sect Dev & Affect Neurosci, 9000 Rockville Pike MSC 2670,Bldg 15K,Rm 201, Bethesda, MD 20892 USA. EM johanna.jarcho@nih.gov OI Nelson, Eric/0000-0002-3376-2453; Jarcho, Johanna/0000-0001-9075-6968 FU NIMH intramural research program [00018057, 01-M-0192] FX This research (NCT# 00018057; Protocol ID 01-M-0192) was supported by the NIMH intramural research program. NR 71 TC 6 Z9 6 U1 4 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1878-9293 EI 1878-9307 J9 DEV COGN NEUROS-NETH JI Dev. Cogn. Neurosci. PD JUN PY 2015 VL 13 BP 21 EP 31 DI 10.1016/j.dcn.205.03.002 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CK2PK UT WOS:000356052800003 PM 25933410 ER PT J AU Luis, AD Douglass, RJ Mills, JN Bjornstad, ON AF Luis, Angela D. Douglass, Richard J. Mills, James N. Bjornstad, Ottar N. TI Environmental fluctuations lead to predictability in Sin Nombre hantavirus outbreaks SO ECOLOGY LA English DT Article DE critical host density; deer mice; delayed density dependence; ecological cascade; ecological forecasting; Peromyscus maniculatus; Sin Nombre virus; zoonoses ID SOUTHWESTERN UNITED-STATES; DENSITY-DEPENDENT PREVALENCE; MICE PEROMYSCUS-MANICULATUS; MONTANA DEER MICE; LONG-TERM; RESERVOIR POPULATIONS; RODENT POPULATIONS; PULMONARY SYNDROME; VIRUS-INFECTION; DISEASE RISK AB Predicting outbreaks of zoonotic infections in reservoir hosts that live in highly fluctuating environments, such as Sin Nombre virus (SNV) in deer mice, is particularly challenging because host populations vary widely in response to environmental conditions and the relationship between field infection rates and abundance often appears to contradict conventional theory. Using a stage-structured host-pathogen model parameterized and cross-validated from a unique 15-year data set, we show how stochastic population fluctuations can lead to predictable dynamics of SNV in deer mice. Significant variation in host abundance and the basic reproductive number of the virus results in intermittent crossing of the critical host population density necessary for SNV endemicity and frequent local extinctions. When environmental conditions favor growth of the host population above the threshold, host-pathogen interactions lead to delayed density dependence in reservoir prevalence. The resultant ecological delay may provide a neglected opportunity for outbreak prediction in zoonoses. C1 [Luis, Angela D.; Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. [Luis, Angela D.] Univ Montana, Dept Ecosyst & Conservat Sci, Missoula, MT 59812 USA. [Luis, Angela D.; Bjornstad, Ottar N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Douglass, Richard J.] Univ Montana, Montana Tech, Dept Biol, Butte, MT 59701 USA. [Mills, James N.] Emory Univ, Populat Biol Ecol & Evolut Program, Atlanta, GA 30322 USA. RP Luis, AD (reprint author), Univ Montana, Dept Ecosyst & Conservat Sci, Missoula, MT 59812 USA. EM Angela.Luis@umontana.edu FU U.S. NIH from the INBRE BRIN program [P20RR16455-05]; U.S. CDC [US3/CCU813599]; Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate (Department of Homeland Security); Fogarty International Center (NIH) FX We thank Dave Cameron and Dana Ranch, Inc., and the Confederated Salish and Kootenai Tribes at Polson for unlimited access to their properties, as well as Kent Wagoner for database management and design of specialty software. Scott Carver, Kevin Hughes, Arlene Alvarado, Farrah Arneson, Karoun Bagamian, Jessica Bertoglio, Brent Lonner, Jonnae Lumsden, Bill Semmons, and Amy Skypala provided valuable assistance in the field. S. Zanto provided serologic testing at the Montana State Department of Public Health and Human Services Laboratory; P. Rollin and A. Comer arranged serologic testing at the Special Pathogens Branch Laboratory, U.S. Centers for Disease Control and Prevention. Financial support was provided by the U.S. NIH grant P20RR16455-05 from the INBRE BRIN program, the U.S. CDC through cooperative agreement US3/CCU813599, and the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate (Department of Homeland Security) and the Fogarty International Center (NIH). NR 47 TC 3 Z9 3 U1 6 U2 38 PU ECOLOGICAL SOC AMER PI WASHINGTON PA 1990 M STREET NW, STE 700, WASHINGTON, DC 20036 USA SN 0012-9658 EI 1939-9170 J9 ECOLOGY JI Ecology PD JUN PY 2015 VL 96 IS 6 BP 1691 EP 1701 DI 10.1890/14-1910.1 PG 11 WC Ecology SC Environmental Sciences & Ecology GA CK2DV UT WOS:000356021700024 ER PT J AU White, K Lu, Y Annis, S Hale, AE Chau, BN Dahlman, JE Hemann, C Opotowsky, AR Vargas, SO Rosas, I Perrella, MA Osorio, JC Haley, KJ Graham, BB Kumar, R Saggar, R Saggar, R Wallace, WD Ross, DJ Khan, OF Bader, A Gochuico, BR Matar, M Polach, K Johannessen, NM Prosser, HM Anderson, DG Langer, R Zweier, JL Bindoff, LA Systrom, D Waxman, AB Jin, RC Chan, SY AF White, Kevin Lu, Yu Annis, Sofia Hale, Andrew E. Chau, B. Nelson Dahlman, James E. Hemann, Craig Opotowsky, Alexander R. Vargas, Sara O. Rosas, Ivan Perrella, Mark A. Osorio, Juan C. Haley, Kathleen J. Graham, Brian B. Kumar, Rahul Saggar, Rajan Saggar, Rajeev Wallace, W. Dean Ross, David J. Khan, Omar F. Bader, Andrew Gochuico, Bernadette R. Matar, Majed Polach, Kevin Johannessen, Nicolai M. Prosser, Haydn M. Anderson, Daniel G. Langer, Robert Zweier, Jay L. Bindoff, Laurence A. Systrom, David Waxman, Aaron B. Jin, Richard C. Chan, Stephen Y. TI Genetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron-sulfur deficiency and pulmonary hypertension SO EMBO MOLECULAR MEDICINE LA English DT Article DE endothelial; iron-sulfur; metabolism; microRNA; mitochondria ID ARTERIAL-HYPERTENSION; ENDOTHELIAL-CELLS; MITOCHONDRIAL DISEASE; EXERCISE; LUNG; METABOLISM; PROTEINS; MYOPATHY; CLUSTERS; MUTATION AB Iron-sulfur (Fe-S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR-210-ISCU1/2 axis cause Fe-S deficiencies in vivo and promote PH. In pulmonary vascular cells and particularly endothelium, hypoxic induction of miR-210 and repression of the miR-210 targets ISCU1/2 down-regulated Fe-S levels. In mouse and human vascular and endothelial tissue affected by PH, miR-210 was elevated accompanied by decreased ISCU1/2 and Fe-S integrity. In mice, miR-210 repressed ISCU1/2 and promoted PH. Mice deficient in miR-210, via genetic/pharmacologic means or via an endothelial-specific manner, displayed increased ISCU1/2 and were resistant to Fe-S-dependent pathophenotypes and PH. Similar to hypoxia or miR-210 overexpression, ISCU1/2 knockdown also promoted PH. Finally, cardiopulmonary exercise testing of a woman with homozygous ISCU mutations revealed exercise-induced pulmonary vascular dysfunction. Thus, driven by acquired (hypoxia) or genetic causes, the miR-210-ISCU1/2 regulatory axis is a pathogenic lynchpin causing Fe-S deficiency and PH. These findings carry broad translational implications for defining the metabolic origins of PH and potentially other metabolic diseases sharing similar underpinnings. C1 [White, Kevin; Lu, Yu; Annis, Sofia; Hale, Andrew E.; Opotowsky, Alexander R.; Jin, Richard C.; Chan, Stephen Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Chau, B. Nelson] Regulus Therapeut, San Diego, CA USA. [Dahlman, James E.; Bader, Andrew; Anderson, Daniel G.; Langer, Robert] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Dahlman, James E.; Bader, Andrew; Anderson, Daniel G.; Langer, Robert] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Dahlman, James E.; Khan, Omar F.; Anderson, Daniel G.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Dahlman, James E.; Khan, Omar F.; Anderson, Daniel G.; Langer, Robert] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Hemann, Craig; Zweier, Jay L.] Ohio State Univ, Dept Internal Med, Wexner Med Ctr, Davis Heart & Lung Res Inst,Div Cardiovasc Med, Columbus, OH 43210 USA. [Opotowsky, Alexander R.] Boston Univ, Sch Med, Boston Childrens Hosp, Dept Cardiol, Boston, MA 02118 USA. [Vargas, Sara O.] Boston Univ, Sch Med, Boston Childrens Hosp, Dept Pathol, Boston, MA 02118 USA. [Rosas, Ivan; Perrella, Mark A.; Osorio, Juan C.; Haley, Kathleen J.; Systrom, David; Waxman, Aaron B.] Harvard Univ, Sch Med, Dept Med, Div Pulm Crit Care Med, Boston, MA USA. [Perrella, Mark A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pediat Newborn Med, Boston, MA 02115 USA. [Graham, Brian B.; Kumar, Rahul] Univ Colorado, Program Translat Lung Res, Denver, CO 80202 USA. [Saggar, Rajan; Wallace, W. Dean; Ross, David J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Saggar, Rajan; Wallace, W. Dean; Ross, David J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Saggar, Rajeev] Univ Arizona, Coll Med, Dept Cardiothorac Surg, Phoenix, AZ USA. [Gochuico, Bernadette R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Matar, Majed; Polach, Kevin] Cels EGEN Inc, Huntsville, AL USA. [Johannessen, Nicolai M.] Univ Bergen, Dept Cardiol, Bergen, Norway. [Prosser, Haydn M.] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Cambridge, England. [Bindoff, Laurence A.] Univ Bergen, Dept Clin Med, Bergen, Norway. [Bindoff, Laurence A.] Haukeland Hosp, Dept Neurol, N-5021 Bergen, Norway. [White, Kevin; Lu, Yu; Annis, Sofia; Hale, Andrew E.; Opotowsky, Alexander R.; Jin, Richard C.; Chan, Stephen Y.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Network Med, Boston, MA 02115 USA. RP Chan, SY (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. EM sychan@partners.org OI Hemann, Craig/0000-0002-7380-4072 FU NIH [K08HL096834, U54-CA151884, R01-DE016516-06, EB000244]; McArthur-Radovsky Fund; Lerner Fund; Harris Fund; Watkins Fund; Gilead Research Scholars Fund; Pulmonary Hypertension Association; Intramural Research Program of the National Human Genome Research Institute; Wellcome Trust [098051] FX We thank our ISCU (mut/mut) patient for her willingness to participate in this study; Allan Bradley for the mmu-miR-210-/- mice; William Kaelin for VHLflox/flox mice; Joff Silberg for GRX2 and GCN4 sensors; Joseph Loscalzo, Jonathan Snow, Brian North, and S.K. Chan for scientific advice; and Stephanie Tribuna for expert administrative assistance. This work was supported by the NIH (K08HL096834 [S.Y.C.], U54-CA151884, R01-DE016516-06, and EB000244 [D.G.A. and R.L.]); the McArthur-Radovsky, Lerner, Harris, and Watkins Funds; Gilead Research Scholars Fund; the Pulmonary Hypertension Association (S.Y.C.); the Intramural Research Program of the National Human Genome Research Institute (B.R.G.); and the Wellcome Trust (098051 [H.M.P.]). NR 62 TC 20 Z9 20 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 EI 1757-4684 J9 EMBO MOL MED JI EMBO Mol. Med. PD JUN PY 2015 VL 7 IS 6 BP 695 EP 713 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CJ7OP UT WOS:000355686400003 PM 25825391 ER PT J AU Nash, TE Mahanty, S Loeb, JA Theodore, WH Friedman, A Sander, JW Singh, G Cavalheiro, E Del Brutto, OH Takayanagui, OM Fleury, A Verastegui, M Preux, PM Montano, S Pretell, EJ White, AC Gonzales, AE Gilman, RH Garcia, HH AF Nash, Theodore E. Mahanty, Siddhartha Loeb, Jeffrey A. Theodore, William H. Friedman, Alon Sander, Josemir W. Singh, Gagandeep Cavalheiro, Esper Del Brutto, Oscar H. Takayanagui, Osvaldo M. Fleury, Agnes Verastegui, Manuela Preux, Pierre-Marie Montano, Silvia Javier Pretell, E. White, A. Clinton, Jr. Gonzales, Armando E. Gilman, Robert H. Garcia, Hector H. TI In response: Multifactorial basis of epilepsy in patients with neurocysticercosis SO EPILEPSIA LA English DT Letter C1 [Nash, Theodore E.; Mahanty, Siddhartha] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Loeb, Jeffrey A.] Univ Illinois, Dept Neurol & Rehabil, Chicago, IL USA. [Theodore, William H.] NINDS, Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Friedman, Alon] Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, IL-84105 Beer Sheva, Israel. [Friedman, Alon] Dalhousie Univ, Dept Med Neurosci, Halifax, NS, Canada. [Sander, Josemir W.] UCL Inst Neurol, Hosp Biomed Res Ctr, Dept Clin & Expt Epilepsy, London, England. [Sander, Josemir W.] London & Epilepsy Soc, Gerrards Cross, Bucks, England. [Sander, Josemir W.] Netherlands Fdn, Epilepsy Inst, Heemstede, Netherlands. [Singh, Gagandeep] Dayan & Med Coll, Dept Neurol, Ludhiana, Punjab, India. [Cavalheiro, Esper] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil. [Del Brutto, Oscar H.] Univ Espiritu Santo, Sch Med, Guayaquil, Ecuador. [Takayanagui, Osvaldo M.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, BR-14049 Ribeirao Preto, Brazil. [Fleury, Agnes] Univ Nacl Autonoma Mexico, Natl Inst Neurol & Neurosurg INNN, Inst Biomed Res, Mexico City 04510, DF, Mexico. [Verastegui, Manuela] Univ Peruana Cayetano Heredia, Fac Sci & Philosophy, Dept Cellular & Mol Sci, Lima, Peru. [Preux, Pierre-Marie] Univ Limoges, CHU Limoges, Inst Neuroepidemiol & Trop Neurol, UMR1094,INSERM, Limoges, France. [Montano, Silvia] US Naval Med Res Unit 6, Callao, Peru. [Javier Pretell, E.] Hosp Alberto Sabogal, Dept Neurol, Callao, Peru. [White, A. Clinton, Jr.] Univ Texas, Div Infect Dis, Dept Internal Med, Galveston, TX USA. [Gonzales, Armando E.] Natl Univ San Marcos, Sch Vet Med, Dept Vet Publ Hlth, Lima, Peru. [Gilman, Robert H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Garcia, Hector H.] Inst Neurol Dis, Cysticercosis Unit, Lima, Peru. [Garcia, Hector H.] Univ Peruana Cayetano Heredia, Ctr Global Hlth Tumbes, Lima, Peru. [Garcia, Hector H.] Univ Peruana Cayetano Heredia, Dept Microbiol, Lima, Peru. RP Nash, TE (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM tnash@niaid.nih.gov RI Sander, Josemir/C-1576-2008; PREUX, Pierre-Marie/B-8393-2014; Takayanagui, Osvaldo/C-8159-2013; OI Sander, Josemir/0000-0001-6041-9661; PREUX, Pierre-Marie/0000-0002-2171-2977; Takayanagui, Osvaldo/0000-0002-8190-0275; White, A Clinton/0000-0002-9668-4632; Mahanty, Siddhartha/0000-0003-1068-0524 FU FIC NIH HHS [D43 TW00114]; Intramural NIH HHS [Z01 AI000846-09]; Wellcome Trust NR 1 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD JUN PY 2015 VL 56 IS 6 BP 975 EP 976 DI 10.1111/epi.12986 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CK1DU UT WOS:000355946900024 PM 26040533 ER PT J AU Chen, ZX Oliver, B AF Chen, Zhen-Xia Oliver, Brian TI X Chromosome and Autosome Dosage Responses in Drosophila melanogaster Heads SO G3-GENES GENOMES GENETICS LA English DT Article DE segmental aneuploidy; sex determination; dosage compensation; sex chromosomes; gene expression; genetics of sex ID RNA-SEQ EXPERIMENTS; LINKED GENES; BIASED EXPRESSION; COPY NUMBER; COMPENSATION; EVOLUTION; ANEUPLOIDY; ALIGNMENT; COMPLEX; MALES AB X chromosome dosage compensation is required for male viability in Drosophila. Dosage compensation relative to autosomes is two-fold, but this is likely to be due to a combination of homeostatic gene-by-gene regulation and chromosome-wide regulation. We have baseline values for gene-by-gene dosage compensation on autosomes, but not for the X chromosome. Given the evolutionary history of sex chromosomes, these baseline values could differ. We used a series of deficiencies on the X and autosomes, along with mutations in the sex-determination gene transformer-2, to carefully measure the sex-independent X-chromosome response to gene dosage in adult heads by RNA sequencing. We observed modest and indistinguishable dosage compensation for both X chromosome and autosome genes, suggesting that the X chromosome is neither inherently more robust nor sensitive to dosage change. C1 [Chen, Zhen-Xia; Oliver, Brian] NIDDK, Sect Dev Gen, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Oliver, B (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM briano@helix.nih.gov FU National Institutes of Health, NIDDK [ZIA-DK015600] FX We thank Harold Smith for sequencing, Hangnoh Lee for reanalysis of published data, Kevin Cook for Df cytology, Helix (http://helix.nih.gov) and Biowulf (http://biowulf.nih.gov) for providing high-performance computational capabilities, FlyBase for files, and our lab for stimulating discussions. We also thank the Bloomington Stock Center and Elissa Lei for fly lines. The Intramural Research Program of the National Institutes of Health, NIDDK (ZIA-DK015600), supported this research. NR 48 TC 6 Z9 6 U1 6 U2 14 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD JUN 1 PY 2015 VL 5 IS 6 BP 1057 EP 1063 DI 10.1534/g3.115.017632 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CK4FC UT WOS:000356176000005 PM 25850426 ER PT J AU Quach, HNB Tao, SJ Vrljicak, P Joshi, A Ruan, H Sukumaran, R Varshney, GK LaFave, MC Burgess, SM Winkler, C Emelyanov, A Parinov, S Sampath, K AF Quach, Helen Ngoc Bao Tao, Shijie Vrljicak, Pavle Joshi, Adita Ruan, Hua Sukumaran, Rashmi Varshney, Gaurav K. LaFave, Matthew C. Burgess, Shawn M. Winkler, Christoph Emelyanov, Alexander Parinov, Sergey Sampath, Karuna CA Ds Screen Team TI A Multifunctional Mutagenesis System for Analysis of Gene Function in Zebrafish SO G3-GENES GENOMES GENETICS LA English DT Article DE functional genomics; insertional mutagenesis; Ac/Ds transposon; gene expression ID DEVELOPMENTALLY-REGULATED GENES; EMBRYONIC STEM-CELLS; BEAUTY TRANSPOSON SYSTEM; MEDAKA ORYZIAS-LATIPES; SLEEPING-BEAUTY; GENOME-WIDE; ENHANCER TRAP; PIGGYBAC TRANSPOSON; VERTEBRATE PROTEOME; XENOPUS-TROPICALIS AB Since the sequencing of the human reference genome, many human disease-related genes have been discovered. However, understanding the functions of all the genes in the genome remains a challenge. The biological activities of these genes are usually investigated in model organisms such as mice and zebrafish. Large-scale mutagenesis screens to generate disruptive mutations are useful for identifying and understanding the activities of genes. Here, we report a multifunctional mutagenesis system in zebrafish using the maize Ds transposon. Integration of the Ds transposable element containing an mCherry reporter for protein trap events and an EGFP reporter for enhancer trap events produced a collection of transgenic lines marking distinct cell and tissue types, and mutagenized genes in the zebrafish genome by trapping and prematurely terminating endogenous protein coding sequences. We obtained 642 zebrafish lines with dynamic reporter gene expression. The characterized fish lines with specific expression patterns will be made available through the European Zebrafish Resource Center (EZRC), and a database of reporter expression is available online (http://fishtrap.warwick.ac.uk/). Our approach complements other efforts using zebrafish to facilitate functional genomic studies in this model of human development and disease. C1 [Quach, Helen Ngoc Bao; Tao, Shijie; Vrljicak, Pavle; Joshi, Adita; Ruan, Hua; Sukumaran, Rashmi; Emelyanov, Alexander; Parinov, Sergey] Natl Univ Singapore, Temasek Life Sci Lab, Singapore 117604, Singapore. [Tao, Shijie; Winkler, Christoph; Sampath, Karuna] Natl Univ Singapore, Dept Biol Sci, Singapore 117604, Singapore. [Vrljicak, Pavle; Sampath, Karuna] Warwick Med Sch, Div Biomed Cell Biol, Coventry CV4 7AJ, W Midlands, England. [Varshney, Gaurav K.; LaFave, Matthew C.; Burgess, Shawn M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Winkler, Christoph] Natl Univ Singapore, Ctr Bioimaging Sci, Singapore 117543, Singapore. RP Sampath, K (reprint author), Univ Warwick, Warwick Med Sch, Div Biomed Cell Biol, Coventry CV4 7AJ, W Midlands, England. EM K.Sampath@warwick.ac.uk RI Winkler, Christoph/G-4822-2012; OI LaFave, Matthew/0000-0001-9165-041X; Varshney, Gaurav K./0000-0002-0429-1904 FU Department of Biological Sciences, National University of Singapore; National Human Genome Research Institute, National Institutes of Health; Warwick Medical School FX We thank the Sampath laboratory and our colleagues in Singapore and Warwick for discussions and suggestions; Hugh Woodland, Lavanya Sivashanmugam, and Jennifer Holden for suggestions to improve the manuscript; Chin Heng Goh and the Temasek Life Sciences Laboratory fish, imaging, and sequencing facilities; and Ian Bagley and the Warwick fish facility for technical support. C.W. is supported by Department of Biological Sciences, National University of Singapore. G.K.V., M.C.L., and S.M.B. were supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. K.S. and P.V. are supported by Warwick Medical School. The authors declare no conflict of interest. NR 78 TC 5 Z9 5 U1 0 U2 15 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD JUN 1 PY 2015 VL 5 IS 6 BP 1283 EP 1299 DI 10.1534/g3.114.015842 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA CK4FC UT WOS:000356176000025 PM 25840430 ER PT J AU Coleman, RL Sill, MW Bell-McGuinn, K Aghajanian, C Gray, HJ Tewari, KS Rubin, SC Rutherford, TJ Chan, JK Chen, A Swisher, EM AF Coleman, Robert L. Sill, Michael W. Bell-McGuinn, Katherine Aghajanian, Carol Gray, Heidi J. Tewari, Krishnansu S. Rubin, Steven C. Rutherford, Thomas J. Chan, John K. Chen, Alice Swisher, Elizabeth M. TI A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - An NRG Oncology/Gynecologic Oncology Group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Veliparib; Ovarian cancer; PARP inhibitor; Toxicity; Phase II trial; BRCA1, BRCA2 mutation ID POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; REFRACTORY SOLID TUMORS; PLATINUM-FREE INTERVAL; HOMOLOGOUS RECOMBINATION; SOMATIC MUTATIONS; OPEN-LABEL; RESISTANCE; SENSITIVITY; COMBINATION; OLAPARIB AB Background. Veliparib is a potent small molecule inhibitor of PARP-1/2, which is cytotoxic in tumor cells with deficiencies in BRCA1 or BRCA2. We studied the clinical activity and toxicity of veliparib in ovarian cancer patients carrying a germline BRCA1 or BRCA2 mutation (gBRCA). Methods. Eligibility included three or fewer prior chemotherapy regimens, measurable disease and no prior use of a PARP inhibitor. Veliparib was administered at 400 mg orally BID with one cycle being 28 days. The two-stage Simon design was capable of detecting a 25% response probability with 90% power while controlling alpha = 10% (at a 10% assumed null response probability). Results. The median age of the 50 eligible patients was 57 years (range 37-94) and 14, 18, and 18 patients had I, 2, and 3 prior therapies respectively. Thirty patients (60%) were platinum-resistant. The median number of cycles administered was 6 (1-27). There was one grade 4 thrombocytopenia. Grade 3 adverse events were: fatigue (n = 3), nausea (2), leukopenia (1), neutropenia (1), dehydration (1), and ALT (1). Grade 2 events >10% were: nausea (46%), fatigue (26%), vomiting (18%), and anemia (14%). The proportion responding was 26% (90% Cl: 16%-38%, CR: 2, PR: 11); for platinum-resistant and platinum-sensitive patients the proportion responding was 20% and 35%, respectively. The most common reason for treatment discontinuation was progression (62%). Twenty-nine patients are alive; two with SD remain on veliparib. The median PFS is 8.18 months. Conclusions. The single agent efficacy and tolerability of veliparib for BRCA mutation-associated recurrent ovarian cancer warrants further investigation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Sill, Michael W.] Roswell Pk Canc Inst, NRG Stat & Data Ctr, Buffalo, NY 14263 USA. [Bell-McGuinn, Katherine; Aghajanian, Carol] Mem Sloan Kettering Canc Ctr, Med Oncol, New York, NY 10021 USA. [Gray, Heidi J.] Univ Washington, Dept OB GYN, Seattle, WA 98195 USA. [Tewari, Krishnansu S.] Univ Calif Irvine, Med Ctr, Irvine Chao Family Comprehens Canc Ctr, Dept Obstet & Gynecol, Orange, CA 92868 USA. [Rubin, Steven C.] Fox Chase Canc Ctr, Surg Oncol, Philadelphia, PA 19111 USA. [Rutherford, Thomas J.] Yale Univ, Sch Med, Div GYN Oncol, New Haven, CT 06520 USA. [Chan, John K.] Palo Alto Med Fdn, San Francisco, CA 94118 USA. [Chen, Alice] NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD 20892 USA. [Swisher, Elizabeth M.] Univ Washington, Seattle, WA 98109 USA. [Swisher, Elizabeth M.] Fred Hutchinson Canc Res Ctr, Puget Sound Oncol Consortium, Seattle, WA 98109 USA. RP Coleman, RL (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, 1155 Herman Pressler Dr,CPB 6-3590, Houston, TX 77030 USA. EM rcoleman@mdanderson.org FU National Cancer Institute [CA 27469, CA 37517]; NIH [P50 CA098258]; Ann Rife Cox Chair in Gynecology FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical and Data Center (CA 37517). This was also supported, in part, by NIH grant P50 CA098258.; Dr. Coleman is supported in part by the Ann Rife Cox Chair in Gynecology. We also acknowledge Abbvie (North Chicago, Ill) for providing the investigational drug. NR 41 TC 40 Z9 43 U1 5 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2015 VL 137 IS 3 BP 386 EP 391 DI 10.1016/j.ygyno.2015.03.042 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CJ8UM UT WOS:000355779000005 PM 25818403 ER PT J AU Temkin, SM Fleming, SA Amrane, S Schluterman, N Terplan, M AF Temkin, Sarah M. Fleming, Saroj A. Amrane, Selma Schluterman, Nicholas Terplan, Mishka TI Geographic disparities amongst patients with gynecologic malignancies at an urban NCI-designated cancer center SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Gynecologic cancer; Treatment adherence; Disparities ID STAGE BREAST-CANCER; OVARIAN-CANCER; TREATMENT GUIDELINES; RADIATION-THERAPY; TRAVEL DISTANCE; UTERINE-CANCER; UNITED-STATES; LUNG-CANCER; IMPACT; CARE AB Objective. Women with gynecologic malignancies require specialized care. We hypothesize that a geographic disparity exists amongst patients with gynecologic malignancies and that longer distance and time traveled negatively impact completion of adjuvant therapy. Methods. Patients with incident gynecologic malignancies at a single, urban NCI-designated cancer center were identified. Distances from the patient's home to the treating facility were calculated in miles and minutes. Demographic variables were evaluated for their impact on treatment outcomes using Chi-squared, ANOVA and Kruskal Wallis analyses. Results. One hundred and fifty consecutive patients were identified. The median distance traveled to the hospital was 16.9 miles with a median travel time of 28 min. The distance and time traveled were significantly different between insurance groups, with the uninsured traveling the furthest for care by distance (p = 0.04) and time (p = 0.03). Race, tumor site, medical comorbidities and median income at zip code were not associated with travel distance or time to the hospital. The majority of patients (87%) completed recommended initial treatment. Treatment completion was related to distance traveled with those patients living at the distance extremes (<10 miles or >50 miles) least likely to complete care (p < 0.01). The presence of medical comorbidities (p < 0.01) but not insurance status was correlated to treatment completion. Conclusions. Geographic disparities exist in women with gynecologic malignancies receiving treatment at an NCI-designated cancer center. Approaches to decreasing these disparities may include improved support for cancer patients needing assistance with travel and additional social work and psychosocial support to patients with medical co-morbidities. (C) 2015 Elsevier Inc. All rights reserved. C1 [Temkin, Sarah M.; Fleming, Saroj A.; Amrane, Selma] Univ Maryland, Sch Med, Dept Obstet Gynecol & Reprod Sci, Baltimore, MD 21201 USA. [Schluterman, Nicholas; Terplan, Mishka] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. RP Temkin, SM (reprint author), NCI, Canc Prevent Div, NIH, Hlth & Human Serv, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM temkinsm@mail.nih.gov NR 26 TC 7 Z9 7 U1 3 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2015 VL 137 IS 3 BP 497 EP 502 DI 10.1016/j.ygyno.2015.03.010 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CJ8UM UT WOS:000355779000023 PM 25795262 ER PT J AU Silverman, LR Greenberg, P Raza, A Olnes, MJ Holland, JF Reddy, P Maniar, M Wilhelm, F AF Silverman, Lewis R. Greenberg, Peter Raza, Azra Olnes, Matthew J. Holland, James F. Reddy, Premkumar Maniar, Manoj Wilhelm, Francois TI Clinical activity and safety of the dual pathway inhibitor rigosertib for higher risk myelodysplastic syndromes following DNA methyltransferase inhibitor therapy SO HEMATOLOGICAL ONCOLOGY LA English DT Article DE myelodysplastic syndromes; polo-like kinase; phosphatidylinositol 3-kinase; ON 01910; Na; rigosertib; DNA methyl transferase inhibitors ID ACUTE MYELOID-LEUKEMIA; PROGNOSTIC SCORING SYSTEM; SYNDROMES MDS; CYCLIN D1; AZACITIDINE; DIAGNOSIS; SURVIVAL; 01910.NA; DATABASE; FAILURE AB Rigosertib (ON 01910.Na) is an inhibitor of the phosphoinositide 3-kinase and polo-like kinase pathways that induces mitotic arrest and apoptosis in neoplastic cells, while sparing normal cells. Our purpose is to summarize the clinical activity and safety of intravenous (IV) rigosertib delivered by an external ambulatory infusion pump in patients with refractory anemia with excess blasts-1, -2, or, -t myelodysplastic syndromes (MDS) following prior treatment with DNA methyltransferase (DNMT) inhibitors. A total of 39 patients with MDS who fulfilled these criteria were enrolled in four phase 1-2 clinical trials of IV rigosertib. Thirty five (88%) had higher risk disease according to the Revised International Prognostic Scoring System. Median overall survival for this group of 39 patients was 35weeks. Of 30 evaluable patients with follow-up bone marrow biopsies, 12 (40%) achieved complete (n=5) or partial (n=7) bone marrow blast responses. In addition, 15 patients achieved stabilization of bone marrow blasts. One patient with a complete bone marrow response also achieved a complete cytogenetic response. A second patient with stable bone marrow blasts achieved a partial cytogenetic response. Two of the responding patients and three patients with stable disease had hematological improvements. Rigosertib-induced bone marrow blast decreases and stability appeared to be predictive of prolonged survival. IV rigosertib had a favorable safety profile without significant myelosuppression. Most common drug-related toxicities included fatigue, diarrhea, nausea, dysuria, and hematuria. In summary, IV rigosertib is well tolerated and has clinical activity in patients with higher risk MDS following DNMT inhibitor treatment. A multinational pivotal phase 3 randomized clinical trial of rigosertib versus best supportive care for patients with MDS with excess blasts following prior treatment with DNMT inhibitors (ONTIME: ON 01910.Na Trial In Myelodysplastic SyndromE) has recently completed enrollment. (c) 2014 The Authors. Hematological Oncology published by John Wiley & Sons, Ltd. C1 [Silverman, Lewis R.; Holland, James F.; Reddy, Premkumar] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Greenberg, Peter] Stanford Univ, Ctr Canc, Dept Med Hematol, Stanford, CA 94305 USA. [Raza, Azra] Columbia Univ, Med Ctr, New York, NY USA. [Olnes, Matthew J.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Maniar, Manoj; Wilhelm, Francois] Onconova Therapeut Inc, Pennington, NJ 08534 USA. RP Wilhelm, F (reprint author), Onconova Therapeut Inc, 73 Route 31 North,Suite B, Pennington, NJ 08534 USA. EM FWilhelm@onconova.us FU Intramural Program of the Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health; Onconova Therapeutics, Inc. FX Onconova Therapeutics, Inc., the manufacturer of rigosertib, funded the four clinical trials discussed in this report. In addition, this work was supported in part by the Intramural Program of the Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health. The clinical investigators and the study sponsor, Onconova Therapeutics, Inc., played a key role in study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the report for publication. Dr. J. F Holland has served as consultant to Onconova Therapeutics, Inc. Dr. P. Reddy is the scientific founder of Onconova Therapeutics, Inc. Drs. M. Maniar and F. Wilhelm are employees of Onconova Therapeutics, Inc. Clinical investigators disclosed their potential conflicts to study participants. NR 28 TC 13 Z9 13 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0278-0232 EI 1099-1069 J9 HEMATOL ONCOL JI Hematol. Oncol. PD JUN PY 2015 VL 33 IS 2 BP 57 EP 66 DI 10.1002/hon.2137 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA CK6JZ UT WOS:000356335700001 PM 24777753 ER PT J AU Ng, BG Wolfe, LA Ichikawa, M Markello, T He, M Tifft, CJ Gahl, WA Freeze, HH AF Ng, Bobby G. Wolfe, Lynne A. Ichikawa, Mie Markello, Thomas He, Miao Tifft, Cynthia J. Gahl, William A. Freeze, Hudson H. TI Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decrease glycosylation precursors SO HUMAN MOLECULAR GENETICS LA English DT Article ID COLI ASPARTATE TRANSCARBAMOYLASE; POSTAXIAL ACROFACIAL DYSOSTOSIS; MULTIFUNCTIONAL PROTEIN CAD; HEREDITARY OROTIC ACIDURIA; HUMAN UMP SYNTHASE; NUCLEOTIDE SUGARS; MOLECULAR-CLONING; DOMAIN; SEQUENCE; GENE AB In mitochondria, carbamoyl-phosphate synthetase 1 activity produces carbamoyl phosphate for urea synthesis, and deficiency results in hyperammonemia. Cytoplasmic carbamoyl-phosphate synthetase 2, however, is part of a tri-functional enzyme encoded by CAD; no human disease has been attributed to this gene. The tri-functional enzyme contains carbamoyl-phosphate synthetase 2 (CPS2), aspartate transcarbamylase (ATCase) and dihydroorotase (DHOase) activities, which comprise the first three of six reactions required for de novo pyrimidine biosynthesis. Here we characterize an individual who is compound heterozygous for mutations in different domains of CAD. One mutation, c.1843-1G > A, results in an in-frame deletion of exon 13. The other, c.6071G > A, causes a missense mutation (p.Arg2024Gln) in a highly conserved residue that is essential for carbamoyl-phosphate binding. Metabolic flux studies showed impaired aspartate incorporation into RNA and DNA through the de novo synthesis pathway. In addition, CTP, UTP and nearly all UDP-activated sugars that serve as donors for glycosylation were decreased. Uridine supplementation rescued these abnormalities, suggesting a potential therapy for this new glycosylation disorder. C1 [Ng, Bobby G.; Ichikawa, Mie; Freeze, Hudson H.] Sanford Burnham Med Res Inst, Human Genet Program, La Jolla, CA 92037 USA. [Wolfe, Lynne A.; Markello, Thomas; Tifft, Cynthia J.; Gahl, William A.] NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bethesda, MD 20892 USA. [Tifft, Cynthia J.; Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA. [He, Miao] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19103 USA. RP Freeze, HH (reprint author), Sanford Burnham Med Res Inst, Human Genet Program, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM hudson@sanfordburnham.org OI Freeze, Hudson/0000-0001-6316-0501 FU Rocket Fund; National Institutes of Health (NIH) [R01DK099551, R01DK55615]; Common Fund of the Office of the Director, NIH; Intramural Research Program of the National Human Genome Research Institute FX Supported in part by The Rocket Fund, National Institutes of Health (NIH) grants (R01DK099551 and R01DK55615 to H.H.F), the Common Fund of the Office of the Director, NIH and the Intramural Research Program of the National Human Genome Research Institute. NR 31 TC 6 Z9 7 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2015 VL 24 IS 11 BP 3050 EP 3057 DI 10.1093/hmg/ddv057 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CJ7KN UT WOS:000355674000005 PM 25678555 ER PT J AU Sharma, P Rayavara, K Ito, D Basore, K Desai, SA AF Sharma, Paresh Rayavara, Kempaiah Ito, Daisuke Basore, Katherine Desai, Sanjay A. TI A CLAG3 Mutation in an Amphipathic Transmembrane Domain Alters Malaria Parasite Nutrient Channels and Confers Leupeptin Resistance SO INFECTION AND IMMUNITY LA English DT Article ID SURFACE ANION CHANNEL; FALCIPARUM-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; RHOPTRY PROTEIN COMPLEX; PLASMODIUM-FALCIPARUM; IN-VITRO; GENES; MEMBRANE; COMPONENT; INVASION AB Erythrocytes infected with malaria parasites have increased permeability to ions and nutrients, as mediated by the plasmodial surface anion channel (PSAC) and recently linked to parasite clag3 genes. Although the encoded protein is integral to the host membrane, its precise contribution to solute transport remains unclear because it lacks conventional transmembrane domains and does not have homology to ion channel proteins in other organisms. Here, we identified a probable CLAG3 transmembrane domain adjacent to a variant extracellular motif. Helical-wheel analysis revealed strict segregation of polar and hydrophobic residues to opposite faces of a predicted alpha-helical transmembrane domain, suggesting that the domain lines a water-filled pore. A single CLAG3 mutation (A1210T) in a leupeptin-resistant PSAC mutant falls within this transmembrane domain and may affect pore structure. Allelic-exchange transfection and site-directed mutagenesis revealed that this mutation alters solute selectivity in the channel. The A1210T mutation also reduces the blocking affinity of PSAC inhibitors that bind on opposite channel faces, consistent with global changes in channel structure. Transfected parasites carrying this mutation survived a leupeptin challenge significantly better than a transfection control did. Thus, the A1210T mutation contributes directly to both altered PSAC activity and leupeptin resistance. These findings reveal the molecular basis of a novel antimalarial drug resistance mechanism, provide a framework for determining the channel's composition and structure, and should guide the development of therapies targeting the PSAC. C1 [Sharma, Paresh; Rayavara, Kempaiah; Ito, Daisuke; Basore, Katherine; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20817 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20817 USA. EM sdesai@niaid.nih.gov OI Basore, Katherine/0000-0001-5974-0968 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 49 TC 5 Z9 5 U1 0 U2 2 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 2015 VL 83 IS 6 BP 2566 EP 2574 DI 10.1128/IAI.02966-14 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CK5DS UT WOS:000356243000033 PM 25870226 ER PT J AU Adler-Wailes, DC Alberobello, AT Ma, X Hugendubler, L Stern, EA Mou, Z Han, JC Kim, PW Sumner, AE Yanovski, JA Mueller, E AF Adler-Wailes, D. C. Alberobello, A. T. Ma, X. Hugendubler, L. Stern, E. A. Mou, Z. Han, J. C. Kim, P. W. Sumner, A. E. Yanovski, J. A. Mueller, E. TI Analysis of variants and mutations in the human winged helix FOXA3 gene and associations with metabolic traits SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID TRANSCRIPTION FACTORS; LIVER DEVELOPMENT; PHOSPHORYLATION; OBESITY; GROWTH; FAMILY AB BACKGROUND/OBJECTIVES: The forkhead factor Foxa3 is involved in the early transcriptional events controlling adipocyte differentiation and plays a critical function in fat depot expansion in response to high-fat diet regimens and during aging in mice. No studies to date have assessed the potential associations of genetic variants in FOXA3 with human metabolic outcomes. SUBJECTS/METHODS: In this study, we sequenced FOXA3 in 392 children, adolescents and young adults selected from several cohorts of subjects recruited at the National Institute of Child Health and Human Development of the National Institutes of Health based on the availability of dual-energy X-ray absorptiometry data, magnetic resonance imaging scans and DNA samples. We assessed the association between variants present in these subjects and metabolic traits and performed in vitro functional analysis of two novel FOXA3 missense mutations identified. RESULTS: Our analysis identified 14 novel variants and showed that the common single-nucleotide polymorphism (SNP) rs28666870 is significantly associated with greater body mass index, lean body mass and appendicular lean mass (P values 0.009, 0.010 and 0.013 respectively). In vitro functional studies showed increased adipogenic function for the FOXA3 missense mutations c.185C>T (p.Ser62Leu) and c.731C>T (p.Ala244Val) compared with FOXA3-WT. CONCLUSIONS: Our study identified novel FOXA3 variants and mutations, assessed the adipogenic capacity of two novel missense alterations in vitro and demonstrated for the first time the associations between FOXA3 SNP rs28666870 with metabolic phenotypes in humans. C1 [Adler-Wailes, D. C.; Alberobello, A. T.; Ma, X.; Hugendubler, L.; Mueller, E.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Stern, E. A.; Mou, Z.; Han, J. C.; Yanovski, J. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Growth & Obes, Program Dev Endocrinol & Genet, Bethesda, MD USA. [Kim, P. W.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Sumner, A. E.] NIDDK, Diabet Endocrinol & Obes Branch, Sect Ethn & Hlth, NIH, Bethesda, MD 20892 USA. RP Mueller, E (reprint author), NIDDK, NIH, Bldg 10,Room 8D12b,9000 Rockville Pike, Bethesda, MD 20892 USA. EM elisabettam@mail.nih.gov FU NIDDK; NICHD; NIMHD; NIAMS of the National Institutes of Health FX We thank Pasha Sarraf for thoughtful discussions throughout the project and Chen Du and Lingyan Xu for reading the manuscript. We are grateful to the families who participated in the study. JAY is a Commissioned Officer in the United States Public Health Service. This work was supported by the Intramural Research Programs of NIDDK, NICHD, NIMHD and NIAMS of the National Institutes of Health. NR 17 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD JUN PY 2015 VL 39 IS 6 BP 888 EP 892 DI 10.1038/ijo.2015.17 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CK2KO UT WOS:000356039500003 PM 25672906 ER PT J AU Aderibigbe, OM Priel, DL Lee, CCR Ombrello, MJ Prajapati, VH Liang, MG Lyons, JJ Kuhns, DB Cowen, EW Milner, JD AF Aderibigbe, Oyinade M. Priel, Debra Long Lee, Chyi-Chia Richard Ombrello, Michael J. Prajapati, Vimal H. Liang, Marilyn G. Lyons, Jonathan J. Kuhns, Douglas B. Cowen, Edward W. Milner, Joshua D. TI Distinct Cutaneous Manifestations and Cold-Induced Leukocyte Activation Associated With PLCG2 Mutations SO JAMA DERMATOLOGY LA English DT Article ID DEFECTIVE NEUTROPHIL MIGRATION; NECROBIOSIS LIPOIDICA; GRANULOMATOUS-DISEASE; IMMUNODEFICIENCY; SARCOIDOSIS; ANNULARE; INFLUX AB IMPORTANCE PLCG2-associated antibody deficiency and immune dysregulation (PLAID) is a newly characterized immunodeficiency syndrome associated with distinct cutaneous features. Awareness of the cutaneous skin findings associated with PLAID may facilitate diagnosis and improve patient care. OBJECTIVES To characterize the cutaneous manifestations of PLAID and identify potential cellular mechanisms of the disease. DESIGN, SETTING, AND PARTICIPANTS In this retrospective analysis of patients with PLAID and PLAID-like disease evaluated at the National Institutes of Health from January 1, 2005, through December 31, 2014, patients with deletions in PLCG2 leading to PLAID and patients with PLAID-like disease for whom a PLAID mutation was not identified were studied. MAIN OUTCOMES AND MEASURES Characterization of cutaneous manifestations of PLAID and PLAID-like disease and analysis of PLAID immune cell activation. RESULTS Among 36 patients with PLAID and PLAID-like phenotypes, all of whom had evaporative cold urticaria, 8 patients had a history of unique neonatal-onset ulcerative and cutaneous lesions in cold-sensitive regions of the body. Granulomatous skin lesions sparing warm regions (eg, flexural surfaces and skinfolds) were identified in 4 patients. Neutrophils and monocytes from patients with PLAID exhibited enhanced baseline activation in vitro, which was potentiated by ambient temperature exposure. CONCLUSIONS AND RELEVANCE Collectively, these findings suggest that early identification of neonatal lesions may help in the diagnosis of PLAID and that leukocyte hyperactivation may underlie cutaneous lesions in patients with PLAID. Further characterization of mechanisms underlying leukocyte hyperactivation may contribute to the fundamental understanding of granuloma formation. C1 [Aderibigbe, Oyinade M.; Priel, Debra Long; Lyons, Jonathan J.; Kuhns, Douglas B.; Milner, Joshua D.] NIAID, Bethesda, MD 20892 USA. [Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Ombrello, Michael J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Prajapati, Vimal H.; Liang, Marilyn G.] Harvard Univ, Sch Med, Boston Childrens Hosp, Pediat Dermatol, Boston, MA USA. [Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Milner, JD (reprint author), NIAID, 10 Ctr Dr,Bldg 10-CRC,Room 5-3950, Bethesda, MD 20892 USA. EM jdmilner@niaid.nih.gov OI Lyons, Jonathan/0000-0002-2346-8189 FU Intramural Research Program of the National Institutes of Health; National Institute of Allergy and Infectious Diseases; National Institutes of Health Medical Research Scholars Program; National Institutes of Health FX This study was supported in part by the Intramural Research Program of the National Institutes of Health, the National Institute of Allergy and Infectious Diseases, and the National Institutes of Health Medical Research Scholars Program, a public-private partnership supported jointly by the National Institutes of Health and generous contributions to the Foundation for the National Institutes of Health from Pfizer Inc, The Doris Duke Charitable Foundation, The Alexandria Real Estate Equities Inc, Mr. and Mrs. Joel S. Marcus, and the Howard Hughes Medical Institute, as well as other private donors. NR 17 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD JUN PY 2015 VL 151 IS 6 BP 627 EP 634 DI 10.1001/jamadermatol.2014.5641 PG 8 WC Dermatology SC Dermatology GA CK4FN UT WOS:000356177700010 PM 25760457 ER PT J AU Ding, J Sigurdsson, S Garcia, M Phillips, CL Eiriksdottir, G Gudnason, V van Buchem, MA Launer, LJ AF Ding, Jie Sigurdsson, Sigurdur Garcia, Melissa Phillips, Caroline L. Eiriksdottir, Gudny Gudnason, Vilmundur van Buchem, Mark A. Launer, Lenore J. TI Risk Factors Associated With Incident Cerebral Microbleeds According to Location in Older People The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study SO JAMA NEUROLOGY LA English DT Article ID SERUM TOTAL CHOLESTEROL; INTRACEREBRAL HEMORRHAGE; STROKE; PREVALENCE; LIPOPROTEINS; POPULATION; METAANALYSIS; ROTTERDAM; REYKJAVIK; DISEASE AB IMPORTANCE The spatial distribution of cerebral microbleeds (CMBs), which are asymptomatic precursors of intracerebral hemorrhage, reflects specific underlying microvascular abnormalities of cerebral amyloid angiopathy (lobar structures) and hypertensive vasculopathy (deep brain structures). Relatively little is known about the occurrence of and modifiable risk factors for developing CMBs, especially in a lobar location, in the general population of older people. OBJECTIVE To investigate whether lifestyle and lipid factors predict new CMBs in relation to their anatomic location. DESIGN, SETTING, AND PARTICIPANTS We enrolled 2635 individuals aged 66 to 93 years from the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study in a brain imaging study. Participants underwent a baseline magnetic resonance imaging (MRI) examination of the brain from September 1, 2002, through February 28, 2006, and returned for a second MRI examination from April 1, 2007, through September 30, 2011. EXPOSURES Lifestyle and lipid factors assessed at baseline included smoking, alcohol consumption, body mass index, and serum levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides. MAIN OUTCOMES AND MEASURES Incident CMBs detected on MRIs, which were further categorized as exclusively lobar or as deep. RESULTS During a mean follow-up of 5.2 years, 486 people (18.4%) developed new CMBs, of whom 308 had lobar CMBs only and 178 had deep CMBs. In the multivariate logarithm-binomial regression model adjusted for baseline cardiovascular risk factors, including blood pressure, antihypertensive use, prevalent CMBs, and markers of cerebral ischemic small-vessel disease, heavy alcohol consumption (vs light to moderate consumption; relative risk [RR], 2.94 [95% CI, 1.23-7.01]) was associated with incident CMBs in a deep location. Baseline underweight (vs normal weight; RR, 2.41 [95% CI, 1.21-4.80]), current smoking (RR, 1.47 [95% CI, 1.11-1.94]), an elevated serum level of high-density lipoprotein cholesterol (RR per 1-SD increase, 1.13 [95% CI, 1.02-1.25]), and a decreased triglyceride level (RR per 1-SD decrease in natural logarithm-transformed triglyceride level, 1.17 [95% CI, 1.03-1.33]) were significantly associated with an increased risk for lobar CMBs exclusively but not for deep CMBs. CONCLUSIONS AND RELEVANCE Lifestyle and lipid risk profiles for CMBs were similar to those for symptomatic intracerebral hemorrhage and differed for lobar and deep CMBs. Modification of these risk factors could have the potential to prevent new-onset CMBs, particularly those occurring in a lobar location. C1 [Ding, Jie; Garcia, Melissa; Phillips, Caroline L.; Launer, Lenore J.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20814 USA. [Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. RP Launer, LJ (reprint author), NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, NIH, 7201 Wisconsin Ave,Ste 3C-309, Bethesda, MD 20814 USA. EM LaunerL@nia.nih.gov RI Gudnason, Vilmundur/K-6885-2015; Ding, Jie/K-9943-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084; FU National Institutes of Health [N01-AG-12100]; Intramural Research Program of the National Institute on Aging; Icelandic Heart Association; Icelandic Parliament FX The AGES-Reykjavik Study was funded by contract N01-AG-12100 from the National Institutes of Health; by the Intramural Research Program of the National Institute on Aging; and by the Icelandic Heart Association and the Icelandic Parliament. NR 39 TC 14 Z9 14 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JUN PY 2015 VL 72 IS 6 BP 682 EP 688 DI 10.1001/jamaneurol.2015.0174 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CK1BC UT WOS:000355939400013 PM 25867544 ER PT J AU Zukosky, K Meilleur, K Traynor, BJ Dastgir, J Medne, L Devoto, M Collins, J Rooney, J Zou, YQ Yang, ML Gibbs, JR Meier, M Stetefeld, J Finkel, RS Schessl, J Elman, L Felice, K Ferguson, TA Ceyhan-Birsoy, O Beggs, AH Tennekoon, G Johnson, JO Bonnemann, CG AF Zukosky, Kristen Meilleur, Katherine Traynor, Bryan J. Dastgir, Jahannaz Medne, Livija Devoto, Marcella Collins, James Rooney, Jachinta Zou, Yaqun Yang, Michele L. Gibbs, J. Raphael Meier, Markus Stetefeld, Joerg Finkel, Richard S. Schessl, Joachim Elman, Lauren Felice, Kevin Ferguson, Toby A. Ceyhan-Birsoy, Ozge Beggs, Alan H. Tennekoon, Gihan Johnson, Janel O. Boennemann, Carsten G. TI Association of a Novel ACTA1 Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family SO JAMA NEUROLOGY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; ALPHA-ACTIN GENE; TRABECULAR MUSCLE-FIBERS; DNA-SEQUENCING DATA; NEMALINE MYOPATHY; CONGENITAL MYOPATHIES; PHENOTYPE; ACTINOPATHIES; ZEBRAFISH; DYSTROPHY AB IMPORTANCE New genomic strategies can now be applied to identify a diagnosis in patients and families with previously undiagnosed rare genetic conditions. The large family evaluated in the present study was described in 1966 and now expands the phenotype of a known neuromuscular gene. OBJECTIVE To determine the genetic cause of a slowly progressive, autosomal dominant, scapuloperoneal neuromuscular disorder by using linkage and exome sequencing. DESIGN, SETTING, AND PARTICIPANTS Fourteen affected individuals in a 6-generation family with a progressive scapuloperoneal disorder were evaluated. Participants were examined at pediatric, neuromuscular, and research clinics from March 1, 2005, to May 31, 2014. Exome and linkage were performed in genetics laboratories of research institutions. MAIN OUTCOMES AND MEASURES Examination and evaluation by magnetic resonance imaging, ultrasonography, electrodiagnostic studies, and muscle biopsies (n = 3). Genetic analysis included linkage analysis (n = 17) with exome sequencing (n = 7). RESULTS Clinical findings included progressive muscle weakness in an initially scapuloperoneal and distal distribution, including wrist extensor weakness, finger and foot drop, scapular winging, mild facial weakness, Achilles tendon contractures, and diminished or absent deep tendon reflexes. Both age at onset and progression of the disease showed clinical variability within the family. Muscle biopsy specimens demonstrated type I fiber atrophy and trabeculated fibers without nemaline rods. Analysis of exome sequences within the linkage region (4.8 megabases) revealed missense mutation c.591C>A p.Glu197Asp in a highly conserved residue in exon 4 of ACTA1. The mutation cosegregated with disease in all tested individuals and was not present in unaffected individuals. CONCLUSIONS AND RELEVANCE This family defines a new scapuloperoneal phenotype associated with an ACTA1 mutation. A highly conserved protein, ACTA1 is implicated in multiple muscle diseases, including nemaline myopathy, actin aggregate myopathy, fiber-type disproportion, and rod-core myopathy. To our knowledge, mutations in Glu197 have not been reported previously. This residue is highly conserved and located in an exposed position in the protein; the mutation affects the intermolecular and intramolecular electrostatic interactions as shown by structural modeling. The mutation in this residue does not appear to lead to rod formation or actin accumulation in vitro or in vivo, suggesting a different molecular mechanism from that of other ACTA1 diseases. C1 [Zukosky, Kristen; Rooney, Jachinta; Zou, Yaqun; Boennemann, Carsten G.] NINDS, NIH, Bethesda, MD 20814 USA. [Meilleur, Katherine] NINR, NIH, Bethesda, MD 20892 USA. [Traynor, Bryan J.; Johnson, Janel O.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, Porter Neurosci Res Ctr,NIH, Bethesda, MD 20892 USA. [Dastgir, Jahannaz] Columbia Univ, Med Ctr, Div Child Neurol, New York, NY USA. [Medne, Livija; Tennekoon, Gihan] Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA. [Devoto, Marcella] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Devoto, Marcella] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Devoto, Marcella] Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy. [Devoto, Marcella] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA. [Collins, James] Cincinnati Childrens Hosp Med Ctr, Dept Neurol, Cincinnati, OH 45229 USA. [Rooney, Jachinta] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. [Yang, Michele L.] Childrens Hosp Colorado, Dept Pediat & Neurol, Aurora, CO USA. [Gibbs, J. Raphael] NIA, Computat Biol Core, Neurogenet Lab, Porter Neurosci Res Ctr,NIH, Bethesda, MD 20892 USA. [Meier, Markus; Stetefeld, Joerg] Univ Manitoba, Dept Chem Microbiol Biochem & Med Genet, Winnipeg, MB, Canada. [Finkel, Richard S.] Nemours Childrens Hosp, Dept Pediat, Orlando, FL USA. [Schessl, Joachim] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80539 Munich, Germany. [Elman, Lauren] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Felice, Kevin] Hosp Special Care, Dept Neuromuscular Med, New Britain, CT USA. [Ferguson, Toby A.] Temple Univ, Dept Neurol, Shriners Pediat Res Ctr, Philadelphia, PA 19122 USA. [Ceyhan-Birsoy, Ozge; Beggs, Alan H.] Harvard Univ, Sch Med, Manton Ctr Orphan Dis Res, Div Genet & Gen,Boston Childrens Hosp, Boston, MA USA. RP Bonnemann, CG (reprint author), NINDS, NIH, 35 Convent Dr,MSC 3705,Room 2A116, Bethesda, MD 20814 USA. EM carsten.bonnemann@nih.gov OI Stetefeld, Joerg/0000-0003-1478-3248 FU Division of Intramural Research of the National Institutes of Neurological Disorders and Stroke; National Institute on Aging; National Institutes of Health [R01 HD075802, R01 AR044345]; Muscular Dystrophy Association (United States) [MDA201302]; AUism Charitable Foundation; Foundation Building Strength; Canadian Institute of Health Research/Manitoba Health Research Council Regional Partnership Program Grant [RPA-109759]; Dubai-Harvard Foundation for Medical Research postdoctoral fellowship; Schlumberger Foundation Faculty for the Future grant FX This study was funded in part by the Division of Intramural Research of the National Institutes of Neurological Disorders and Stroke and the National Institute on Aging. This work was supported in part by National Institutes of Health grants R01 HD075802 and R01 AR044345, the Muscular Dystrophy Association (United States) MDA201302, the AUism Charitable Foundation, and A Foundation Building Strength (Dr Beggs). Dr Stetefeld is a Canada Research Chair in Structural Biology, and this research was funded by the Canadian Institute of Health Research/Manitoba Health Research Council Regional Partnership Program Grant RPA-109759. Dr Ceyhan-Birsoy was supported by a Dubai-Harvard Foundation for Medical Research postdoctoral fellowship and a Schlumberger Foundation Faculty for the Future grant. NR 32 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JUN PY 2015 VL 72 IS 6 BP 689 EP 698 DI 10.1001/jamaneurol.2015.37 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CK1BC UT WOS:000355939400014 PM 25938801 ER PT J AU Teach, SJ Gergen, PJ Szefler, SJ Mitchell, HE Calatroni, A Wildfire, J Bloomberg, GR Kercsmar, CM Liu, AH Makhija, MM Matsui, E Morgan, W O'Connor, G Busse, WW AF Teach, Stephen J. Gergen, Peter J. Szefler, Stanley J. Mitchell, Herman E. Calatroni, Agustin Wildfire, Jeremy Bloomberg, Gordon R. Kercsmar, Carolyn M. Liu, Andrew H. Makhija, Melanie M. Matsui, Elizabeth Morgan, Wayne O'Connor, George Busse, William W. TI Seasonal risk factors for asthma exacerbations among inner-city children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; seasons; biomarkers; asthma exacerbations; IgE; exhaled nitric oxide; allergy; eosinophils; pulmonary function ID EXHALED NITRIC-OXIDE; CHILDHOOD ASTHMA; TRIAL; ADOLESCENTS; INFECTIONS; ADULTS; EPIDEMIOLOGY; OMALIZUMAB; EXPOSURE; ALLERGEN AB Background: Asthma exacerbations remain common, even in children and adolescents, despite optimal medical management. Identification of host risk factors for exacerbations is incomplete, particularly for seasonal episodes. Objective: We sought to define host risk factors for asthma exacerbations unique to their season of occurrence. Methods: This is a retrospective analysis of patients aged 6 to 20 years who comprised the control groups of the Asthma Control Evaluation study and the Inner City Anti-IgE Therapy for Asthma study. Univariate and multivariate models were constructed to determine whether patients' demographic and historical factors, allergic sensitization, fraction of exhaled nitric oxide values, spirometric measurements, asthma control, and treatment requirements were associated with seasonal exacerbations. Results: The analysis included 400 patients (54.5% male; 59.0% African American; median age, 13 years). Exacerbations occurred in 37.5% of participants over the periods of observation and were most common in the fall (28.8% of participants). In univariate analysis impaired pulmonary function was significantly associated with greater odds of exacerbations for all seasons, as was an exacerbation in the previous season for all seasons except spring. In multivariate analysis exacerbation in the previous season was the strongest predictor in fall and winter, whereas a higher requirement for inhaled corticosteroids was the strongest predictor in spring and summer. The multivariate models had the best predictive power for fall exacerbations (30.5% variance attributed). Conclusions: Among a large cohort of inner-city children with asthma, patients' risk factors for exacerbation vary by season. Thus information on individual patients might be beneficial in strategies to prevent these seasonal events. C1 [Teach, Stephen J.] Childrens Natl Hlth Syst, Washington, DC 20010 USA. [Teach, Stephen J.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Gergen, Peter J.] NIAID, Bethesda, MD 20892 USA. [Szefler, Stanley J.] Childrens Hosp Colorado, Aurora, CO USA. [Szefler, Stanley J.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Mitchell, Herman E.; Calatroni, Agustin; Wildfire, Jeremy] Rho Fed Syst Div, Chapel Hill, NC USA. [Bloomberg, Gordon R.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Kercsmar, Carolyn M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA. [Liu, Andrew H.] Univ Colorado, Childrens Hosp Colorado, Sch Med, Aurora, CO USA. [Makhija, Melanie M.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Matsui, Elizabeth] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Morgan, Wayne] Univ Arizona, Coll Med, Tucson, AZ USA. [O'Connor, George] Boston Univ, Sch Med, Boston, MA 02118 USA. [Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Teach, SJ (reprint author), Childrens Natl Hlth Syst, 111 Michigan Ave NW, Washington, DC 20010 USA. EM steach@childrensnational.org FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [NO1-AI-25496, NO1-AI-25482, HHSN272200900052C, HHSN272201000052I]; National Center for Research Resources, National Institutes of Health [RR00052, M01RR00533, UL1 RR024982, M01RR00071, 5M01RR020359-04, 1UL1RR025771, 1UL1RR025780, 1UL1RR024156, UL1RR031988, UL1RR025741, UL1TR000451] FX This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract nos. NO1-AI-25496, NO1-AI-25482, HHSN272200900052C, and HHSN272201000052I. Additional support was provided by the National Center for Research Resources, National Institutes of Health, under grants RR00052, M01RR00533, UL1 RR024982, M01RR00071, 5M01RR020359-04, 1UL1RR025771, 1UL1RR025780, 1UL1RR024156, UL1RR031988, UL1RR025741, and UL1TR000451. Lincoln Diagnostics provided the Multi-Test, and GlaxoSmithKline (GSK) provided study drug for Asthma Control Evaluation study participants. Novartis Pharmaceuticals provided study drug under a clinical trial agreement with the University of Wisconsin-Madison, Dey Pharma provided EpiPens, and SC Johnson provided household pest control for Inner City Anti-IgE Therapy for Asthma study participants. None of these companies had a role in the development or approval of the protocol, conduct of the trial, data analysis, manuscript preparation, or the decision to submit for publication. NR 34 TC 29 Z9 29 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2015 VL 135 IS 6 BP 1465 EP U116 DI 10.1016/j.jaci.2014.12.1942 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA CK0ZC UT WOS:000355933400008 PM 25794658 ER PT J AU Pino-Yanes, M Gignoux, CR Galanter, JM Levin, AM Campbell, CD Eng, C Huntsman, S Nishimura, KK Gourraud, PA Mohajeri, K O'Roak, BJ Hu, DL Mathias, RA Nguyen, EA Roth, LA Padhukasahasram, B Moreno-Estrada, A Sandoval, K Winkler, CA Lurmann, F Davis, A Farber, HJ Meade, K Avila, PC Serebrisky, D Chapela, R Ford, JG Lenoir, MA Thyne, SM Brigino-Buenaventura, E Borrell, LN Rodriguez-Cintron, W Sen, S Kumar, R Rodriguez-Santana, JR Bustamante, CD Martinez, FD Raby, BA Weiss, ST Nicolae, DL Ober, C Meyers, DA Bleecker, ER Mack, SJ Hernandez, RD Eichler, EE Barnes, KC Williams, LK Torgerson, DG Burchard, EG AF Pino-Yanes, Maria Gignoux, Christopher R. Galanter, Joshua M. Levin, Albert M. Campbell, Catarina D. Eng, Celeste Huntsman, Scott Nishimura, Katherine K. Gourraud, Pierre-Antoine Mohajeri, Kiana O'Roak, Brian J. Hu, Donglei Mathias, Rasika A. Nguyen, Elizabeth A. Roth, Lindsey A. Padhukasahasram, Badri Moreno-Estrada, Andres Sandoval, Karla Winkler, Cheryl A. Lurmann, Fred Davis, Adam Farber, Harold J. Meade, Kelley Avila, Pedro C. Serebrisky, Denise Chapela, Rocio Ford, Jean G. Lenoir, Michael A. Thyne, Shannon M. Brigino-Buenaventura, Emerita Borrell, Luisa N. Rodriguez-Cintron, William Sen, Saunak Kumar, Rajesh Rodriguez-Santana, Jose R. Bustamante, Carlos D. Martinez, Fernando D. Raby, Benjamin A. Weiss, Scott T. Nicolae, Dan L. Ober, Carole Meyers, Deborah A. Bleecker, Eugene R. Mack, Steven J. Hernandez, Ryan D. Eichler, Evan E. Barnes, Kathleen C. Williams, L. Keoki Torgerson, Dara G. Burchard, Esteban G. TI Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE IgE; genome-wide association study; admixture mapping; allergy; asthma; next-generation sequencing; Latinos; Hispanics; minority populations ID DNA-SEQUENCING DATA; ATOPIC-DERMATITIS; AFRICAN-AMERICAN; SUSCEPTIBILITY LOCI; ALLERGIC DISEASE; IMMUNOGLOBULIN-E; GENETIC-ANALYSIS; ASTHMA; POPULATION; ANCESTRY AB Background: IgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders. Objective: We sought to identify genetic variants associated with IgE levels in Latinos. Methods: We performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies. Results: We confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of a polymorphism in the zinc finger protein 365 gene (ZNF365) with total IgE levels (rs200076616, P = 2.3 x 10(-8)). We next identified 4 admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) at which local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower IgE levels (P = 4.95 x 10(-8)). All but 22q13.1 were replicated in an independent sample of Latinos, and 2 of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified 6 genome-wide significant single nucleotide polymorphisms in Latinos, 2 of which replicated in European Americans. Another single nucleotide polymorphism was peak-wide significant within 14q23.2 in African Americans (rs1741099, P = 3.7 x 10(-6)) and replicated in non-African American samples (P = .011). Conclusion: We confirmed genetic associations at 6 genes and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse multiethnic populations to uncover novel loci associated with total IgE levels. C1 [Pino-Yanes, Maria; Gignoux, Christopher R.; Galanter, Joshua M.; Eng, Celeste; Huntsman, Scott; Nishimura, Katherine K.; Hu, Donglei; Nguyen, Elizabeth A.; Roth, Lindsey A.; Torgerson, Dara G.; Burchard, Esteban G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Gignoux, Christopher R.; Galanter, Joshua M.; Hernandez, Ryan D.; Burchard, Esteban G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Sen, Saunak] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Pino-Yanes, Maria] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Gignoux, Christopher R.; Moreno-Estrada, Andres; Sandoval, Karla; Bustamante, Carlos D.] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA. [Levin, Albert M.] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA. [Padhukasahasram, Badri; Williams, L. Keoki] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA. [Williams, L. Keoki] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA. [Campbell, Catarina D.; Mohajeri, Kiana; O'Roak, Brian J.; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Gourraud, Pierre-Antoine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [O'Roak, Brian J.] Oregon Hlth & Sci Univ, Mol & Med Genet Dept, Portland, OR 97201 USA. [Mathias, Rasika A.; Barnes, Kathleen C.] Johns Hopkins Univ, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD USA. [Winkler, Cheryl A.] NCI, Basic Res Lab, Ctr Canc Res, Leidos Biomed,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Lurmann, Fred] Sonoma Technol, Petaluma, NC USA. [Davis, Adam; Meade, Kelley] Childrens Hosp & Res Ctr Oakland, Houston, TX USA. [Farber, Harold J.] Baylor Coll Med, Dept Pediat, Sect Pulmonol, Houston, TX 77030 USA. [Farber, Harold J.] Texas Childrens Hosp, Houston, TX 77030 USA. [Avila, Pedro C.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Kumar, Rajesh] Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Serebrisky, Denise] Jacobi Med Ctr, Pediat Pulm Div, Bronx, NY USA. [Chapela, Rocio] INER, Mexico City, DF, Mexico. [Ford, Jean G.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Lenoir, Michael A.] Bay Area Pediat, Oakland, CA USA. [Thyne, Shannon M.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Pediat, San Francisco, CA 94143 USA. [Brigino-Buenaventura, Emerita] Kaiser Permanente Vallejo Med Ctr, Dept Allergy & Immunol, Vallejo, CA USA. [Borrell, Luisa N.] CUNY, Grad Program Publ Hlth, Dept Hlth Sci, Bronx, NY USA. [Rodriguez-Cintron, William] Vet Caribbean Hlth Care Syst, San Juan, PR USA. [Rodriguez-Santana, Jose R.] Ctr Neumol Pediat, San Juan, PR USA. [Martinez, Fernando D.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA. [Martinez, Fernando D.] Univ Arizona, Inst BIO5, Tucson, AZ USA. [Raby, Benjamin A.; Weiss, Scott T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Charming Div Network Med,Dept Med, Boston, MA 02115 USA. [Nicolae, Dan L.; Ober, Carole] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Meyers, Deborah A.; Bleecker, Eugene R.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA. [Mack, Steven J.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA USA. RP Pino-Yanes, M (reprint author), Univ Calif San Francisco, Dept Med, 1550 4th St,Rock Hall Rm 582,UCSF Box 2911, San Francisco, CA 94143 USA. EM mdelpino@ull.edu.es RI Gourraud, Pierre-Antoine/O-3024-2015; Pino-Yanes, Maria/C-8498-2017; OI Pino-Yanes, Maria/0000-0003-0332-437X; O'Roak, Brian/0000-0002-4141-0095; Nguyen, Elizabeth/0000-0002-8070-6382 FU NCATS NIH HHS [KL2 TR000143, KL2TR000143, UL1 TR000430]; NCRR NIH HHS [M01 RR000188, M01-RR00188]; NHLBI NIH HHS [HL075419, HL004464, HL066289, HL078885, HL083069, HL087680, HL088133, HL093023, HL101543, HL101651, HL104608, HL111636, HL117004, HL65899, K23 HL004464, K23 HL093023, K23 HL111636, P01 HL083069, R01 HL066289, R01 HL078885, R01 HL087680, R01 HL088133, R01 HL104608, R01 HL117004, R37 HL066289, RC2 HL101543, RC2 HL101651, U01 HL065899, U01 HL075419]; NIAID NIH HHS [AI061774, AI079139, R01 AI061774, R01 AI079139, U19 AI095230]; NIEHS NIH HHS [ES015794, R01 ES015794]; NIGMS NIH HHS [GM007175, GM007546, T32 GM007175, T32 GM007546]; NIMHD NIH HHS [MD006902, P60 MD006902]; PHS HHS [HHSN26120080001E] NR 53 TC 7 Z9 7 U1 0 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2015 VL 135 IS 6 BP 1502 EP 1510 DI 10.1016/j.jaci.2014.10.033 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA CK0ZC UT WOS:000355933400013 PM 25488688 ER PT J AU Lanternier, F Mandaviani, SA Barbati, E Chaussade, H Koumar, Y Levy, R Denis, B Brunel, AS Martin, S Loop, M Peeters, J de Selys, A Vanclaire, J Vermylen, C Nassogne, MC Chatzis, O Liu, LY Migaud, M Pedergnana, V Desoubeaux, G Jouvion, G Chretien, F Darazam, IA Schaffer, AA Netea, MG De Bruycker, JJ Bernard, L Reynes, J Amazrine, N Abel, L Van der Linden, D Harrison, T Picard, C Lortholary, O Mansouri, D Casanova, JL Puel, A AF Lanternier, Fanny Mandaviani, Seyed Alireza Barbati, Elisa Chaussade, Helene Koumar, Yatrika Levy, Romain Denis, Blandine Brunel, Anne-Sophie Martin, Sophie Loop, Michele Peeters, Julie de Selys, Ariel Vanclaire, Jean Vermylen, Christiane Nassogne, Marie-Cecile Chatzis, Olga Liu, Luyan Migaud, Melanie Pedergnana, Vincent Desoubeaux, Guillaume Jouvion, Gregory Chretien, Fabrice Darazam, Ilad Alavi Schaeffer, Alejandro A. Netea, Mihai G. De Bruycker, Jean J. Bernard, Louis Reynes, Jacques Amazrine, Noureddine Abel, Laurent Van der Linden, Dimitri Harrison, Tom Picard, Capucine Lortholary, Olivier Mansouri, Davood Casanova, Jean-Laurent Puel, Anne TI Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, or both SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Inborn error of immunity; primary immunodeficiency; invasive fungal diseases; inherited CARD9 deficiency; central nervous system; colitis; Candida species; human ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; HYPER-IGE SYNDROME; CHRONIC GRANULOMATOUS-DISEASE; CENTRAL-NERVOUS-SYSTEM; FUNGAL-INFECTIONS; CEREBRAL CANDIDIASIS; CEREBROSPINAL-FLUID; IL-17 IMMUNITY; INBORN-ERRORS; MASS LESION AB Background: Invasive infections of the central nervous system (CNS) or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningoencephalitis, colitis, or both caused by Candida species remain unexplained. Objective: We studied 5 previously healthy children and adults with unexplained invasive disease of the CNS, digestive tract, or both caused by Candida species. The patients were aged 39, 7, 17, 37, and 26 years at the time of infection and were unrelated, but each was born to consanguineous parents of Turkish (2 patients), Iranian, Moroccan, or Pakistani origin. Meningoencephalitis was reported in 3 patients, meningoencephalitis associated with colitis was reported in a fourth patient, and the fifth patient had colitis only. Methods: Inherited caspase recruitment domain family, member 9 (CARD9) deficiency was recently reported in otherwise healthy patients with other forms of severe disease caused by Candida, Trichophyton, Phialophora, and Exophiala species, including meningoencephalitis but not colitis caused by Candida and Exophiala species. Therefore we sequenced CARD9 in the 5 patients. Results: All patients were found to be homozygous for rare and deleterious mutant CARD9 alleles: R7OW and Q289* for the 3 patients with Candida albicans induced meningoencephalitis, R35Q for the patient with meningoencephalitis and colitis caused by Candida glabrata, and Q295* for the patient with Candida albicans induced colitis. Regardless of their levels of mutant CARD9 protein, the patients' monocyte-derived dendritic cells responded poorly to CARD9-dependent fungal agonists (curdlan, heat-killed Calbicans, Saccharomyces cerevisiae, and Exophiala dermatitidis). Conclusion: Invasive infections of the CNS or digestive tract caused by Candida species in previously healthy children and even adults might be caused by inherited CARD9 deficiency. C1 [Lanternier, Fanny; Barbati, Elisa; Levy, Romain; Liu, Luyan; Migaud, Melanie; Pedergnana, Vincent; Abel, Laurent; Picard, Capucine; Casanova, Jean-Laurent; Puel, Anne] INSERM, UMR 1163, Lab Human Genet Infect Dis, Necker Branch, Paris, France. [Lanternier, Fanny; Barbati, Elisa; Levy, Romain; Denis, Blandine; Liu, Luyan; Migaud, Melanie; Pedergnana, Vincent; Abel, Laurent; Picard, Capucine; Lortholary, Olivier; Casanova, Jean-Laurent; Puel, Anne] Univ Paris 05, Imagine Inst, F-75015 Paris, France. [Lanternier, Fanny; Denis, Blandine; Lortholary, Olivier] Hop Necker Enfants Malad, AP HP, Necker Pasteur Infect Dis Ctr, Imagine Inst, Paris, France. [Mandaviani, Seyed Alireza] NRITLD, Pediat Resp Dis Res Ctr, Tehran, Iran. [Darazam, Ilad Alavi; Mansouri, Davood] Shahid Beheshti Univ Med Sci, Masih Daneshvari Hosp, Natl Res Inst TB & Lung Dis, Dept Clin Immunol & Allergy, Tehran, Iran. [Chaussade, Helene; Bernard, Louis] Bretonneau Hosp, Infect Dis Unit, Tours, France. [Koumar, Yatrika; Brunel, Anne-Sophie; Reynes, Jacques] Infect Dis Unit, Montpellier, France. [Martin, Sophie; Peeters, Julie; Chatzis, Olga; Van der Linden, Dimitri] UCL, St Luc Univ Hosp, Pediat Infect Dis Unit, Brussels, Belgium. [Vermylen, Christiane] UCL, St Luc Univ Hosp, Pediat Hematol Oncol Unit, Brussels, Belgium. [Nassogne, Marie-Cecile] UCL, St Luc Univ Hosp, Pediat Neurol Unit, Brussels, Belgium. [Loop, Michele; de Selys, Ariel; Vanclaire, Jean] St Jean Hosp, Pediat Neonatol Unit, Brussels, Belgium. [Desoubeaux, Guillaume] Bretonneau Hosp, Ctr Study Resp Dis, Parasitol Mycol Trop Med Unit, INSERM,U1100,Equipe 3,Sch Med, Tours, France. [Jouvion, Gregory; Chretien, Fabrice] Inst Pasteur, Human Histopathol & Anim Models, Infect & Epidemiol Dept, Paris, France. [Lortholary, Olivier] Inst Pasteur, Mol Mycol Unit, Natl Reference Ctr Invas Mycoses & Antifungals, Paris, France. [Chretien, Fabrice] Hop St Anne, Neuropathol Lab, F-75674 Paris, France. [Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands. [Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, NL-6525 ED Nijmegen, Netherlands. [De Bruycker, Jean J.] Hop St Justine, Univ Ctr, Immunol & Rheumatol Unit, Montreal, PQ H3T 1C5, Canada. [Amazrine, Noureddine] Dept Neurosurg, Tangier, Morocco. [Abel, Laurent; Casanova, Jean-Laurent] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10021 USA. [Harrison, Tom] St Georges Univ London, Infect & Immun Res Inst, London, England. [Picard, Capucine] Hop Necker Enfants Malad, AP HP, Study Ctr Immunodeficiency, Paris, France. [Picard, Capucine; Casanova, Jean-Laurent] Hop Necker Enfants Malad, AP HP, Pediat Hematol Immunol Unit, Paris, France. [Casanova, Jean-Laurent] Howard Hughes Med Inst, New York, NY USA. RP Puel, A (reprint author), Univ Paris 05, Sorbonne Paris Cite, Lab Human Genet Infect Dis, Necker Branch,INSERM,UMR 1163,Imagine Inst, 24 Blvd Montparnasse, F-75015 Paris, France. EM anne.puel@inserm.fr RI Netea, Mihai/N-5155-2014; DESOUBEAUX, Guillaume/J-5026-2015; OI DESOUBEAUX, Guillaume/0000-0001-7945-9890; mahdaviani, alireza/0000-0001-6224-4797; mansouri, davood/0000-0002-0564-8282 FU Rockefeller University; INSERM; Paris Descartes University; St. Giles Foundation; l'Agence Nationale de la Recherche [11-BSV3-005-01]; Jeffrey Modal Foundation; French Government, Investissement d' Avenir program, Laboratoire d' Excellence "Integrative Biology of Emerging Infectious Diseases" [ANR-10-LABX-62-IBEID]; CMIT (French Faculties College of Infectious Diseases) FX Supported in part by the Rockefeller University, INSERM, Paris Descartes University, the St. Giles Foundation and l'Agence Nationale de la Recherche (grant GENCMCD no 11-BSV3-005-01 to A.P.), and a Translational Research grant from the Jeffrey Modal Foundation (to A.P.). This study also received funding from the French Government as part of the Investissement d' Avenir program, Laboratoire d' Excellence "Integrative Biology of Emerging Infectious Diseases" (grant no. ANR-10-LABX-62-IBEID). F.L. was supported by a grant from the CMIT (French Faculties College of Infectious Diseases) and INSERM. NR 70 TC 20 Z9 20 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2015 VL 135 IS 6 BP 1558 EP U269 DI 10.1016/j.jaci.2014.12.1930 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA CK0ZC UT WOS:000355933400019 PM 25702837 ER PT J AU Tesi, B Sieni, E Neves, C Romano, F Cetica, V Cordeiro, AI Chiang, S Schlums, H Galli, L Avenali, S Tondo, A Canessa, C Henter, JI Nordenskjold, M Hsu, AP Holland, SM Neves, JE Azzari, C Bryceson, YT AF Tesi, Bianca Sieni, Elena Neves, Conceiceto Romano, Francesca Cetica, Valentina Cordeiro, Ana Isabel Chiang, Samuel Schlums, Heinrich Galli, Luisa Avenali, Stefano Tondo, Annalisa Canessa, Clementina Henter, Jan-Inge Nordenskjold, Magnus Hsu, Amy P. Holland, Steven M. Neves, Joeto E. Azzari, Chiara Bryceson, Yenan T. TI Hemophagocytic lymphohistiocytosis in 2 patients with underlying IFN-gamma receptor deficiency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID INTERFERON-GAMMA; INFLAMMATION; PERFORIN; IMMUNITY; ANEMIA; MICE C1 [Tesi, Bianca; Henter, Jan-Inge] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden. [Tesi, Bianca; Nordenskjold, Magnus] Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Clin Genet Unit, Stockholm, Sweden. [Tesi, Bianca; Nordenskjold, Magnus] Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. [Sieni, Elena; Tondo, Annalisa] Anna Meyer Childrens Univ Hosp, Dept Pediat Hematol Oncol, Florence, Italy. [Neves, Conceiceto; Cordeiro, Ana Isabel; Neves, Joeto E.] Pediat Univ Hosp, Hosp Dona Estefania, Primary Immunodeficiencies Unit, Lisbon, Portugal. [Neves, Conceiceto; Cordeiro, Ana Isabel; Neves, Joeto E.] NOVA Med Sch, Chron Dis Res Ctr, CEDOC, Lisbon, Portugal. [Romano, Francesca; Canessa, Clementina; Azzari, Chiara] Univ Florence, Dept Pediat Immunol, Florence, Italy. [Romano, Francesca; Canessa, Clementina; Azzari, Chiara] Anna Meyer Childrens Univ Hosp, Jeffrey Modell Ctr Primary Immunodeficiencies, Florence, Italy. [Chiang, Samuel; Schlums, Heinrich] Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, Ctr Infect Med, Stockholm, Sweden. [Galli, Luisa] Anna Meyer Childrens Univ Hosp, Dept Pediat Infect Dis, Florence, Italy. [Avenali, Stefano] Anna Meyer Childrens Univ Hosp, Dept Pediat Intens Care, Florence, Italy. [Hsu, Amy P.; Holland, Steven M.] NIAID, NIH, Bethesda, MD 20892 USA. [Bryceson, Yenan T.] Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, N-5020 Bergen, Norway. RP Tesi, B (reprint author), Karolinska Univ Hosp Solna, Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden. EM Yenan.Bryceson@ki.se RI chiang, samuel/M-9267-2016; Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013; OI Nordenskjold, Magnus/0000-0002-4974-425X NR 15 TC 10 Z9 10 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2015 VL 135 IS 6 BP 1638 EP 1641 DI 10.1016/j.jaci.2014.11.030 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA CK0ZC UT WOS:000355933400028 PM 25592983 ER PT J AU Lee, J Miller, BT Damjanovic, A Brooks, BR AF Lee, Juyong Miller, Benjamin T. Damjanovic, Ana Brooks, Bernard R. TI Enhancing Constant-pH Simulation in Explicit Solvent with a Two-Dimensional Replica Exchange Method SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID FREE-ENERGY CALCULATIONS; MOLECULAR-DYNAMICS SIMULATIONS; DISCRETE PROTONATION STATES; LIGAND BINDING STRUCTURES; GUIDED LANGEVIN DYNAMICS; MONTE-CARLO; STRUCTURE RESERVOIR; WATER PENETRATION; LAMBDA-DYNAMICS; INTERNAL GROUPS AB We present a new method for enhanced sampling for constant-pH simulations in explicit water based on a two-dimensional (2D) replica exchange scheme. The new method is a significant extension of our previously developed constant-pH simulation method, which is based on enveloping distribution sampling (EDS) coupled with a one-dimensional (1D) Hamiltonian exchange method (HREM). EDS constructs a hybrid Hamiltonian from multiple discrete end state Hamiltonians that, in this case, represent different protonation states of the system. The ruggedness and heights of the hybrid Hamiltonian's energy barriers can be tuned by the smoothness parameter. Within the context of the ID EDS-HREM method, exchanges are performed between replicas with different smoothness parameters, allowing frequent protonation-state transitions and sampling of conformations that are favored by the end-state Hamiltonians. In this work, the 1D method is extended to 2D with an additional dimension, external pH. Within the context of the 2D method (2D EDS-HREM), exchanges are performed on a lattice of Hamiltonians with different pH conditions and smoothness parameters. We demonstrate that both the 1D and 2D methods exactly reproduce the thermodynamic properties of the semigrand canonical (SGC) ensemble of a system at a given pH. We have tested our new 2D method on aspartic acid, glutamic acid, lysine, a four residue peptide (sequence KAAE), and snake cardiotoxin. In all cases, the 2D method converges faster and without loss of precision; the only limitation is a loss of flexibility in how CPU time is employed. The results for snake cardiotoxin demonstrate that the 2D method enhances protonation-state transitions, samples a wider conformational space with the same amount of computational resources, and converges significantly faster overall than the original 1D method. C1 [Lee, Juyong; Miller, Benjamin T.; Damjanovic, Ana; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Damjanovic, Ana] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA. RP Lee, J (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM juyong.lee@nih.gov RI Lee, Juyong/A-7869-2013 OI Lee, Juyong/0000-0003-1174-4358 FU Intramural Research Program of the National Heart, Lung, and Blood Institute, NIH FX This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, NIH. NR 92 TC 12 Z9 12 U1 5 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 EI 1549-9626 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD JUN PY 2015 VL 11 IS 6 BP 2560 EP 2574 DI 10.1021/ct501101f PG 15 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA CK4NY UT WOS:000356201700017 PM 26575555 ER PT J AU Farhat, T Iannotti, RJ Summersett-Ringgold, F AF Farhat, Tilda Iannotti, Ronald J. Summersett-Ringgold, Faith TI Weight, Weight Perceptions, and Health-Related Quality of Life Among a National Sample of US Girls SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article ID SCHOOL-AGED CHILDREN; OBESE CHILDREN; RISK BEHAVIORS; MENTAL-HEALTH; UNITED-STATES; ADOLESCENTS; OVERWEIGHT; PREVALENCE; BMI; DISCRIMINATION AB Objective: To examine associations between 3 weight indices (weight status, perceived weight, and weight status perception accuracy) and heath-related quality of life (HRQOL). Methods: Data are for girls in the 2009 Health Behaviors in School-Age Children survey, a nationally representative sample of students in Grades 5 to 10 during the 2009/2010 school year (n = 5018). Controlling for sociodemographics, multivariate linear regressions examined associations between self-reported weight status (underweight/normal/overweight/obese), perceived weight (how children categorize their weight), weight status perception accuracy (underestimate/accurate perception/overestimate), and dimensions of HRQOL, including physical, emotional, social, and school functioning. Results: Although obesity was only associated with poor physical and emotional HRQOL, perceptions of being overweight were associated with worse physical, emotional, school, and social HRQOL. Furthermore, girls who overestimated their weight reported poorer HRQOL than those with accurate weight perceptions. Associations of perceptions of being overweight and weight status overestimation with poor HRQOL despite, in most instances, the absence of associations between weight status and HRQOL suggest that weight status perceptions may not merely be a mediator of a weight status-HRQOL association but a significant independent correlate of poor HRQOL. Conclusion: These findings raise the issue of whether there is a need to prioritize intervention efforts to promote better HRQOL by redefining the population of girls most at risk. Parents, teachers, and clinicians should be aware that, rather than overweight status, perceptions of being overweight (accurately or not) are associated with a poor HRQOL among girls. Future research should examine the potential negative effect of using specific body image terminologies on adolescents' psychological health. C1 [Farhat, Tilda] Natl Inst Minor Hlth & Hlth Dispar, Off Sci Policy Planning Anal & Reporting, NIH, Bethesda, MD 20892 USA. [Iannotti, Ronald J.] Univ Massachusetts, Dept Exercise & Hlth Sci, Boston, MA 02125 USA. [Summersett-Ringgold, Faith] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Mental Hlth Serv & Policy Program, Chicago, IL 60611 USA. [Farhat, Tilda; Iannotti, Ronald J.; Summersett-Ringgold, Faith] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA. RP Farhat, T (reprint author), Natl Inst Minor Hlth & Hlth Dispar, Off Sci Policy Planning Anal & Reporting, NIH, 6707 Democracy Blvd,Suite 200, Bethesda, MD 20892 USA. EM farhatti@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-5-3401]; Maternal and Child Health Bureau of the Health Resources and Services Administration FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract N01-HD-5-3401) and by the Maternal and Child Health Bureau of the Health Resources and Services Administration. NR 42 TC 2 Z9 2 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 2015 VL 36 IS 5 BP 313 EP 323 DI 10.1097/DBP.0000000000000172 PG 11 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA CK5FM UT WOS:000356248100002 PM 25961900 ER PT J AU Lee, JH Shao, S Cheng, KT Lovell, JF Paik, CH AF Lee, Jae-Ho Shao, Shuai Cheng, Kenneth T. Lovell, Jonathan F. Paik, Chang H. TI Tc-99m-labeled porphyrin-lipid nanovesicles SO JOURNAL OF LIPOSOME RESEARCH LA English DT Article DE Drug-encapsulated liposome; nanotechnology; size exclusion analysis; sustained release; Tc-99m-labeled porphyrin-lipid nanovesicles ID AMIKACIN-LOADED LIPOSOMES; GAMMA-SCINTIGRAPHY; LUNG; THERAPY; AGENTS; TUMORS; ACTIVATION; DEPOSITION; CLEARANCE; DELIVERY AB Porphyrin-lipid nanovesicles (PLN) have been developed with intrinsic capabilities as activatable multimodal photonic contrast agents. Radio labeling of PLN encapsulating drugs could eventually be able to provide quantitative in vivo information for diagnosing and treating diseases. In this study, we developed Tc-99m-labeled porphyrin-lipid nanovesicles (Tc-99m-PLN) as a cargo-encapsulated formulation without significant impact on liposome integrity and encapsulation stability. 50 mM calcein was encapsulated into PLN by probe sonication. The size of the PLN was about 150 nm. The PLN were then reacted with Tc-99m using SnCl2 dissolved in 1 mM HCl as a reducing agent and incubated for 10 min at 22 degrees C. The radiolabeling efficiency and stability of Tc-99m-PLN were evaluated by instant thin-layer chromatography and low-pressure liquid chromatography (LPLC). Tc-99m labeling was successful with a >92% labeling efficiency. LPLC showed that the liposomal elution peaks of the porphyrin-lipid and the calcein overlapped with the radioactivity elution peak of Tc-99m-labeled PLN. The Tc-99m-labeling procedure did not change the size of PLN. Encapsulated calcein remained inert inside PLN. Thus, this work lays out a simple and effective radiolabeling method using SnCl2 in HCI in the preparation of Tc-99m-PLN. C1 [Lee, Jae-Ho; Cheng, Kenneth T.; Paik, Chang H.] NIH, Radiopharmaceut Lab, Div Nucl Med, Dept Radiol & Imaging Sci,Warren G Magnuson Clin, Bethesda, MD 20892 USA. [Shao, Shuai; Lovell, Jonathan F.] SUNY Buffalo, Dept Biomed Engn, Buffalo, NY 14260 USA. RP Lee, JH (reprint author), NIH, Radiopharmaceut Lab, Div Nucl Med, Dept Radiol & Imaging Sci,Warren G Magnuson Clin, Bldg 10, Bethesda, MD 20892 USA. EM leejaeho@mail.nih.gov FU intramural research program of Clinical Center, NIH FX The authors report no declaration of interest. This research was supported by the intramural research program of Clinical Center, NIH. NR 25 TC 10 Z9 10 U1 3 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0898-2104 EI 1532-2394 J9 J LIPOSOME RES JI J. Liposome Res. PD JUN PY 2015 VL 25 IS 2 BP 101 EP 106 DI 10.3109/08982104.2014.932379 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA CK4QJ UT WOS:000356208000002 PM 24963601 ER PT J AU Lowenthal, MS Markey, SP Dosemeci, A AF Lowenthal, Mark S. Markey, Sanford P. Dosemeci, Ayse TI Quantitative Mass Spectrometry Measurements Reveal Stoichiometry of Principal Postsynaptic Density Proteins SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE postsynaptic density; protein stoichiometry; multiple reaction monitoring; copy numbers ID AMPA RECEPTOR EXPRESSION; ACTIVITY-DEPENDENT UBIQUITINATION; EXCITATORY SYNAPSES; KINASE-II; ABSOLUTE QUANTIFICATION; LOCALIZATION PATTERNS; SYNAPTIC PLASTICITY; TARGETED PROTEOMICS; CEREBRAL-CORTEX; RAT FOREBRAIN AB Quantitative studies are presented of postsynaptic density (PSD) fractions from rat cerebral cortex with the ultimate goal of defining the average copy numbers of proteins in the PSD complex. Highly specific and selective isotope dilution mass spectrometry assays were developed using isotopically labeled polypeptide concatemer internal standards. Interpretation of PSD protein stoichiometry was achieved as a molar ratio with respect to PSD-95 (SAP-90, DLG4), and subsequently, copy numbers were estimated using a consensus literature value for PSD-95. Average copy numbers for several proteins at the PSD were estimated for the first time, including those for AIDA-1, BRAGs, and densin. Major findings include evidence for the high copy number of AIDA-1 in the PSD (144 +/- 30)-equivalent to that of the total GKAP family of proteins (150 +/- 27)-suggesting that AIDA-I is an element of the PSD scaffold. The average copy numbers for NMDA receptor sub-units were estimated to be 66 +/- 18, 27 +/- 9, and 45 +/- 15, respectively, for GluN1, GluN2A, and GluN2B, yielding a total of 34 10 NMDA channels. Estimated average copy numbers for AMPA channels and their auxiliary sub-units TARPs were 68 +/- 36 and 144 +/- 38, respectively, with a stoichiometry of similar to 1:2 supporting the assertion that most AMPA receptors anchor to the PSD via TARP sub-units. This robust, quantitative analysis of PSD proteins improves upon and extends the list of major PSD components with assigned average copy numbers in the ongoing effort to unravel the complex molecular architecture of the PSD. C1 [Lowenthal, Mark S.; Markey, Sanford P.] NIST, Biomol Measurement Div, Gaithersburg, MD 20899 USA. [Markey, Sanford P.] NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. [Dosemeci, Ayse] Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Lowenthal, MS (reprint author), NIST, Biomol Measurement Div, Gaithersburg, MD 20899 USA. EM mark.lowenthal@nist.gov FU National Institute of Neurological Diseases and Stroke; National Institute of Mental Health [1ZIAMH000274-35] FX Our thanks to Dhaval Nanavati, Adele Blackler, Jim Makusky, Brian Martin, and Jacqui Cole, who worked on earlier stages of this project, Deb Chatterjee of the NCI Protein Expression Laboratory for production of fused labeled polypeptides, and Dr. Thomas Reese for a critical reading of the manuscript. This research was supported by the Intramural Research Programs of the National Institute of Neurological Diseases and Stroke and the National Institute of Mental Health, project 1ZIAMH000274-35. NR 73 TC 12 Z9 12 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD JUN PY 2015 VL 14 IS 6 BP 2528 EP 2538 DI 10.1021/acs.jproteome.5b00109 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CK1IW UT WOS:000355962000015 PM 25874902 ER PT J AU Marabini, R Carragher, B Chen, SX Chen, J Cheng, AC Downing, KH Frank, J Grassucci, RA Heymann, JB Jiang, W Jonic, S Liao, HY Ludtke, SJ Patwari, S Piotrowski, AL Quintana, A Sorzano, COS Stahlberg, H Vargas, J Voss, NR Chiu, W Carazo, JM AF Marabini, Roberto Carragher, Bridget Chen, Shaoxia Chen, James Cheng, Anchi Downing, Kenneth H. Frank, Joachim Grassucci, Robert A. Heymann, J. Bernard Jiang, Wen Jonic, Slavica Liao, Hstau Y. Ludtke, Steven J. Patwari, Shail Piotrowski, Angela L. Quintana, Adrian Sorzano, Carlos O. S. Stahlberg, Henning Vargas, Javier Voss, Neil R. Chiu, Wah Carazo, Jose M. TI CTF Challenge: Result summary SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Electron microscopy; Contrast transfer function; High-resolution; Benchmarking; Challenge AB Image formation in bright field electron microscopy can be described with the help of the contrast transfer function (CTF). In this work the authors describe the "CTF Estimation Challenge", called by the Madrid Instruct Image Processing Center (I2PC) in collaboration with the National Center for Macromolecular Imaging (NCMI) at Houston. Correcting for the effects of the CTF requires accurate knowledge of the CTF parameters, but these have often been difficult to determine. In this challenge, researchers have had the opportunity to test their ability in estimating some of the key parameters of the electron microscope CTF on a large micrograph data set produced by well-known laboratories on a wide set of experimental conditions. This work presents the first analysis of the results of the CTF Estimation Challenge, including an assessment of the performance of the different software packages under different conditions, so as to identify those areas of research where further developments would be desirable in order to achieve high-resolution structural information. (C) 2015 Elsevier Inc. All rights reserved. C1 [Marabini, Roberto] Univ Autonoma Madrid, Escuela Politecn Super, E-28049 Madrid, Spain. [Carragher, Bridget; Cheng, Anchi] Scripps Res Inst, Natl Resource Automated Mol Microscopy, La Jolla, CA 92037 USA. [Ludtke, Steven J.; Chiu, Wah] Baylor Coll Med, Houston, TX 77030 USA. [Downing, Kenneth H.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. [Frank, Joachim; Grassucci, Robert A.; Liao, Hstau Y.] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. [Jiang, Wen] Purdue Univ, Biol Sci, W Lafayette, IN 47907 USA. [Quintana, Adrian; Sorzano, Carlos O. S.; Vargas, Javier; Carazo, Jose M.] CSIC, Natl Biotechnol Ctr, Biocomp Unit, E-28049 Madrid, Spain. [Stahlberg, Henning] Univ Basel, Biozentrum, CH-4058 Basel, Switzerland. [Chen, Shaoxia] MRC LMB, Cambridge CB2 0QH, England. [Jonic, Slavica] Univ Paris 06, Sorbonne Univ, CNRS UMR 7590, IMPMC,MNHN,IRD UMR 206, F-75005 Paris, France. [Patwari, Shail; Piotrowski, Angela L.; Voss, Neil R.] Roosevelt Univ, Dept Biol Chem & Phys Sci, Schaumburg, IL 60173 USA. [Heymann, J. Bernard] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. [Chen, James] MIT, Cambridge, MA 02139 USA. RP Marabini, R (reprint author), Univ Autonoma Madrid, Escuela Politecn Super, E-28049 Madrid, Spain. EM roberto@cnb.csic.es RI Voss, Neil/K-6244-2012; Vargas, Javier/L-5546-2015; S. Sorzano, Carlos Oscar/F-2639-2016; Stahlberg, Henning/H-1868-2011; OI S. Sorzano, Carlos Oscar/0000-0002-9473-283X; Stahlberg, Henning/0000-0002-1185-4592; Jonic, Slavica/0000-0001-5112-2743; Marabini, Roberto/0000-0001-7876-1684 FU Spanish Ministry of Economy and Competitiveness [AIC-A-2011-0638, BIO2013-44647-R, BFU2013-41249-P]; Comunidad de Madrid through grant CAM [S2010/BMD-2305]; NSF [1114901]; NRAMM [GM103310]; Ramon y Cajal fellowship; Juan de la Cierva fellowship [JCI-2011-10185]; Instruct part of the European Strategy Forum on Research Infrastructures (ESFRI) FX The authors would like to acknowledge economical support from the Spanish Ministry of Economy and Competitiveness through grants AIC-A-2011-0638, BIO2013-44647-R and BFU2013-41249-P; the Comunidad de Madrid through grant CAM (S2010/BMD-2305), NSF through Grant 1114901 and NRAMM through grant GM103310. C.O.S. Sorzano is recipient of a Ramon y Cajal fellowship. J. Vargas is recipient of a Juan de la Cierva fellowship with reference JCI-2011-10185. This work was partly funded by Instruct, part of the European Strategy Forum on Research Infrastructures (ESFRI) and supported by national member subscriptions. NR 9 TC 8 Z9 8 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 EI 1095-8657 J9 J STRUCT BIOL JI J. Struct. Biol. PD JUN PY 2015 VL 190 IS 3 BP 348 EP 359 DI 10.1016/j.jsb.2015.04.003 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CK3KS UT WOS:000356115600009 PM 25913484 ER PT J AU Wack, AN Holland, CJ Lopez, JE Schwan, TG Bronson, E AF Wack, Allison N. Holland, Cynthia J. Lopez, Job E. Schwan, Tom G. Bronson, Ellen TI SUSPECTED LYME BORRELIOSIS IN A CAPTIVE ADULT CHIMPANZEE (PAN TROGLODYTES) SO JOURNAL OF ZOO AND WILDLIFE MEDICINE LA English DT Article DE Borrelia burgdorferi; Borreliosis; Chimpanzee; Lyme disease; Pan troglodytes ID DISEASE; BURGDORFERI; PREVENTION; MODEL AB An 18-yr-old female captive-born chimpanzee (Pan troglodytes) presented with an intermittent history of inappetence, lethargy, and lower limb stiffness. No notable abnormalities were found on exam or complete blood cell count and serum biochemistry analysis. Serologic testing was strongly positive via indirect fluorescent antibody testing and Western blot for Borrelia burgdorferi. Treatment with doxycycline was initiated, and a clinical response was seen within 1 wk. Convalescent serum exhibited an eightfold increase in titer. Serologic testing was performed on several conspecifics with banked serum; while some low positive titers were present and presumed indicative of past exposure, no titer was elevated to the extent of the affected chimpanzee during its course of disease. To the authors' knowledge, this is the first report of suspected Lyme borreliosis in a great ape species, and the case originates from an area of the United States with a high incidence of human borreliosis. C1 [Wack, Allison N.; Bronson, Ellen] Maryland Zoo Baltimore, Baltimore, MD 21217 USA. [Holland, Cynthia J.] Protatek Reference Lab, Mesa, AZ 85210 USA. [Lopez, Job E.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Wack, AN (reprint author), Maryland Zoo Baltimore, 1876 Mansion House Dr, Baltimore, MD 21217 USA. EM allisonwack@gmail.com FU Division of Intramural Research, NIAID, NIH FX This work was partially supported by the Division of Intramural Research, NIAID, NIH. NR 10 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC ZOO VETERINARIANS PI YULEE PA 581705 WHITE OAK ROAD, YULEE, FL 32097 USA SN 1042-7260 EI 1937-2825 J9 J ZOO WILDLIFE MED JI J. Zoo Wildl. Med. PD JUN PY 2015 VL 46 IS 2 BP 423 EP 426 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA CK2DU UT WOS:000356021600044 PM 26056910 ER PT J AU Souza, ACP Yuen, PST Star, RA AF Souza, Ana Carolina P. Yuen, Peter S. T. Star, Robert A. TI Microparticles: markers and mediators of sepsis-induced microvascular dysfunction, immunosuppression, and AKI SO KIDNEY INTERNATIONAL LA English DT Review DE biomarkers; coagulopathy; endothelial dysfunction; phosphatidylserine; thrombosis; tissue factor ID ACUTE KIDNEY INJURY; ENDOTHELIAL PROGENITOR CELLS; NECROSIS-FACTOR-ALPHA; NEUTROPHIL-DERIVED MICROPARTICLES; CRITICALLY-ILL PATIENTS; BETA-COMMON RECEPTOR; INTENSIVE-CARE-UNIT; GROWTH-FACTOR; SEPTIC SHOCK; MICROCIRCULATORY DYSFUNCTION AB Sepsis is a severe and complex syndrome that lacks effective prevention or therapeutics. The effects of sepsis on the microvasculature have become an attractive area for possible new targets and therapeutics. Microparticles (MPs) are cell membrane-derived particles that can promote coagulation, inflammation, and angiogenesis, and they can participate in cell-to-cell communication. MPs retain cell membrane and cytoplasmic constituents of their parental cells, including two procoagulants: phosphatidylserine and tissue factor. We highlight the role of microparticles released by endothelial and circulating cells after sepsis-induced microvascular injury, and we discuss possible mechanisms by which microparticles can contribute to endothelial dysfunction, immunosuppression, and multiorgan dysfunction including sepsis-AKI. Once viewed as cellular byproducts, microparticles are emerging as a new class of markers and mediators in the pathogenesis of sepsis. C1 [Souza, Ana Carolina P.; Yuen, Peter S. T.; Star, Robert A.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RP Star, RA (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, 10 Ctr Dr,Bldg 10,3N108, Bethesda, MD 20892 USA. EM starr@niddk.nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) FX This research was supported by the Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). NR 101 TC 8 Z9 10 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2015 VL 87 IS 6 BP 1100 EP 1108 DI 10.1038/ki.2015.26 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CK1IL UT WOS:000355960900006 PM 25692956 ER PT J AU Seitz, AE Adjemian, J Steiner, CA Prevots, DR AF Seitz, Amy E. Adjemian, Jennifer Steiner, Claudia A. Prevots, D. Rebecca TI Spatial epidemiology of blastomycosis hospitalizations: detecting clusters and identifying environmental risk factors SO MEDICAL MYCOLOGY LA English DT Article DE epidemiology; blastomycosis; Blastomyces dermatitidis; Blastomyces gilchristii ID NORTH CENTRAL WISCONSIN; CANINE BLASTOMYCOSIS; NATURAL SITES; DERMATITIDIS; USA; OUTBREAK; SOIL; COCCIDIOIDOMYCOSIS; WATERWAYS; ILLINOIS AB Blastomycosis is a disease caused by endemic fungi that ranges from severe pulmonary or disseminated to mild or asymptomatic. Environmental factors associated with it are not well described throughout the endemic area. We used the intramural State Inpatient Database from the Agency for Healthcare Research and Quality and ArcMap GIS to identify geographic high-risk clusters of blastomycosis hospitalizations in 13 states in the US endemic regions (AR, IA, IL, IN, KY, LA, MI, MN, MO, MS, OH, TN, and WI). We then used logistic regression to identify risk factors associated with these high-risk clusters. We describe six clusters of counties in which there was an elevated incidence of blastomycosis hospitalizations. We identified maximum mean annual temperature, percentage of persons aged a parts per thousand yen65 years, and mercury and copper soil content as being associated with high-risk clusters. Specifically, the odds of a county being part of a high-risk cluster was associated with increasing percentage of population over age 65, decreasing maximum temperature, increasing mercury, and decreasing copper soil content. Healthcare providers should be aware of these high-risk areas so that blastomycosis can be included, as appropriate, in a differential diagnosis for patients currently or previously residing in these areas. C1 [Seitz, Amy E.; Adjemian, Jennifer; Prevots, D. Rebecca] NIAID, NIH, Epidemiol Unit, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Seitz, Amy E.] George Washington Univ, Dept Epidemiol & Biostat, Milken Inst Sch Publ Hlth, Washington, DC USA. [Steiner, Claudia A.] USA Healthcare Res & Qual, Healthcare Cost Utilizat Project, Rockville, MD USA. RP Seitz, AE (reprint author), 8 West Dr,MSC 2665, Bethesda, MD 20892 USA. EM seitza@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We would like to thank the state data organizations that contribute data to the Healthcare Cost and Utilization Project, without whom this study would not be possible. The authors would also like to thank Sean Cleary for his careful review and suggestions. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 45 TC 2 Z9 2 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1369-3786 EI 1460-2709 J9 MED MYCOL JI Med. Mycol. PD JUN PY 2015 VL 53 IS 5 BP 447 EP 454 DI 10.1093/mmy/myv014 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA CK5GA UT WOS:000356249800003 PM 25908653 ER PT J AU Hanaoka, H Nagaya, T Sato, K Nakamura, Y Watanabe, R Harada, T Gao, W Feng, MQ Phung, Y Kim, I Paik, CH Choyke, PL Ho, M Kobayashi, H AF Hanaoka, Hirofumi Nagaya, Tadanobu Sato, Kazuhide Nakamura, Yuko Watanabe, Rira Harada, Toshiko Gao, Wei Feng, Mingqian Phung, Yen Kim, Insook Paik, Chang H. Choyke, Peter L. Ho, Mitchell Kobayashi, Hisataka TI Glypican-3 Targeted Human Heavy Chain Antibody as a Drug Carrier for Hepatocellular Carcinoma Therapy SO MOLECULAR PHARMACEUTICS LA English DT Article DE heavy-chain antibody; intratumoral distribution; hepatoma; Glypican-3; photoimmunotherapy ID EXPRESSION; RETENTION; MARKER; CELLS AB Glypican-3 (GPC3) represents an attractive target for hepatocellular carcinoma (HCC) therapy because it is highly expressed in HCC but not in adult normal tissue. Recently, high affinity anti-GPC3 antibodies have been developed; however, full antibodies may not penetrate evenly into tumor parenchyma, reducing their effectiveness. In this study, we compared a Whole IgG antibody, anti-GPC3 YP7, with an anti-GPC3 human heavy chain antibody, HN3, with regard to their relative therapeutic effects. Both YP7 and HN3 bound to GPC3-positive A431/G1 cells and were internalized by the cells by in vitro evaluation with I-125- and In-111-radiolabeling antibodies. In vivo bio distribution and tumor accumulation was performed with In-111-labeled antibodies, and intratumoral Microdistribution was evaluated using fluorescently labeled antibodies (IR700)HN3 showed similar high Minor accumulation but superior homogeneity within the tumor compared with YP7. Using the same IR700 conjugated antibodies photoimmunotherapy (PIT) Was performed in vitro and in a tumor-bearing mouse model in vivo. PIT with IR700-HN3 and IR700-YP7 demonstrated that comparable results could be achieved despite of low reaccumulation 24 h after the first NIR light exposure. These results indicated that a heavy-chain antibody, HN3 showed More favorable Characteristics than YP7, a conventional IgG, as a therapeutic antibody platform for designing molecularly targeted agents against HCC. C1 [Hanaoka, Hirofumi; Nagaya, Tadanobu; Sato, Kazuhide; Nakamura, Yuko; Watanabe, Rira; Harada, Toshiko; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gao, Wei; Feng, Mingqian; Phung, Yen; Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kim, Insook] Leidos Biomed Res Inc, Appl Dev Res Directorate, Frederick Natl Lab, Frederick, MD 21702 USA. [Paik, Chang H.] NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Radiol & Imaging Sci,Warren Grant Magnuson Clin C, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. K.S. is supported with JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH. NR 23 TC 9 Z9 9 U1 0 U2 9 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 JUN PY 2015 VL 12 IS 6 BP 2151 EP 2157 DI 10.1021/acs.molpharmaceut.5b00132 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CJ6XG UT WOS:000355637900044 PM 25955255 ER PT J AU Naumova, AV Modo, M Moore, A Frank, JA Murry, CE AF Naumova, Anna V. Modo, Michel Moore, Anna Frank, Joseph A. Murry, Charles E. TI Cardiac regeneration validated Reply SO NATURE BIOTECHNOLOGY LA English DT Letter C1 [Naumova, Anna V.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Naumova, Anna V.; Murry, Charles E.] Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98195 USA. [Naumova, Anna V.; Murry, Charles E.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA. [Modo, Michel] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Modo, Michel] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA USA. [Modo, Michel] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Modo, Michel] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. [Moore, Anna] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Frank, Joseph A.] NIH, Radiol & Imaging Sci, Clin, Bethesda, MD 20892 USA. [Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Murry, Charles E.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Murry, Charles E.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Murry, Charles E.] Univ Washington, Dept Med Cardiol, Seattle, WA 98195 USA. RP Naumova, AV (reprint author), Univ Washington, Dept Radiol, Seattle, WA 98195 USA. EM murry@uw.edu NR 5 TC 1 Z9 1 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2015 VL 33 IS 6 BP 587 EP 587 DI 10.1038/nbt.3257 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CK2DE UT WOS:000356019700010 PM 26057970 ER PT J AU Brown, DC Agnello, K Ladarola, MJ AF Brown, Dorothy C. Agnello, Kimberly Ladarola, Michael J. TI Intrathecal resiniferatoxin in a dog model: efficacy in bone cancer pain SO PAIN LA English DT Article DE Bone cancer; Canine model; Resiniferatoxin; TRPV1; Deafferentation ID SUBSTANCE P-SAPORIN; ANIMAL-MODELS; UNILATERAL DEAFFERENTATION; CAPSAICIN-RECEPTOR; OSTEOARTHRITIS; INVENTORY; NEURONS; DISEASE; TUMORS; HEAT AB Resiniferatoxin (RTX) is the most potent among all known endogenous and synthetic agonists for the transient receptor potential vanilloid 1 (TRPV1) receptor, which is a calcium-permeable nonselective cation channel, expressed on the peripheral and central terminals of small-diameter sensory neurons. Prolonged calcium influx induced by FIX causes cytotoxicity and death of only those sensory neurons that express the TRPV1 ion channel leading to selective targeting and permanent deletion of the TRPV1 expressing C-fiber neuronal cell bodies in the dorsal root ganglia. The goal of this project was to provide preclinical efficacy data, that intrathecal RTX could provide effective pain relief and improve function in dogs with bone cancer without significant long-term side effects. In a single-blind, controlled study, 72 companion dogs with bone cancer pain were randomized to standard of care analgesic therapy alone (control, n = 36) or 1.2 mu g/kg intrathecal RTX in addition to standard of care analgesic therapy (treated, n = 36). Significantly more dogs in the control group (78%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization, than dogs that were treated with RTX (50%; P < 0.03); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with RTX (P < 0.02). The analgesic effect was documented in these dogs without any evidence of development of deafferentation pain syndrome that can be seen with neurolytic therapies. C1 [Brown, Dorothy C.; Agnello, Kimberly] Univ Penn, Sch Vet Med, Dept Clin Studies, Philadelphia, PA 19104 USA. [Ladarola, Michael J.] NIH, Ctr Clin, Dept Perioperat Med, Anesthesia Sect, Bethesda, MD 20892 USA. RP Brown, DC (reprint author), Univ Penn, Philadelphia Sch Vet Med, Dept Clin Studies, 3900 Delancey St, Philadelphia, PA 19104 USA. EM dottie@vet.upenn.edu FU National Institutes of Health, Bethesda, MD [5K08DA017720] FX This study was funded by a grant from the National Institutes of Health (5K08DA017720), Bethesda, MD. On March 22, 2014, D. C. Brown began acting as a consultant for Sorrento Therapeutics, which is developing RTX for human and veterinary applications, as a key opinion leader with the FDA assisting in study design and data interpretation. NR 39 TC 6 Z9 6 U1 1 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 JUN PY 2015 VL 156 IS 6 BP 1018 EP 1024 DI 10.1097/j.pain.0000000000000115 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CJ6ZE UT WOS:000355642900008 PM 25659068 ER PT J AU Swartout, KM Parrott, DJ Cohn, AM Hagman, BT Gallagher, KE AF Swartout, Kevin M. Parrott, Dominic J. Cohn, Amy M. Hagman, Brett T. Gallagher, Kathryn E. TI Development of the Abbreviated Masculine Gender Role Stress Scale SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE masculine gender role stress; psychometrics; classical test theory; item response theory ID ITEM RESPONSE THEORY; MALE-ROLE NORMS; ALCOHOLISM SCREENING-TEST; GAY MEN; TRAIT ANGER; BRIEF-MAST; SEXUAL MINORITIES; COLLEGE-STUDENTS; PROBLEM INDEX; AGGRESSION AB Data gathered from 6 independent samples (n = 1,729) that assessed men's masculine gender role stress in college and community males were aggregated used to determine the reliability and validity of an abbreviated version of the Masculine Gender Role Stress (MGRS) Scale. The 15 items with the highest item-to-total scale correlations were used to create an abbreviated MGRS Scale. Psychometric properties of each of the 15 items were examined with item response theory (IRT) analysis, using the discrimination and threshold parameters. IRT results showed that the abbreviated scale may hold promise at capturing the same amount of information as the full 40-item scale. Relative to the 40-item scale, the total score of the abbreviated MGRS Scale demonstrated comparable convergent validity using the measurement domains of masculine identity, hypermasculinity, trait anger, anger expression, and alcohol involvement. An abbreviated MGRS Scale may be recommended for use in clinical practice and research settings to reduce cost, time, and patient/participant burden. Additionally, IRT analyses identified items with higher discrimination and threshold parameters that may be used to screen for problematic gender role stress in men who may be seen in routine clinical or medical practice. C1 [Swartout, Kevin M.; Parrott, Dominic J.; Gallagher, Kathryn E.] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. [Cohn, Amy M.] Univ S Florida, Dept Mental Hlth Law & Policy, Tampa, FL 33620 USA. [Hagman, Brett T.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD USA. RP Swartout, KM (reprint author), Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. EM kswartout@gsu.edu FU National Institute on Alcohol Abuse and Alcoholism Grant [R01 AA015445] FX The research design and data collection were supported by National Institute on Alcohol Abuse and Alcoholism Grant R01 AA015445 awarded to Dominic J. Parrott. NR 72 TC 0 Z9 0 U1 4 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD JUN PY 2015 VL 27 IS 2 BP 489 EP 500 DI 10.1037/a0038443 PG 12 WC Psychology, Clinical SC Psychology GA CK1AY UT WOS:000355939000013 PM 25528163 ER PT J AU Choyke, PL AF Choyke, Peter L. TI Science to Practice: Monitoring Oncolytic Virus Therapy with Chemical Exchange Saturation Transfer MR Imaging-Wishful Thinking? SO RADIOLOGY LA English DT Article AB Farrar et al (1) demonstrate that modifying an oncolytic virus (OV) so that it produces excess protein when it infects a cancer cell is a process that can be detected both in vitro and in vivo in infected cancer cells by using chemical exchange saturation transfer (CEST) magnetic resonance (MR) imaging. The effect is at the limits of MR imaging detection (approximately 1%), but experience with functional MR imaging of the brain, with comparably small effects, should give pause to anyone who immediately writes this observation off as an exercise in wishful thinking. OVs are improving in their specificity, virulence, and ability to induce immune responses. Now, they have been modified to express proteins that are detectable with CEST MR imaging early after delivery into a tumor. This is clearly a surprising and hopeful development in the long road of OVs from the laboratory to the clinic. C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B69F, Bethesda, MD 20892 USA. EM pchoyke@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2015 VL 275 IS 3 BP 625 EP 626 DI 10.1148/radiol.2015150537 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1SZ UT WOS:000355988900001 PM 25997128 ER PT J AU de Gonzalez, AB Kleinerman, RA AF de Gonzalez, Amy Berrington Kleinerman, Ruth A. TI CT Scanning: Is the Contrast Material Enhancing the Radiation Dose and Cancer Risk as Well as the Image? SO RADIOLOGY LA English DT Editorial Material ID DOUBLE-STRAND BREAKS; COMPUTED-TOMOGRAPHY; IONIZING-RADIATION; GAMMA-H2AX; LYMPHOCYTES; CHILDHOOD; COHORT; AGENTS; SCANS C1 [de Gonzalez, Amy Berrington; Kleinerman, Ruth A.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP de Gonzalez, AB (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM berringtona@mail.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478 NR 23 TC 4 Z9 4 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2015 VL 275 IS 3 BP 627 EP 629 DI 10.1148/radiol.2015150605 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CK1SZ UT WOS:000355988900002 ER PT J AU Bolnick, JM Kilburn, BA Bolnick, AD Diamond, MP Singh, M Hertz, M Dai, J Armant, DR AF Bolnick, Jay M. Kilburn, Brian A. Bolnick, Alan D. Diamond, Michael P. Singh, Manvinder Hertz, Michael Dai, Jing Armant, D. Randall TI Sildenafil Prevents Apoptosis of Human First-Trimester Trophoblast Cells Exposed to Oxidative Stress: Possible Role for Nitric Oxide Activation of 3,5-cyclic Guanosine Monophosphate Signaling SO REPRODUCTIVE SCIENCES LA English DT Article DE sildenafil; apoptosis; nitric oxide; cGMP ID ENDOTHELIAL GROWTH-FACTOR; ISCHEMIA-REPERFUSION INJURY; MENSTRUAL-CYCLE; EARLY-PREGNANCY; ANTIANGIOGENIC FACTORS; DEPENDENT RELAXATION; RESISTANCE ARTERIES; HUMAN ENDOMETRIUM; HUMAN PLACENTA; IN-VITRO AB Human first-trimester trophoblast cells proliferate at low O-2, but survival is compromised by oxidative stress, leading to uteroplacental insufficiency. The vasoactive drug, sildenafil citrate (Viagra, Sigma, St Louis, Missouri), has proven useful in reducing adverse pregnancy outcomes. An important biological function of this pharmaceutical is its action as an inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterase type 5 activity, which suggests that it could have beneficial effects on trophoblast survival. To investigate whether sildenafil can prevent trophoblast cell death, human first-trimester villous explants and the HTR-8/SVneo cytotrophoblast cell line were exposed to hypoxia and reoxygenation (H/R) to generate oxidative stress, which induces apoptosis. Apoptosis was optimally inhibited during H/R by 350 ng/mL sildenafil. Sildenafil-mediated survival was reversed by l-N-G-nitro-l-arginine methyl ester hydrochloride or cGMP antagonist, indicating a dependence on both nitric oxide (NO) and cGMP. Indeed, either a cGMP agonist or an NO generator was cytoprotective independent of sildenafil. These findings suggest a novel intervention route for patients with recurrent pregnancy loss or obstetrical placental disorders. C1 [Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan D.; Singh, Manvinder; Hertz, Michael; Dai, Jing; Armant, D. Randall] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Diamond, Michael P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA USA. [Armant, D. Randall] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. [Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA. RP Armant, DR (reprint author), Wayne State Univ, Mott Ctr Human Growth & Dev, 275 E Hancock St, Detroit, MI 48201 USA. EM D.Armant@Wayne.edu OI Diamond, Michael/0000-0001-6353-4489; Armant, D. Randall/0000-0001-5904-9325 FU Intramural Research Program of the National Institute for Child Health and Human Development, National Institutes of Health; NIH [HD071408]; W.K. Kellogg Foundation FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Supported in part by the Intramural Research Program of the National Institute for Child Health and Human Development, National Institutes of Health and grants from the NIH (HD071408) and the W.K. Kellogg Foundation. NR 51 TC 1 Z9 1 U1 0 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD JUN PY 2015 VL 22 IS 6 BP 718 EP 724 DI 10.1177/1933719114557894 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CK2AR UT WOS:000356012200011 PM 25431453 ER PT J AU Biek, R Pybus, OG Lloyd-Smith, JO Didelot, X AF Biek, Roman Pybus, Oliver G. Lloyd-Smith, James O. Didelot, Xavier TI Measurably evolving pathogens in the genomic era SO TRENDS IN ECOLOGY & EVOLUTION LA English DT Article DE bacteria; DNA virus; epidemiological models; evolutionary rate; infectious disease; phylodynamics ID MYCOBACTERIUM-TUBERCULOSIS; INFECTIOUS-DISEASE; CLOSTRIDIUM-DIFFICILE; POPULATION GENOMICS; TRANSMISSION TREES; EVOLUTIONARY RATES; BACTERIAL GENOMES; ESCHERICHIA-COLI; MOLECULAR CLOCKS; YERSINIA-PESTIS AB Current sequencing technologies have created unprecedented opportunities for studying microbial populations. For pathogens with comparatively low per-site mutation rates, such as DNA viruses and bacteria, whole-genome sequencing can reveal the accumulation of novel genetic variation between population samples taken at different times. The concept of 'measurably evolving populations' and related analytical approaches have provided powerful insights for fast-evolving RNA viruses, but their application to other pathogens is still in its infancy. We argue that previous distinctions between slow- and fast-evolving pathogens become blurred once evolution is assessed at a genome-wide scale, and we highlight important analytical challenges to be overcome to infer pathogen population dynamics from genomic data. C1 [Biek, Roman] Univ Glasgow, Boyd Orr Ctr Populat & Ecosyst Hlth, Inst Biodivers Anim Hlth & Comparat Med, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. [Biek, Roman; Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford, England. [Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [Didelot, Xavier] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London, England. RP Biek, R (reprint author), Univ Glasgow, Boyd Orr Ctr Populat & Ecosyst Hlth, Inst Biodivers Anim Hlth & Comparat Med, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. EM roman.biek@glasgow.ac.uk RI Lloyd-Smith, James/K-4080-2012; OI Lloyd-Smith, James/0000-0001-7941-502X; Didelot, Xavier/0000-0003-1885-500X; Biek, Roman/0000-0003-3471-5357; Pybus, Oliver/0000-0002-8797-2667 FU RAPIDD program of the Science and Technology Directorate of the US Department of Homeland Security; National Institutes of Health (NIH) Fogarty International Center; NIH [RO1 AI047498]; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/L010569/1]; NSF [EF-0928690, OCE-1335657]; European Research Council under the European Commission [614725-PATHPHYLODYN]; National Institute for Health Research (NIHR) Health Protection Research Unit FX This paper benefited from the discussions during a workshop at the University of Glasgow in 2013, funded by the RAPIDD program of the Science and Technology Directorate of the US Department of Homeland Security and National Institutes of Health (NIH) Fogarty International Center. We would like to thank the workshop participants for the contributions made during the workshop. We also thank Allen Rodrigo and one anonymous reviewer for their constructive comments on an earlier version of this paper. R.B. is supported by NIH grant RO1 AI047498 and Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/L010569/1. J.L-S. is funded by NSF grants EF-0928690 and OCE-1335657. O.G.P. received funding from the European Research Council under the European Commission Seventh Framework Programme (FP7/2007-2013)/European Research Council grant agreement 614725-PATHPHYLODYN. X.D. would like to acknowledge National Institute for Health Research (NIHR) Health Protection Research Unit funding. NR 83 TC 27 Z9 27 U1 7 U2 45 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0169-5347 J9 TRENDS ECOL EVOL JI Trends Ecol. Evol. PD JUN PY 2015 VL 30 IS 6 BP 306 EP 313 DI 10.1016/j.tree.2015.03.009 PG 8 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA CK4JO UT WOS:000356190300007 PM 25887947 ER PT J AU Hernandez-Andrade, E AF Hernandez-Andrade, E. TI Re: Assessment by three-dimensional power Doppler ultrasound of cerebral blood flow perfusion in fetuses with congenital heart disease. S. Zeng, J. Zhou, Q. Peng, L. Tian, G. Xu, Y. Zhao, T. Wang and Q. Zhou. Ultrasound Obstet Gynecol 2015; 45: 649-656 SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Editorial Material C1 Wayne State Univ, Sch Med, Perinatol Res Branch, NICHD,NIH,DHHS,Dept Obstet & Gynecol,Div Maternal, Detroit, MI 48202 USA. RP Hernandez-Andrade, E (reprint author), Wayne State Univ, Sch Med, Perinatol Res Branch, NICHD,NIH,DHHS,Dept Obstet & Gynecol,Div Maternal, Detroit, MI 48202 USA. EM ehernand@med.wayne.edu 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 0960-7692 EI 1469-0705 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD JUN PY 2015 VL 45 IS 6 BP 629 EP 629 DI 10.1002/uog.14887 PG 1 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA CJ7KU UT WOS:000355674700002 PM 26032709 ER PT J AU Insel, TR AF Insel, Thomas R. TI The NIMH experimental medicine initiative SO WORLD PSYCHIATRY LA English DT Editorial Material ID TRIALS C1 NIMH, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 9 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD JUN PY 2015 VL 14 IS 2 BP 151 EP 153 DI 10.1002/wps.20227 PG 3 WC Psychiatry SC Psychiatry GA CK2BZ UT WOS:000356015600005 PM 26043323 ER PT J AU Cenderello, G Tittle, V Pasa, A Dentone, C Artioli, S Setti, M Giacomini, M Fraccaro, P Viscoli, C Cassola, G Di Biagio, A Barbour, A Nelson, M AF Cenderello, Giovanni Tittle, Victoria Pasa, Ambra Dentone, Chiara Artioli, Stefania Setti, Maurizio Giacomini, Mauro Fraccaro, Paolo Viscoli, Claudio Cassola, Giovanni Di Biagio, Antonio Barbour, Alison Nelson, Mark TI Inpatient admissions of patients living with HIV in two European centres (UK and Italy); comparisons and contrasts SO JOURNAL OF INFECTION LA English DT Letter ID COINFECTION; POPULATION; RATES; AIDS C1 [Cenderello, Giovanni; Cassola, Giovanni] EO Osped Galliera, Malattie Infett, I-16128 Genoa, Italy. [Tittle, Victoria; Barbour, Alison; Nelson, Mark] Chelsea & Westminster Hosp, HIV Unit, London, England. [Pasa, Ambra] EO Osped Galliera, Informat Technol, I-16128 Genoa, Italy. [Dentone, Chiara] ASL1, Malattie Infett, Imperia, Italy. [Artioli, Stefania] ASL5, Malattie Infett, La Spezia, Italy. [Setti, Maurizio] Natl Canc Inst, Clin Orientamento Immunol, IRCCS AOU San Martino IST, Genoa, Italy. [Giacomini, Mauro; Fraccaro, Paolo] Univ Genoa, Dept Informat Bioengn Robot & Syst Engn, Ctr Excellence Biomed Res, Genoa, Italy. [Giacomini, Mauro; Fraccaro, Paolo] Univ Manchester, NIHR Greater Manchester Primary Care Patient Safet, Manchester M13 9PL, Lancs, England. [Giacomini, Mauro; Fraccaro, Paolo] Univ Manchester, Hlth eRes Ctr, Manchester M13 9PL, Lancs, England. [Viscoli, Claudio; Di Biagio, Antonio] Natl Canc Inst, Clin Malattie Infett, IRCCS AOU San Martino IST, Genoa, Italy. RP Cenderello, G (reprint author), EO Osped Galliera, Malattie Infett, Via Volta 8, I-16128 Genoa, Italy. EM giovanni.cenderello@galliera.it OI Giacomini, Mauro/0000-0001-5646-2034; Fraccaro, Paolo/0000-0002-5213-7071; Di Biagio, Antonio/0000-0003-1436-5089 NR 12 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD JUN PY 2015 VL 70 IS 6 BP 690 EP 694 DI 10.1016/j.jinf.2014.12.009 PG 6 WC Infectious Diseases SC Infectious Diseases GA CH5ZT UT WOS:000354115600022 PM 25572999 ER PT J AU Piper, MR Freedman, DM Robien, K Kopp, W Rager, H Horst, RL Stolzenberg-Solomon, RZ AF Piper, Marina R. Freedman, D. Michal Robien, Kim Kopp, William Rager, Helen Horst, Ronald L. Stolzenberg-Solomon, Rachael Z. TI Vitamin D-binding protein and pancreatic cancer: a nested case-control study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE 25-hydroxyvitamin D; nested case-control; pancreatic cancer; vitamin D-binding protein; prediagnostic status; prospective study ID GENOME-WIDE ASSOCIATION; 25-HYDROXYVITAMIN D; SCREENING TRIAL; BLADDER-CANCER; CELL NUMBER; D-RECEPTOR; D ANALOGS; IN-VITRO; RISK; PROSTATE AB Background: Vitamin D binding protein (DBP) is the primary carrier of 25-hydroxyvitamin D [25(OH)D] in the circulation. One prospective study in male smokers found a protective association between DBP and pancreatic cancer, particularly among men with higher 25(OH)D concentrations. Objective: The objective was to examine the association between DBP and pancreatic cancer risk in an American population. Design: We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial cohort of men and women aged 55-74 y at baseline. Between 1993 and 2010, 295 incident pancreatic adenocarcinoma cases were reported (follow-up to 15.1 y). Two controls (n = 590) were matched to each case by age, race, sex, and month of blood draw. We calculated smoking- and diabetes-adjusted ORs and 95% CIs with the use of conditional logistic regression. Results: DBP concentration was not significantly associated with pancreatic cancer overall [highest (>= 7149.4 nmol/L) vs. lowest (<3670.4 nmol/L) quintile; OR: 1.75; 95% CI: 0.91, 3.37; P-trend = 0.25]. For serum 25(OH)D compared with the referent (50 to <75 nmol/L), individuals in the highest group had a significantly higher risk (>= 100 nmol/L; OR: 3.23; 95% CI: 1.24, 8.44), whereas those in the lowest group had no significant association (<25 nmol/L; OR: 2.50; 95% CI: 0.92, 6.81). Further adjustment for DBP did not alter this association. Conclusion: Our results do not support the hypothesis that serum DBP or 25(OH)D plays a protective role in pancreatic cancer. This trial was registered at clinicaltrials.gov as NCT00339495. C1 [Piper, Marina R.; Stolzenberg-Solomon, Rachael Z.] Natl Canc Inst, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Freedman, D. Michal] Natl Canc Inst, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Rockville, MD 20850 USA. [Robien, Kim] George Washington Univ, Dept Epidemiol & Biostat, Milken Inst, Sch Publ Hlth, Washington, DC USA. [Robien, Kim] George Washington Univ, Dept Exercise Sci, Milken Inst, Sch Publ Hlth, Washington, DC USA. [Kopp, William; Rager, Helen] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Clin Support Lab, Frederick, MD USA. [Horst, Ronald L.] Iowa State Univ, Heartland Assays Inc, Ames, IA USA. RP Stolzenberg-Solomon, RZ (reprint author), Natl Canc Inst, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E420, Rockville, MD 20850 USA. EM rs221z@nih.gov OI Robien, Kim/0000-0002-2120-2280 FU Intramural Research Program of the NIH, Division of Cancer Epidemiology and Genetics, National Cancer Institute; [HHSN261200800001E] FX Supported by the Intramural Research Program of the NIH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, and under contract no. HHSN261200800001E. NR 35 TC 3 Z9 3 U1 0 U2 4 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2015 VL 101 IS 6 BP 1206 EP 1215 DI 10.3945/ajcn.114.096016 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CJ6YU UT WOS:000355641900014 PM 25904602 ER PT J AU Reis, JP Michos, ED Selvin, E Pankow, JS Lutsey, PL AF Reis, Jared P. Michos, Erin D. Selvin, Elizabeth Pankow, James S. Lutsey, Pamela L. TI Race, vitamin D-binding protein gene polymorphisms, 25-hydroxyvitamin D, and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diabetes; race; vitamin D binding protein polymorphisms; cohort study ID NUTRITION EXAMINATION SURVEY; IMPAIRED GLUCOSE-TOLERANCE; BONE-MINERAL DENSITY; 3RD NATIONAL-HEALTH; D-ENDOCRINE SYSTEM; D DEFICIENCY; SERUM 25-HYDROXYVITAMIN-D; MENDELIAN RANDOMIZATION; RACIAL-DIFFERENCES; AFRICAN-AMERICANS AB Background: Low 25-hydroxyvitamin D [25(OH)D] is associated with diabetes, but few studies have examined racially diverse populations while also accounting for key vitamin D binding protein (DBP) gene polymorphisms. Objective: We sought to evaluate whether the association between 25(OH)D and incident diabetes varied by race and important DBP single nucleotide polymorphisms (SNPs). Design: We studied 10,222 adults (8120 whites, 2102 blacks) aged 46-70 y at baseline (1990-1992) from the ARIC (Atherosclerosis Risk in Communities) Study with follow-up for incident diabetes ascertained during study visits conducted in 1993-1995 and 1996 1998. Adjusted BRs and their 95% CIs for diabetes were estimated according to 25(OH)D status. Results: During follow-up there were 750 incident cases of diabetes. The association of 25(OH)D with diabetes varied by race (P-interaction = 0.004). Among whites, the adjusted HR for diabetes corresponding to each additional SD higher 25(OH)D concentration (21.3 nmol/L) was 0.95 (95% CI: 0.91, 0.99). No significant association was observed among blacks (HR: 1.06; 95% CI: 0.99, 1.14). There was evidence that the A allele at rs4588 and the Tallele at rs7041, which are reported to be associated with high and low DBP concentrations, respectively, modified the association between 25(OH)D and diabetes among whites (P-interaction < 0.05 for both) but not blacks (P-interaction > 0.50 for both). Conclusions: In this large, community-based study, low 25(OH)D concentrations were associated with diabetes among whites but not blacks. Interactions by key DBP SNPs varied between genotypes associated with either high or low DBP concentrations among whites but not blacks. Nevertheless, the findings from this prospective study suggest that there are important differences in the association of 25(OH)D with incident diabetes between white and black adults. C1 [Reis, Jared P.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Michos, Erin D.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. [Selvin, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Pankow, James S.; Lutsey, Pamela L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Reis, JP (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Suite 10186, Bethesda, MD 20892 USA. EM reisjp@mail.nih.gov FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; NHLBI [R01 HL103706]; National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK089174]; NIMBI CARe (Candidate Gene Resource) [N01-HC-65226] FX The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C. Further support was obtained by grant R01 HL103706 from the NHLBI with a supplement from the NIH Office of Dietary Supplements (to PLL) as well as the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK089174 to ES). Genotyping was supported through the NIMBI CARe (Candidate Gene Resource) contract N01-HC-65226. NR 46 TC 11 Z9 12 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2015 VL 101 IS 6 BP 1232 EP 1240 DI 10.3945/ajcn.115.107334 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CJ6YU UT WOS:000355641900017 PM 25926504 ER PT J AU Mueller, M Purnell, TS Mensah, GA Cooper, LA AF Mueller, Michael Purnell, Tanjala S. Mensah, George A. Cooper, Lisa A. TI Reducing Racial and Ethnic Disparities in Hypertension Prevention and Control: What Will It Take to Translate Research into Practice and Policy? SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; disparities; hypertension; interventions; prevention; policy; racial inequities; research translation ID BLOOD-PRESSURE CONTROL; RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR HEALTH DISPARITIES; PATIENT-PHYSICIAN COMMUNICATION; DISEASE MANAGEMENT PROGRAM; LIFE-STYLE INTERVENTION; PRIMARY-CARE PATIENTS; PAY-FOR-PERFORMANCE; AFRICAN-AMERICANS; MEDICATION ADHERENCE AB INTRODUCTION Despite available, effective therapies, racial and ethnic disparities in care and outcomes of hypertension persist. Several interventions have been tested to reduce disparities; however, their translation into practice and policy is hampered by knowledge gaps and limited collaboration among stakeholders. METHODS We characterized factors influencing disparities in blood pressure (BP) control by levels of an ecological model. We then conducted a literature search using PubMed, Scopus, and CINAHL databases to identify interventions targeted toward reducing disparities in BP control, categorized them by the levels of the model at which they were primarily targeted, and summarized the evidence regarding their effectiveness. RESULTS We identified 39 interventions and several state and national policy initiatives targeted toward reducing racial and ethnic disparities in BP control, 5 of which are ongoing. Most had patient populations that were majority African-American. Of completed interventions, 27 demonstrated some improvement in BP control or related process measures, and 7 did not; of the 6 studies examining disparities, 3 reduced, 2 increased, and 1 had no effect on disparities. CONCLUSIONS Several effective interventions exist to improve BP in racial and ethnic minorities; however, evidence that they reduce disparities is limited, and many groups are understudied. To strengthen the evidence and translate it into practice and policy, we recommend rigorous evaluation of pragmatic, sustainable, multilevel interventions; institutional support for training implementation researchers and creating broad partnerships among payers, patients, providers, researchers, policymakers, and community-based organizations; and balance and alignment in the priorities and incentives of each stakeholder group. C1 [Mueller, Michael; Cooper, Lisa A.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD 21218 USA. [Purnell, Tanjala S.] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. [Purnell, Tanjala S.; Cooper, Lisa A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Purnell, Tanjala S.; Cooper, Lisa A.] Johns Hopkins Ctr Eliminate Cardiovascular Hlth D, Baltimore, MD USA. [Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, Bethesda, MD 20892 USA. [Cooper, Lisa A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Cooper, Lisa A.] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. RP Cooper, LA (reprint author), Johns Hopkins Sch Med, Dept Med, Baltimore, MD 21218 USA. EM lisa.cooper@jhmi.edu FU Health Resources and Services Administration [HRSA-11-156]; National Heart, Lung and Blood Institute of the National Institutes of Health (NHLBI) [5T32HL007180]; NHLBI [K24 HL083113, P50 HL0105187] FX Dr Mueller is supported by Health Resources and Services Administration (HRSA-11-156). Dr Purnell was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health (NHLBI, 5T32HL007180). Dr Cooper is supported by NHLBI (K24 HL083113, P50 HL0105187). NR 91 TC 12 Z9 12 U1 3 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUN PY 2015 VL 28 IS 6 BP 699 EP 716 DI 10.1093/ajh/hpu233 PG 18 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CJ6ST UT WOS:000355624600001 PM 25498998 ER PT J AU Liu, FC He, J Gu, DF Rao, DC Huang, JF Hixson, JE Jaquish, CE Chen, JC Li, CW Yang, XL Li, JX Rice, TK Shimmin, LC Kelly, TN AF Liu, Fangchao He, Jiang Gu, Dongfeng Rao, Dabeeru C. Huang, Jianfeng Hixson, James E. Jaquish, Cashell E. Chen, Jichun Li, Changwei Yang, Xueli Li, Jianxin Rice, Treva K. Shimmin, Lawrence C. Kelly, Tanika N. TI Associations of Endothelial System Genes With Blood Pressure Changes and Hypertension Incidence: The GenSalt Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure changes; common variants; endothelial; hypertension ID SINGLE NUCLEOTIDE POLYMORPHISM; E-SELECTIN GENE; NITRIC-OXIDE; SYNTHASE GENE; GLOBAL BURDEN; NO SYNTHASE; DISEASE; SUSCEPTIBILITY; RELAXATION; VARIANTS AB BACKGROUD We used single-marker and novel gene-based methods to examine the associations of endothelial system genes with blood pressure (BP) changes and hypertension in a longitudinal family study. METHODS The Genetic Epidemiology Network of Salt Sensitivity follow-up study was conducted among 1,768 Chinese participants from 633 families. Nine BP measurements were obtained at baseline and at 2 follow-up visits using a random-zero sphygmomanometer. Mixed-effect models were used to assess the additive associations of 206 single-nucleotide polymorphisms (SNPs) in 15 endothelial system genes with longitudinal BP changes and hypertension incidence. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses. RESULTS Among those free from hypertension at baseline, 512 (32.1%) developed hypertension during the average 7.2 years of follow-up. In single-marker analyses, each copy of the minor alleles of correlated SELE markers rs4656704, rs6427212, and rs5368 were associated with increased risk of developing hypertension (Pfor trend = 1.48 x 10(-4), 6.69 x 10(-5), and 7.64 x 10(-5), respectively). In addition, the minor allele of SELE marker rs3917436 was associated with smaller diastolic BP (DBP) increases over time. Results of gene-based analyses confirmed associations of the SELE gene with the longitudinal BP phenotypes (P values < 1.00 x 10(-6) for DBP change and hypertension incidence). Furthermore, the DDAH1 and COL18A1 genes were associated with systolic BP change (P < 1.00 x 10(-6) and P = 4.00 x 10(-6), respectively), while EDNRA was associated with hypertension incidence (P = 2.39 x 10(-4)). CONCLUSIONS The current study provides strong evidence of a role of endothelial system genes in BP progression and hypertension incidence. C1 [Liu, Fangchao; Gu, Dongfeng; Huang, Jianfeng; Chen, Jichun; Yang, Xueli; Li, Jianxin] Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Dept Evidence Based Med, Fuwai Hosp,Natl Ctr Cardiovasc Dis, Beijing 100730, Peoples R China. [Liu, Fangchao; Gu, Dongfeng; Huang, Jianfeng; Chen, Jichun; Yang, Xueli; Li, Jianxin] Peking Union Med Coll, Beijing 100021, Peoples R China. [Liu, Fangchao; He, Jiang; Li, Changwei; Kelly, Tanika N.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Rao, Dabeeru C.; Rice, Treva K.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Hixson, James E.; Shimmin, Lawrence C.] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Jaquish, Cashell E.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. RP Kelly, TN (reprint author), Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Dept Evidence Based Med, Fuwai Hosp,Natl Ctr Cardiovasc Dis, Beijing 100730, Peoples R China. EM tkelly@tulane.edu RI Li, Changwei/S-5615-2016 OI Li, Changwei/0000-0002-9203-304X FU National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD [U01HL072507, R01HL087263, R01HL090682]; National Institutes of Health John E Fogarty International Center, Bethesda, MD [D43TW009107] FX This work was supported by a cooperative agreement project grant (U01HL072507, R01HL087263, and R01HL090682) from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD. F.L. was supported by a research training grant (D43TW009107) from National Institutes of Health John E Fogarty International Center, Bethesda, MD. NR 38 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUN PY 2015 VL 28 IS 6 BP 780 EP 788 DI 10.1093/ajh/hpu223 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CJ6ST UT WOS:000355624600010 PM 25424718 ER PT J AU Musser, JM Deleo, FR AF Musser, James M. DeLeo, Frank R. TI Molecular Pathogenesis Lessons from the World of Infectious Diseases Research SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID VIRUSES C1 [Musser, James M.] Houston Methodist Res Inst, Ctr Mol & Translat Human Infect Dis Res, Dept Pathol & Genom Med, Houston, TX USA. [Musser, James M.] Houston Methodist Hosp, Houston, TX 77401 USA. [DeLeo, Frank R.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Musser, JM (reprint author), Houston Methodist Hosp, Dept Pathol & Genom Med, 6565 Fannin St,Ste B490, Houston, TX 77401 USA. EM jmmusser@houstonmethodist.org OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS NR 13 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2015 VL 185 IS 6 BP 1502 EP 1504 DI 10.1016/j.ajpath.2015.03.004 PG 3 WC Pathology SC Pathology GA CJ2YL UT WOS:000355350500001 PM 25906759 ER PT J AU Kobayashi, SD Malachowa, N DeLeo, FR AF Kobayashi, Scott D. Malachowa, Natalia DeLeo, Frank R. TI Pathogenesis of Staphylococcus aureus Abscesses SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID SOFT-TISSUE INFECTIONS; PANTON-VALENTINE LEUKOCIDIN; FACTOR-BINDING-PROTEIN; ALPHA-TOXIN; UNITED-STATES; VIRULENCE DETERMINANTS; NEUTROPHIL RECRUITMENT; PASSIVE-IMMUNIZATION; EMERGENCY-DEPARTMENT; NASAL COLONIZATION AB Staphylococcus aureus causes many types of human infections and syndromes most notably skin and soft tissue infections. Abscesses are a frequent manifestation of S. aureus skin and soft tissue infections and are formed, in part, to contain the nidus of infection. Polymorphonuclear leukocytes (neutrophils) are the primary cellular host defense against S. aureus infections and a major component of S. aureus abscesses. These host cells contain and produce many antimicrobial agents that are effective at killing bacteria, but can also cause non-specific damage to host tissues and contribute to the formation of abscesses. By comparison, S. aureus produces several molecules that also contribute to the formation of abscesses. Such molecules include those that recruit neutrophils, cause host cell lysis, and are involved in the formation of the fibrin capsule surrounding the abscess. Herein, we review our current knowledge of the mechanisms and processes underlying the formation of S. aureus abscesses, including the involvement of polymorphonuclear Leukocytes, and provide a brief overview of therapeutic approaches. C1 [Kobayashi, Scott D.; Malachowa, Natalia; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Deleo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S Fourth St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU National Institute of Allergy and Infectious Diseases, NIH, Intramural Research Program FX Supported by the National Institute of Allergy and Infectious Diseases, NIH, Intramural Research Program (S.D.K., N.M., and F.R.D.). NR 103 TC 12 Z9 12 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2015 VL 185 IS 6 BP 1518 EP 1527 DI 10.1016/j.ajpath.2014.11.030 PG 10 WC Pathology SC Pathology GA CJ2YL UT WOS:000355350500003 PM 25749135 ER PT J AU Kash, JC Taubenberger, JK AF Kash, John C. Taubenberger, Jeffery K. TI The Role of Viral, Host, and Secondary Bacterial Factors in Influenza Pathogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID A VIRUS PB1-F2; PANDEMIC INFLUENZA; NADPH OXIDASE; RAPID SELECTION; INFECTION; PROTEIN; HEMAGGLUTININ; PATHOGENICITY; PNEUMONIA; MORTALITY AB Influenza A virus infections in humans generally cause self-limited infections, but can result in severe disease, secondary bacterial pneumonias, and death. Influenza viruses can replicate in epithelial cells throughout the respiratory tree and can cause tracheitis, bronchitis, bronchiolitis, diffuse alveolar damage with pulmonary edema and hemorrhage, and interstitial and airspace inflammation. The mechanisms by which influenza infections result in enhanced disease, including development of pneumonia and acute respiratory distress, are multifactorial, involving host, viral, and bacterial factors. Host factors that enhance risk of severe influenza disease include underlying comorbidities, such as cardiac and respiratory disease, immunosuppression, and pregnancy. Viral parameters enhancing disease risk include polymerase mutations associated with host switch and adaptation, viral proteins that modulate immune and antiviral responses, and virulence factors that increase disease severity, which can be especially prominent in pandemic viruses and some zoonotic influenza viruses causing human infections. Influenza viral infections result in damage to the respiratory epithelium that facilitates secondary infection with common bacterial pneumopathogens and can lead to secondary bacterial pneumonias that greatly contribute to respiratory distress, enhanced morbidity, and death. Understanding the molecular mechanisms by which influenza and secondary bacterial infections, coupled with the role of host risk factors, contribute to enhanced morbidity and mortality is essential to develop better therapeutic strategies to treat severe influenza. C1 [Kash, John C.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 North Dr,Room 3E19A-2,MSC 3203, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, NIH, Intramural Research Program [1-ZIA-AI000986-08] FX Supported by the National Institute of Allergy and Infectious Diseases, NIH, Intramural Research Program grant 1-ZIA-AI000986-08. NR 73 TC 14 Z9 14 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2015 VL 185 IS 6 BP 1528 EP 1536 DI 10.1016/j.ajpath.2014.08.030 PG 9 WC Pathology SC Pathology GA CJ2YL UT WOS:000355350500004 PM 25747532 ER EF